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Clinical Trial Results:
Activity and safety of regorafenib in patients with metastatic. Soft tissue sarcoma previously treated with anthracyclin-based chemotherapy: a multinational, randomized, phase II, placebo-controlled trial

Summary
EudraCT number	2012-005743-24
Trial protocol	AT
Global end of trial date	11 Mar 2020

Results information
Results version number	v1(current)
This version publication date	07 Nov 2025
First version publication date	07 Nov 2025
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

REGO-SARC-1214

ISRCTN number

US NCT number

NCT01900743

WHO universal trial number (UTN)

Sponsor organisation name

Centre Oscar Lambret

Sponsor organisation address

3 rue Frédéric Combemale, Lille, France, 59000

Public contact

Project manager, Centre Oscar Lambret, 33 320295918, promotion@o-lambret.fr

Scientific contact

Project manager, Centre Oscar Lambret, 33 320295918, promotion@o-lambret.fr

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

11 Mar 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

11 Mar 2020

Global end of trial reached?

Yes

Global end of trial date

11 Mar 2020

Was the trial ended prematurely?

Main objective of the trial

Main objective: to investigate whether treatment with regorafenib improves the outcome of patients with metastatic soft tissue sarcoma, when compared with placebo. The primary endpoint was progression-free survival in the intention-to-treat population, according to RECIST (version 1.1) based on central radiological review.

Protection of trial subjects

The study was approved by an ethical and regulatory committee (French Ethical Committee [Comité de Protection des Patients Nord-Ouest IV; date of approval March 21, 2013], Austrian Ethical Committee [Ethik Kommission Medizinische Universität Wien; number 1376/2013], and the French and Austrian Drug Agencies [Agence Nationale de Sécurité du Médicament; date of approval March 8, 2013]). IDMC (23/05/2014) => In view of the acceptable tolerability data, consistent with that already known for regorafenib, and the encouraging preliminary activity data, the IDMC members recommend continuing the study. However, due to the number of deaths, the IDMC recommends particular vigilance with regard to toxicities and wishes to meet again at the end of the year to reassess tolerability

Background therapy

Evidence for comparator

Actual start date of recruitment

12 Jun 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 15

Country: Number of subjects enrolled

France: 203

Worldwide total number of subjects

218

EEA total number of subjects

218

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

143

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Overall, 218 pts included between 12/06/2013 and 19/10/2017, - placebo: n=111 - regorafenib: n=107 stratified in 5 cohorts -Cohort A: Liposarcoma -Cohort B: leiomyosarcoma -Cohort C: synovial sarcoma -Cohort D: other sarcoma -Cohort E: non-adipocytic patients previously treated with both chemotherapy and pazopanib

Screening details

One patient was included twice, his duplicate was deleted from the analysis.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Assessor

Blinding implementation details

Patients, investigators and radiologists were all blinded to treatment allocation. At the treating sites, only pharmacists were aware of the allocated treatment. Unblinding could be done by the sponsor on request of the investigator in case of emergency (safety issue), progression and need to know the treatment received to continue medical care, or for any reason justified by the investigator. A cross-over was authorized after confirmed progression.

Are arms mutually exclusive

Yes

Cohort A - Placebo arm

Arm description

Patients with liposarcoma and treatment by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Cohort A - Regorafenib arm

Arm description

Patients with liposarcoma and treatment by Regorafenib (160 mg, 4 tablets, once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Arm type

Experimental

Investigational medicinal product name

Regorafenib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Regorafenib: 4 tablets, once daily, 3 weeks on / 1 week off + Best Supportive Care

Cohort B -Placebo arm

Arm description

Patients with Leiomyosarcoma and treatment by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Cohort B - Regorafenib arm

Arm description

Patients with Leiomyosarcoma and treatment by Regorafenib (160 mg, 4 tablets, once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Arm type

Experimental

Investigational medicinal product name

Regorafenib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Regorafenib: 4 tablets, once daily, 3 weeks on / 1 week off + Best Supportive Care

Cohort C - Placebo arm

Arm description

Patients with synovial sarcoma and treatment by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Cohort C - Regorafenib arm

Arm description

Patients with synovial sarcoma and treatment by Regorafenib (160 mg, 4 tablets, once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Arm type

Experimental

Investigational medicinal product name

Regorafenib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Regorafenib: 4 tablets, once daily, 3 weeks on / 1 week off + Best Supportive Care

Cohort D -Placebo arm

Arm description

Patients with other sarcoma and treatment by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Cohort D -Regorafenib arm

Arm description

Patients with other sarcoma and treatment by Regorafenib (160 mg, 4 tablets, once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Arm type

Experimental

Investigational medicinal product name

Regorafenib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Regorafenib: 4 tablets, once daily, 3 weeks on / 1 week off + Best Supportive Care

Cohort E -Placebo arm

Arm description

Patients with metastatic non-adipocytic STS who were previously treated with both chemotherapy and pazopanib and treated by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Cohort E - Regorafenib arm

Arm description

Patients with metastatic non-adipocytic STS who were previously treated with both chemotherapy and pazopanib and treated by Regorafenib(160mg, 4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Arm type

Experimental

Investigational medicinal product name

Regorafenib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Regorafenib: 4 tablets, once daily, 3 weeks on / 1 week off + Best Supportive Care

Number of subjects in period 1	Cohort A - Placebo arm	Cohort A - Regorafenib arm	Cohort B -Placebo arm	Cohort B - Regorafenib arm	Cohort C - Placebo arm	Cohort C - Regorafenib arm	Cohort D -Placebo arm	Cohort D -Regorafenib arm	Cohort E -Placebo arm	Cohort E - Regorafenib arm
Started	23	20	28	28	14	13	27	28	19	18
Completed	23	20	28	28	14	13	27	28	19	18

Baseline characteristics

Top of page

Reporting group title

Cohort A - Placebo arm

Reporting group description

Patients with liposarcoma and treatment by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort A - Regorafenib arm

Reporting group description

Patients with liposarcoma and treatment by Regorafenib (160 mg, 4 tablets, once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort B -Placebo arm

Reporting group description

Patients with Leiomyosarcoma and treatment by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort B - Regorafenib arm

Reporting group description

Patients with Leiomyosarcoma and treatment by Regorafenib (160 mg, 4 tablets, once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort C - Placebo arm

Reporting group description

Patients with synovial sarcoma and treatment by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort C - Regorafenib arm

Reporting group description

Patients with synovial sarcoma and treatment by Regorafenib (160 mg, 4 tablets, once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort D -Placebo arm

Reporting group description

Patients with other sarcoma and treatment by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort D -Regorafenib arm

Reporting group description

Patients with other sarcoma and treatment by Regorafenib (160 mg, 4 tablets, once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort E -Placebo arm

Reporting group description

Reporting group title

Cohort E - Regorafenib arm

Reporting group description

Reporting group values	Cohort A - Placebo arm	Cohort A - Regorafenib arm	Cohort B -Placebo arm	Cohort B - Regorafenib arm	Cohort C - Placebo arm	Cohort C - Regorafenib arm	Cohort D -Placebo arm	Cohort D -Regorafenib arm	Cohort E -Placebo arm	Cohort E - Regorafenib arm	Total
Number of subjects	23	20	28	28	14	13	27	28	19	18	218
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	11	15	18	17	13	12	16	14	16	11	143
From 65-84 years	12	5	10	11	1	1	11	14	3	7	75
85 years and over	0	0	0	0	0	0	0	0	0	0	0
Age continuous
Units: years
median (full range (min-max))	65 (22 to 80)	57.5 (24 to 76)	60 (30 to 76)	60.5 (32 to 74)	35.5 (20 to 68)	46 (21 to 73)	55 (20 to 78)	62.5 (26 to 81)	60 (36 to 76)	61 (41 to 71)	-
Gender categorical
Units: Subjects
Female	9	8	21	19	5	5	8	15	14	14	118
Male	14	12	7	9	9	8	19	13	5	4	100
ECOG performance status
ECOG performance status
Units: Subjects
ECOG=0	10	10	13	12	9	7	13	11	8	9	102
ECOG=1	12	10	15	16	5	6	14	17	11	8	114
ECOG=2	1	0	0	0	0	0	0	0	0	0	1
Missing	0	0	0	0	0	0	0	0	0	1	1
Metastasis
Metastasis at inclusion
Units: Subjects
No	4	1	0	0	1	0	0	2	2	0	10
Yes	19	19	28	28	13	13	27	26	17	18	208
Histological subtype (definitive)
Histological subtype (definitive)
Units: Subjects
Liposarcoma	23	20	0	0	0	0	0	1	0	0	44
Leiomysarcoma	0	0	28	28	0	0	0	1	11	13	81
Synovial sarcoma	0	0	0	0	14	13	0	0	1	0	28
Other sarcoma	0	0	0	0	0	0	27	26	7	5	65
Histopronostic grade
Histopronostic grade
Units: Subjects
Grade 1	2	6	2	1	0	0	1	1	0	2	15
Grade 2	13	7	17	10	8	3	7	6	3	7	81
Grade 3	5	4	7	14	5	9	13	13	10	5	85
Missing	3	3	2	3	1	1	0	0	6	4	23
Not applicable	0	0	0	0	0	0	6	8	0	0	14

End points

Top of page

Reporting group title

Cohort A - Placebo arm

Reporting group description

Patients with liposarcoma and treatment by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort A - Regorafenib arm

Reporting group description

Patients with liposarcoma and treatment by Regorafenib (160 mg, 4 tablets, once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort B -Placebo arm

Reporting group description

Patients with Leiomyosarcoma and treatment by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort B - Regorafenib arm

Reporting group description

Patients with Leiomyosarcoma and treatment by Regorafenib (160 mg, 4 tablets, once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort C - Placebo arm

Reporting group description

Patients with synovial sarcoma and treatment by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort C - Regorafenib arm

Reporting group description

Patients with synovial sarcoma and treatment by Regorafenib (160 mg, 4 tablets, once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort D -Placebo arm

Reporting group description

Patients with other sarcoma and treatment by placebo (4 tablets once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort D -Regorafenib arm

Reporting group description

Patients with other sarcoma and treatment by Regorafenib (160 mg, 4 tablets, once daily, 3 weeks on / 1 week off plus Best Supportive Care)

Reporting group title

Cohort E -Placebo arm

Reporting group description

Reporting group title

Cohort E - Regorafenib arm

Reporting group description

Primary: Progression-free survival - cohort A

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End point title

Progression-free survival - cohort A ^[1]

End point description

Progression-Free Survival measured from the date of randomization until the date of radiological progression or death whatever the cause (if death occurs before progression). Patients without tumor progression or death at the time of analysis censored at their last date of radiological tumor assessment. The date of disease of progression was the date of first observation of progression (primary analysis on intent-to-treat analysis, according to RECIST 1.1 guidelines).

End point type

Primary

End point timeframe

Tumor evaluation was planned every 1 month during the first 4 months, at 6 months and then every 3 months.

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort A - Placebo arm	Cohort A - Regorafenib arm
Number of subjects analysed	23	20
Units: Survival estimate (%)
number (confidence interval 95%)
At 3 months	26 (10 to 44)	25 (9 to 45)
At 6 months	8 (1 to 24)	20 (6 to 39)
At 9 months	8 (1 to 24)	5 (0 to 20)

Progression free survival

Statistical analysis description

Cox model were used to estimate the hazard ratios (HR) and 95% confidence intervals (95%CI) associated with the treatmeant effect (regorafenib versus placebo) after testing the proportional hazards assumption, using the scaled Schoenfeld residuals method

Comparison groups

Cohort A - Regorafenib arm v Cohort A - Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[2]

P-value

= 0.7

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

1.64

Notes
[2] - Effect of treatment (Regorafenib versus placebo) Cox model

Primary: Progression-free survival - cohort B

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End point title

Progression-free survival - cohort B ^[3]

End point description

End point type

Primary

End point timeframe

Tumor evaluation was planned every 1 month during the first 4 months, at 6 months and then every 3 months Based on data from a complete review carried out in 2021

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort B -Placebo arm	Cohort B - Regorafenib arm
Number of subjects analysed	28	28
Units: Survival estimate (%)
number (confidence interval 95%)
At 3 months	11.6 (3.0 to 26.8)	21.4 (8.7 to 37.8)
At 6 months	7.7 (1.4 to 21.8)	7.1 (1.3 to 20.4)
At 12 months	3.9 (0.3 to 16.5)	3.6 (0.3 to 15.4)

Progression free survival - adjusted HR

Statistical analysis description

Comparison groups

Cohort B - Regorafenib arm v Cohort B -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[4]

P-value

= 0.21

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

1.21

Notes
[4] - Effect of treatment (Regorafenib versus placebo) Cox model: Adjusted HR (IC95%) HR adjusted on stratification factors (Country: France versus Austria; prior exposure to pazopanib: Yes vs no)

Progression free survival - not adjusted HR

Statistical analysis description

Comparison groups

Cohort B - Regorafenib arm v Cohort B -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

= 0.21

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.42

upper limit

1.22

Notes
[5] - Effect of treatment (Regorafenib versus placebo) Cox model: not adjusted HR (IC95%)

Primary: Progression-free survival - cohort C

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End point title

Progression-free survival - cohort C ^[6]

End point description

End point type

Primary

End point timeframe

Tumor evaluation was planned every 1 month during the first 4 months, at 6 months and then every 3 months Based on data from a complete review carried out in 2021

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort C - Placebo arm	Cohort C - Regorafenib arm
Number of subjects analysed	14	13
Units: Survival estimate (%)
number (confidence interval 95%)
At 3 months	0 (0 to 0)	42.3 (15.6 to 67.1)
At 6 months	0 (0 to 0)	21.2 (3.6 to 48.4)
At 12 months	0 (0 to 0)	0 (0 to 0)

Progression free survival - adjusted HR

Statistical analysis description

Comparison groups

Cohort C - Regorafenib arm v Cohort C - Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[7]

P-value

= 0.001

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.04

upper limit

0.46

Notes
[7] - Effect of treatment (Regorafenib versus placebo) Cox model: Adjusted HR (IC95%) HR adjusted on stratification factors (Country: France versus Austria; prior exposure to pazopanib: Yes vs no)

Progression free survival - not adjusted H

Statistical analysis description

Comparison groups

Cohort C - Regorafenib arm v Cohort C - Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[8]

P-value

= 0.001

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

0.45

Notes
[8] - Effect of treatment (Regorafenib versus placebo) Cox model: not adjusted HR (IC95%)

Primary: Progression-free survival - cohort D

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End point title

Progression-free survival - cohort D ^[9]

End point description

End point type

Primary

End point timeframe

Tumor evaluation was planned every 1 month during the first 4 months, at 6 months and then every 3 months Based on data from a complete review carried out in 2021

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort D -Placebo arm	Cohort D -Regorafenib arm
Number of subjects analysed	27	28
Units: Survival estimate (%)
number (confidence interval 95%)
At 3 months	10.0 (2.0 to 25.3)	46.4 (27.6 to 63.3)
At 6 months	4.9 (0.4 to 19.5)	16.9 (5.4 to 33.7)
At 12 months	4.9 (0.4 to 19.5)	4.2 (0.3 to 17.7)

Progression free survival - adjusted HR

Statistical analysis description

Cox models were used to estimate the hazard ratios (HR) and 95% confidence intervals (95%CI) associated with the treatmeant effect (regorafenib versus placebo) after testing the proportional hazards assumption, using the scaled Schoenfeld residuals method

Comparison groups

Cohort D -Regorafenib arm v Cohort D -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[10]

P-value

= 0.03

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.29

upper limit

0.95

Notes
[10] - Effect of treatment (Regorafenib versus placebo) Cox model: Adjusted HR (IC95%) HR adjusted on stratification factors (Country: France versus Austria; prior exposure to pazopanib: Yes vs no)

Progression free survival - not adjusted HR

Statistical analysis description

Comparison groups

Cohort D -Regorafenib arm v Cohort D -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[11]

P-value

= 0.03

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.3

upper limit

0.94

Notes
[11] - Effect of treatment (Regorafenib versus placebo) Cox model: not adjusted HR (IC95%)

Primary: Progression-free survival - cohort E

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End point title

Progression-free survival - cohort E ^[12]

End point description

End point type

Primary

End point timeframe

Tumor evaluation was planned every 1 month during the first 4 months, at 6 months and then every 3 months. Based on data from a complete review carried out in 2021

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort E -Placebo arm	Cohort E - Regorafenib arm
Number of subjects analysed	19	18
Units: Survival estimate (%)
number (confidence interval 95%)
At 3 months	5 (0 to 21)	33 (14 to 54)
At 6 months	0 (0 to 0)	22 (7 to 43)
At 12 months	0 (0 to 0)	6 (0 to 22)

Progression free survival - adjusted HR

Statistical analysis description

Comparison groups

Cohort E - Regorafenib arm v Cohort E -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[13]

P-value

= 0.007

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.15

upper limit

0.74

Notes
[13] - Analysis: model adjusted for histology (leiomyosarcoma vs. other sarcoma, one patient with synovial sarcoma was considered as other sarcoma for this analysis), number of prior lines of systemic treatment (<4 vs. 4+).

Progression free survival - not adjusted HR

Statistical analysis description

Comparison groups

Cohort E - Regorafenib arm v Cohort E -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[14]

P-value

= 0.0023

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.31

Confidence interval

level

95%

sides

2-sided

lower limit

0.15

upper limit

0.67

Notes
[14] - Effect of treatment (Regorafenib versus placebo) Cox model: not adjusted HR (IC95%)

Progression free survival - Post-hoc adjusted HR

Statistical analysis description

Comparison groups

Cohort E - Regorafenib arm v Cohort E -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[15]

P-value

= 0.12

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.39

Confidence interval

level

95%

sides

2-sided

lower limit

0.12

upper limit

1.28

Notes
[15] - Post-hoc analysis: model adjusted for histology (Leiomyosarcoma vs. other sarcoma, one patient with synovial sarcoma was considered as other sarcoma for this analysis), number of prior lines of systemic treatment (<4 vs. 4+) and histological grade (I and II vs III). Ten cases are excluded in this analysis because of missing data for the grade: six in placebo arm and four in regorafenib arm.

Secondary: Overall Survival - cohort A

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End point title

Overall Survival - cohort A ^[16]

End point description

OS, defined as the time interval from the date of randomisation to the date of death from any cause. In each group, the OS curve was estimated using the Kaplan-Meier method

End point type

Secondary

End point timeframe

Until the end of the study

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort A - Placebo arm	Cohort A - Regorafenib arm
Number of subjects analysed	23	20
Units: Survival estimate (%)
number (confidence interval 95%)
At 3 months	91.3 (69.5 to 97.6)	73.9 (48.2 to 88.2)
At 6 months	77.6 (54.3 to 90.0)	42.2 (20.5 to 62.6)

Overall survival - not adjusted HR

Statistical analysis description

Cox model were used to estimate the hazard ratios (HR) and 95% confidence intervals (95%CI) associated with the treatment effect (regorafenib versus placebo) after testing the proportional hazards assumption, using the scaled Schoenfeld residuals method

Comparison groups

Cohort A - Regorafenib arm v Cohort A - Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[17]

P-value

= 0.21

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

1.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.77

upper limit

3.21

Notes
[17] - Effect of treatment (Regorafenib versus placebo) Cox model: not ajusted HR (IC95%)

Secondary: Overall Survival - cohort B

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End point title

Overall Survival - cohort B ^[18]

End point description

OS, defined as the time interval from the date of randomisation to the date of death from any cause. In each group, the OS curve was estimated using the Kaplan-Meier method

End point type

Secondary

End point timeframe

Until the end of the study

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort B -Placebo arm	Cohort B - Regorafenib arm
Number of subjects analysed	28	28
Units: Survival estimate (%)
number (confidence interval 95%)
At 3 months	92.9 (74.4 to 98.2)	92.9 (74.4 to 98.2)
At 6 months	78.6 (58.4 to 89.8)	78.6 (58.4 to 89.8)
At 12 months	46.4 (27.6 to 63.3)	60.7 (40.4 to 76.0)

Overall survival - adjusted HR

Statistical analysis description

Cox models were used to estimate the hazard ratios (HR) and 95% confidence intervals (95%CI) associated with the treatment effect (regorafenib versus placebo) after testing the proportional hazards assumption, using the scaled Schoenfeld residuals method

Comparison groups

Cohort B - Regorafenib arm v Cohort B -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[19]

P-value

= 0.15

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.67

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

1.15

Notes
[19] - Effect of treatment (Regorafenib versus placebo) Cox model: adjusted HR (IC95%) HR - Adjusted on stratification factors (Country: France versus Austria; prior exposure to pazopanib: Yes vs no)

Overall survival - not adjusted HR

Statistical analysis description

Comparison groups

Cohort B - Regorafenib arm v Cohort B -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[20]

P-value

= 0.17

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

1.18

Notes
[20] - Effect of treatment (Regorafenib versus placebo) Cox model: not adjusted HR (IC95%)

Secondary: Best tumor response, according to full central review -Cohort B

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End point title

Best tumor response, according to full central review -Cohort B ^[21]

End point description

End point type

Secondary

End point timeframe

Best tumor response, according to full central review (and clinical information if applicable) – by treatment arm (cohort B)

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort B -Placebo arm	Cohort B - Regorafenib arm
Number of subjects analysed	28	28
Units: Best response
number (not applicable)
Complete response	0	0
Partial response	0	0
Stable disease	12	17
Progressive disease	16	11

No statistical analyses for this end point

Secondary: Overall Survival - cohort C

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End point title

Overall Survival - cohort C ^[22]

End point description

OS, defined as the time interval from the date of randomisation to the date of death from any cause. In each group, the OS curve was estimated using the Kaplan-Meier method

End point type

Secondary

End point timeframe

Until the end of the study

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort C - Placebo arm	Cohort C - Regorafenib arm
Number of subjects analysed	14	13
Units: Survival estimate (%)
number (confidence interval 95%)
At 3 months	85.7 (53.9 to 96.2)	92.3 (56.6 to 98.9)
At 6 months	64.3 (34.3 to 83.3)	76.9 (44.2 to 91.9)
At 12 months	35.7 (13.0 to 59.4)	61.5 (30.8 to 81.8)

Overall survival - adjusted HR

Statistical analysis description

Comparison groups

Cohort C - Regorafenib arm v Cohort C - Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[23]

P-value

= 0.78

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.89

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

2.01

Notes
[23] - Effect of treatment (Regorafenib versus placebo) Cox model: adjusted HR (IC95%) HR - Adjusted on stratification factors (Country: France versus Austria; prior exposure to pazopanib: Yes vs no)

Overall survival - not adjusted HR

Statistical analysis description

Comparison groups

Cohort C - Regorafenib arm v Cohort C - Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[24]

P-value

= 0.94

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.44

upper limit

2.13

Notes
[24] - Effect of treatment (Regorafenib versus placebo) Cox model: not adjusted HR (IC95%)

Secondary: Best tumor response, according to full central review -Cohort C

Top of page

End point title

Best tumor response, according to full central review -Cohort C ^[25]

End point description

End point type

Secondary

End point timeframe

Best tumor response, according to full central review (and clinical information if applicable) – by treatment arm (cohort C)

Notes
[25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort C - Placebo arm	Cohort C - Regorafenib arm
Number of subjects analysed	14	12 ^[26]
Units: Best response
number (not applicable)
Complete response	0	0
Partial response	0	0
Stable disease	3	8
Progressive disease	11	4

Notes
[26] - One patient had no central review due to issue in quality control

No statistical analyses for this end point

Secondary: Overall Survival - cohort D

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End point title

Overall Survival - cohort D ^[27]

End point description

OS, defined as the time interval from the date of randomisation to the date of death from any cause. In each group, the OS curve was estimated using the Kaplan-Meier method

End point type

Secondary

End point timeframe

Until the end of the study

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort D -Placebo arm	Cohort D -Regorafenib arm
Number of subjects analysed	27	28
Units: Survival estimate (%)
number (confidence interval 95%)
At 3 months	77.8 (57.1 to 89.3)	82.1 (62.3 to 92.2)
At 6 months	66.7 (45.7 to 81.1)	75.0 (54.6 to 87.2)
At 12 months	37.0 (19.6 to 54.6)	53.6 (33.8 to 69.8)

Overall survival - adjusted HR

Statistical analysis description

Comparison groups

Cohort D -Regorafenib arm v Cohort D -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[28]

P-value

= 0.91

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.97

Confidence interval

level

95%

sides

2-sided

lower limit

0.55

upper limit

1.7

Notes
[28] - Effect of treatment (Regorafenib versus placebo) Cox model: adjusted HR (IC95%) HR - Adjusted on stratification factors (Country: France versus Austria; prior exposure to pazopanib: Yes vs no)

Overall survival - not adjusted HR

Statistical analysis description

Comparison groups

Cohort D -Regorafenib arm v Cohort D -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[29]

P-value

= 0.82

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.94

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

1.63

Notes
[29] - Effect of treatment (Regorafenib versus placebo) Cox model: not adjusted HR (IC95%)

Secondary: Best tumor response, according to full central review -Cohort D

Top of page

End point title

Best tumor response, according to full central review -Cohort D ^[30]

End point description

End point type

Secondary

End point timeframe

Best tumor response, according to full central review (and clinical information if applicable) – by treatment arm (cohort D)

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort D -Placebo arm	Cohort D -Regorafenib arm
Number of subjects analysed	27	26 ^[31]
Units: Best response
number (not applicable)
Complete response	0	0
Partial response	0	1
Stable disease	9	12
Progressive disease	18	13

Notes
[31] - 2 patients had no central review due to issue in quality control

No statistical analyses for this end point

Secondary: Overall Survival - cohort E

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End point title

Overall Survival - cohort E ^[32]

End point description

OS, defined as the time interval from the date of randomisation to the date of death from any cause. In each group, the OS curve was estimated using the Kaplan-Meier method

End point type

Secondary

End point timeframe

Until the end of the study

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort E -Placebo arm	Cohort E - Regorafenib arm
Number of subjects analysed	19	18
Units: Survival estimate (%)
number (confidence interval 95%)
At 3 months	89 (64 to 97)	88 (61 to 97)
At 6 months	79 (53 to 91)	83 (55 to 94)
At 12 months	37 (16 to 57)	65 (38 to 82)

Overall survival - adjusted HR

Statistical analysis description

Comparison groups

Cohort E - Regorafenib arm v Cohort E -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[33]

P-value

= 0.07

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.49

Confidence interval

level

95%

sides

2-sided

lower limit

0.23

upper limit

1.06

Notes
[33] - Analysis: model adjusted for histology (leiomyosarcoma vs. other sarcoma, one patient with synovial sarcoma was considered as other sarcoma for this analysis), number of prior lines of systemic treatment (<4 vs. 4+).

Overall survival - not adjusted HR

Statistical analysis description

Comparison groups

Cohort E - Regorafenib arm v Cohort E -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[34]

P-value

= 0.058

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.49

Confidence interval

level

95%

sides

2-sided

lower limit

0.23

upper limit

1.03

Notes
[34] - Effect of treatment (Regorafenib versus placebo) Cox model: not adjusted HR (IC95%)

Overall survival - Post-hoc adjusted HR

Statistical analysis description

Comparison groups

Cohort E - Regorafenib arm v Cohort E -Placebo arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[35]

P-value

= 0.09

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.37

Confidence interval

level

95%

sides

2-sided

lower limit

0.11

upper limit

1.17

Notes
[35] - Post-hoc analysis: model adjusted for histology (Leiomyosarcoma vs. other sarcoma, one patient with synovial sarcoma was considered as other sarcoma for this analysis), number of prior lines of systemic treatment (<4 vs. 4+) and histological grade (I and II vs III). Ten cases are excluded in this analysis because of missing data for the grade: six in placebo arm and four in regorafenib arm.

Secondary: Best tumor response, according to full central review -Cohort E

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End point title

Best tumor response, according to full central review -Cohort E ^[36]

End point description

End point type

Secondary

End point timeframe

Best tumor response, according to full central review (and clinical information if applicable) – by treatment arm (cohort E)

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The results provided are results by cohort and treatment group.

End point values	Cohort E -Placebo arm	Cohort E - Regorafenib arm
Number of subjects analysed	19	18
Units: Best response
number (not applicable)
Complete response	0	0
Partial response	0	0
Stable disease	8	13
Progressive disease	11	5

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Safety was evaluated during the whole treatment duration up to the visit performed 30 (+/- 7) days after permanent treatment discontinuation.

Adverse event reporting additional description

AE additional description AEs are detailed by treatment group: regorafenib versus placebo across all cohorts combined.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

Regorafenib arm

Reporting group description

Reporting group title

Placebo arm

Reporting group description

Serious adverse events	Regorafenib arm	Placebo arm
Total subjects affected by serious adverse events
subjects affected / exposed	52 / 107 (48.60%)	21 / 111 (18.92%)
number of deaths (all causes)	102	109
number of deaths resulting from adverse events	6	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
Additional description: Malignant neoplasm progression
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tumor pain
Additional description: Tumor pain
subjects affected / exposed	5 / 107 (4.67%)	2 / 111 (1.80%)
occurrences causally related to treatment / all	1 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Arterial hypertension
Additional description: Arterial hypertension
subjects affected / exposed	3 / 107 (2.80%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypotension
Additional description: Hypotension
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
Additional description: Pulmonary embolism
subjects affected / exposed	1 / 107 (0.93%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tumor hemorrhage
Additional description: Tumor hemorrhage
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Neurosurgery
Additional description: Neurosurgery
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Surgery
Additional description: Surgery
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Anorexia
Additional description: Anorexia
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Asthenia
Additional description: Asthenia
subjects affected / exposed	2 / 107 (1.87%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	1 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fever
Additional description: Fever
subjects affected / exposed	5 / 107 (4.67%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	3 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General physical health deterioration
Additional description: General physical health deterioration
subjects affected / exposed	6 / 107 (5.61%)	4 / 111 (3.60%)
occurrences causally related to treatment / all	0 / 6	0 / 4
deaths causally related to treatment / all	0 / 2	0 / 3
Pain
Additional description: Pain
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Pelvic pain
Additional description: Pelvic pain
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
Additional description: Acute respiratory distress syndrome
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Aspiration
Additional description: Aspiration
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspnoea
Additional description: Dyspnoea
subjects affected / exposed	3 / 107 (2.80%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hemothorax
Additional description: Hemothorax
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax
Additional description: Pneumothorax
subjects affected / exposed	2 / 107 (1.87%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Pleural effusion
Additional description: Pleural effusion
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Respiratory failure
Additional description: Respiratory failure
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Respiratory distress
Additional description: Respiratory distress
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Investigations
Hypercalcemia
Additional description: Hypercalcemia
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperglycemia
Additional description: Hyperglycemia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoglycemia
Additional description: Hypoglycemia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Acetabulum fracture
Additional description: Acetabulum fracture
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Postoperative wound complication
Additional description: Postoperative wound complication
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Cardiac arrest
Additional description: Cardiac arrest
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure
Additional description: Cardiac failure
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chest pain
Additional description: Chest pain
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial ischaemia
Additional description: Myocardial ischaemia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tachycardia
Additional description: Tachycardia
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Encephalopathy
Additional description: Encephalopathy
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Headache
Additional description: Headache
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Motor dysfunction
Additional description: Motor dysfunction
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vertigo
Additional description: Vertigo
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anemia
Additional description: Anemia
subjects affected / exposed	2 / 107 (1.87%)	3 / 111 (2.70%)
occurrences causally related to treatment / all	2 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
Additional description: Abdominal pain
subjects affected / exposed	4 / 107 (3.74%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Ascites
Additional description: Ascites
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
Additional description: Diarrhoea
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric perforation
Additional description: Gastric perforation
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal fistula
Additional description: Gastrointestinal fistula
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal perforation
Additional description: Gastrointestinal perforation
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hernial eventration
Additional description: Hernial eventration
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal perforation
Additional description: Intestinal perforation
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophagitis
Additional description: Oesophagitis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nausea
Additional description: Nausea
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subileus
Additional description: Subileus
subjects affected / exposed	1 / 107 (0.93%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
Additional description: Vomiting
subjects affected / exposed	3 / 107 (2.80%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
Additional description: Cholecystitis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatocellular injury
Additional description: Hepatocellular injury
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0
Jaundice
Additional description: Jaundice
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis allergic
Additional description: Dermatitis allergic
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin toxicity
Additional description: Skin toxicity
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin exfoliation
Additional description: Skin exfoliation
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rash
Additional description: Rash
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Urinary retention
Additional description: Urinary retention
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Hyperthyroidism
Additional description: Hyperthyroidism
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
Additional description: Back pain
subjects affected / exposed	1 / 107 (0.93%)	2 / 111 (1.80%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Flank pain
Additional description: Flank pain
subjects affected / exposed	1 / 107 (0.93%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pain in extremity
Additional description: Pain in extremity
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Device related infection
Additional description: Device related infection
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster
Additional description: Herpes zoster
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis
Additional description: Pyelonephritis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
Additional description: Pneumonia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Peritonitis
Additional description: Peritonitis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal infection
Additional description: Staphylococcal infection
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Regorafenib arm	Placebo arm
Total subjects affected by non serious adverse events
subjects affected / exposed	107 / 107 (100.00%)	105 / 111 (94.59%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
Additional description: Skin papilloma
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Tumor pain
Additional description: Tumor pain
subjects affected / exposed	5 / 107 (4.67%)	3 / 111 (2.70%)
occurrences all number	5	3
Vascular disorders
Anal hemorrhage
Additional description: Anal hemorrhage
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Arterial hypertension
Additional description: Arterial hypertension
subjects affected / exposed	32 / 107 (29.91%)	5 / 111 (4.50%)
occurrences all number	46	6
Ecchymosis
Additional description: Ecchymosis
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Epistaxis
Additional description: Epistaxis
subjects affected / exposed	11 / 107 (10.28%)	3 / 111 (2.70%)
occurrences all number	20	3
Flushing
Additional description: Flushing
subjects affected / exposed	2 / 107 (1.87%)	1 / 111 (0.90%)
occurrences all number	2	1
Haematoma
Additional description: Haematoma
subjects affected / exposed	1 / 107 (0.93%)	2 / 111 (1.80%)
occurrences all number	1	2
Hematuria
Additional description: Hematuria
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	2	0
Hemoptysis
Additional description: Hemoptysis
subjects affected / exposed	6 / 107 (5.61%)	2 / 111 (1.80%)
occurrences all number	11	3
Hemorrhage
Additional description: Hemorrhage
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Hypertensive crisis
Additional description: Hypertensive crisis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Hypotension
Additional description: Hypotension
subjects affected / exposed	4 / 107 (3.74%)	3 / 111 (2.70%)
occurrences all number	4	3
Metrorrhagia
Additional description: Metrorrhagia
subjects affected / exposed	2 / 107 (1.87%)	1 / 111 (0.90%)
occurrences all number	3	1
Mouth hemorrhage
Additional description: Mouth hemorrhage
subjects affected / exposed	2 / 107 (1.87%)	1 / 111 (0.90%)
occurrences all number	2	2
Thrombosis
Additional description: Thrombosis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Thrombophlebitis
Additional description: Thrombophlebitis
subjects affected / exposed	0 / 107 (0.00%)	2 / 111 (1.80%)
occurrences all number	0	2
Superior vena cava syndrome
Additional description: Superior vena cava syndrome
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Rectal hemorrhage
Additional description: Rectal hemorrhage
subjects affected / exposed	2 / 107 (1.87%)	1 / 111 (0.90%)
occurrences all number	2	1
Surgical and medical procedures
Cataract operation
Additional description: Cataract operation
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
General disorders and administration site conditions
Anorexia
Additional description: Anorexia
subjects affected / exposed	44 / 107 (41.12%)	23 / 111 (20.72%)
occurrences all number	49	25
Appetite disorder
Additional description: Appetite disorder
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Asthenia
Additional description: Asthenia
subjects affected / exposed	72 / 107 (67.29%)	46 / 111 (41.44%)
occurrences all number	107	55
Cachexia
Additional description: Cachexia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Chills
Additional description: Chills
subjects affected / exposed	4 / 107 (3.74%)	1 / 111 (0.90%)
occurrences all number	4	1
Discomfort
Additional description: Discomfort
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Edema peripheral
Additional description: Edema peripheral
subjects affected / exposed	7 / 107 (6.54%)	7 / 111 (6.31%)
occurrences all number	9	7
Effusion
Additional description: Effusion
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Face edema
Additional description: Face edema
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Fever
Additional description: Fever
subjects affected / exposed	18 / 107 (16.82%)	6 / 111 (5.41%)
occurrences all number	37	6
General physical health deterioration
Additional description: General physical health deterioration
subjects affected / exposed	3 / 107 (2.80%)	2 / 111 (1.80%)
occurrences all number	3	2
Influenza like illness
Additional description: Influenza like illness
subjects affected / exposed	4 / 107 (3.74%)	3 / 111 (2.70%)
occurrences all number	4	3
Local swelling
Additional description: Local swelling
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Malaise
Additional description: Malaise
subjects affected / exposed	3 / 107 (2.80%)	0 / 111 (0.00%)
occurrences all number	3	0
Mucosal dryness
Additional description: Mucosal dryness
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Pain
Additional description: Pain
subjects affected / exposed	3 / 107 (2.80%)	3 / 111 (2.70%)
occurrences all number	3	3
Weight loss
Additional description: Weight loss
subjects affected / exposed	26 / 107 (24.30%)	10 / 111 (9.01%)
occurrences all number	26	10
Immune system disorders
Seasonal allergy
Additional description: Seasonal allergy
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Reproductive system and breast disorders
Amenorrhoea
Additional description: Amenorrhoea
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	2	0
Breast pain
Additional description: Breast pain
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Gynaecomastia
Additional description: Gynaecomastia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Pelvic pain
Additional description: Pelvic pain
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Phimosis
Additional description: Phimosis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	2	0
Vaginal inflammation
Additional description: Vaginal inflammation
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Vulvovaginal burning sensation
Additional description: Vulvovaginal burning sensation
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Respiratory, thoracic and mediastinal disorders
Atelectasis
Additional description: Atelectasis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Cough
Additional description: Cough
subjects affected / exposed	13 / 107 (12.15%)	10 / 111 (9.01%)
occurrences all number	14	10
Dysphonia
Additional description: Dysphonia
subjects affected / exposed	26 / 107 (24.30%)	2 / 111 (1.80%)
occurrences all number	27	2
Dyspnoea
Additional description: Dyspnoea
subjects affected / exposed	22 / 107 (20.56%)	15 / 111 (13.51%)
occurrences all number	23	17
Lower respiratory tract congestion
Additional description: Lower respiratory tract congestion
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Lung disorder
Additional description: Lung disorder
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Nasal discomfort
Additional description: Nasal discomfort
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Oropharyngeal pain
Additional description: Oropharyngeal pain
subjects affected / exposed	5 / 107 (4.67%)	1 / 111 (0.90%)
occurrences all number	7	1
Pleural effusion
Additional description: Pleural effusion
subjects affected / exposed	4 / 107 (3.74%)	2 / 111 (1.80%)
occurrences all number	4	2
Pneumonitis
Additional description: Pneumonitis
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Rhinorrhoea
Additional description: Rhinorrhoea
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Psychiatric disorders
Anxiety
Additional description: Anxiety
subjects affected / exposed	11 / 107 (10.28%)	3 / 111 (2.70%)
occurrences all number	11	3
Confusional state
Additional description: Confusional state
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Depression
Additional description: Depression
subjects affected / exposed	1 / 107 (0.93%)	1 / 111 (0.90%)
occurrences all number	1	1
Depressive symptom
Additional description: Depressive symptom
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Insomnia
Additional description: Insomnia
subjects affected / exposed	4 / 107 (3.74%)	5 / 111 (4.50%)
occurrences all number	4	5
Libido decreased
Additional description: Libido decreased
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Mental disorder
Additional description: Mental disorder
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Sleep disorder
Additional description: Sleep disorder
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Investigations
Blood alkaline phosphatase increased
Additional description: Blood alkaline phosphatase increased
subjects affected / exposed	51 / 107 (47.66%)	45 / 111 (40.54%)
occurrences all number	117	79
Blood chloride decreased
Additional description: Blood chloride decreased
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Blood lactate dehydrogenase increased
Additional description: Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 107 (0.00%)	3 / 111 (2.70%)
occurrences all number	0	3
Blood uric acid increased
Additional description: Blood uric acid increased
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Gamma-glutamyltransferase increased
Additional description: Gamma-glutamyltransferase increased
subjects affected / exposed	5 / 107 (4.67%)	8 / 111 (7.21%)
occurrences all number	8	8
Hypoglycemia
Additional description: Hypoglycemia
subjects affected / exposed	13 / 107 (12.15%)	5 / 111 (4.50%)
occurrences all number	23	8
Hyperamylasemia
Additional description: Hyperamylasemia
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	2	0
Hypercalcemia
Additional description: Hypercalcemia
subjects affected / exposed	8 / 107 (7.48%)	11 / 111 (9.91%)
occurrences all number	9	15
Hypercreatininemia
Additional description: Hypercreatininemia
subjects affected / exposed	24 / 107 (22.43%)	37 / 111 (33.33%)
occurrences all number	86	98
Hyperglycemia
Additional description: Hyperglycemia
subjects affected / exposed	48 / 107 (44.86%)	37 / 111 (33.33%)
occurrences all number	101	64
Hyperkalemia
Additional description: Hyperkalemia
subjects affected / exposed	11 / 107 (10.28%)	8 / 111 (7.21%)
occurrences all number	23	14
Hyperlipasemia
Additional description: Hyperlipasemia
subjects affected / exposed	12 / 107 (11.21%)	1 / 111 (0.90%)
occurrences all number	12	1
Hypernatraemia
Additional description: Hypernatraemia
subjects affected / exposed	1 / 107 (0.93%)	1 / 111 (0.90%)
occurrences all number	1	1
Hypertriglyceridemia
Additional description: Hypertriglyceridemia
subjects affected / exposed	3 / 107 (2.80%)	1 / 111 (0.90%)
occurrences all number	4	1
Hypoalbuminemia
Additional description: Hypoalbuminemia
subjects affected / exposed	48 / 107 (44.86%)	34 / 111 (30.63%)
occurrences all number	152	69
Hypocalcemia
Additional description: Hypocalcemia
subjects affected / exposed	39 / 107 (36.45%)	8 / 111 (7.21%)
occurrences all number	70	15
Hypokalemia
Additional description: Hypokalemia
subjects affected / exposed	26 / 107 (24.30%)	9 / 111 (8.11%)
occurrences all number	63	10
Hypophosphatemia
Additional description: Hypophosphatemia
subjects affected / exposed	34 / 107 (31.78%)	6 / 111 (5.41%)
occurrences all number	51	8
Hypovolaemia
Additional description: Hypovolaemia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Iron deficiency
Additional description: Iron deficiency
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Hyponatremia
Additional description: Hyponatremia
subjects affected / exposed	36 / 107 (33.64%)	32 / 111 (28.83%)
occurrences all number	85	39
Injury, poisoning and procedural complications
Contusion
Additional description: Contusion
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	2	0
Eschar
Additional description: Eschar
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Fall
Additional description: Fall
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	2	0
Hand fracture
Additional description: Hand fracture
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Rib fracture
Additional description: Rib fracture
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Cardiac disorders
Arrhythmia
Additional description: Arrhythmia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Atrial fibrillation
Additional description: Atrial fibrillation
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Chest pain
Additional description: Chest pain
subjects affected / exposed	10 / 107 (9.35%)	4 / 111 (3.60%)
occurrences all number	10	4
Ejection fraction decreased
Additional description: Ejection fraction decreased
subjects affected / exposed	1 / 107 (0.93%)	1 / 111 (0.90%)
occurrences all number	1	1
Palpitations
Additional description: Palpitations
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Tachycardia
Additional description: Tachycardia
subjects affected / exposed	3 / 107 (2.80%)	2 / 111 (1.80%)
occurrences all number	3	2
Ventricular hypokinesia
Additional description: Ventricular hypokinesia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Nervous system disorders
Dysaesthesia
Additional description: Dysaesthesia
subjects affected / exposed	2 / 107 (1.87%)	1 / 111 (0.90%)
occurrences all number	2	1
Dysarthria
Additional description: Dysarthria
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Headache
Additional description: Headache
subjects affected / exposed	24 / 107 (22.43%)	11 / 111 (9.91%)
occurrences all number	36	12
Hyperaesthesia
Additional description: Hyperaesthesia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Hypoaesthesia
Additional description: Hypoaesthesia
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Memory impairment
Additional description: Memory impairment
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Motor dysfunction
Additional description: Motor dysfunction
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Paraesthesia
Additional description: Paraesthesia
subjects affected / exposed	7 / 107 (6.54%)	3 / 111 (2.70%)
occurrences all number	9	5
Paraplegia
Additional description: Paraplegia
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Neuralgia
Additional description: Neuralgia
subjects affected / exposed	1 / 107 (0.93%)	2 / 111 (1.80%)
occurrences all number	1	2
Somnolence
Additional description: Somnolence
subjects affected / exposed	2 / 107 (1.87%)	1 / 111 (0.90%)
occurrences all number	2	1
Sciatica
Additional description: Sciatica
subjects affected / exposed	4 / 107 (3.74%)	1 / 111 (0.90%)
occurrences all number	4	1
Vertigo
Additional description: Vertigo
subjects affected / exposed	6 / 107 (5.61%)	0 / 111 (0.00%)
occurrences all number	6	0
Tremor
Additional description: Tremor
subjects affected / exposed	4 / 107 (3.74%)	0 / 111 (0.00%)
occurrences all number	4	0
Blood and lymphatic system disorders
Anemia
Additional description: Anemia
subjects affected / exposed	104 / 107 (97.20%)	103 / 111 (92.79%)
occurrences all number	597	289
Leukocytosis
Additional description: Leukocytosis
subjects affected / exposed	0 / 107 (0.00%)	2 / 111 (1.80%)
occurrences all number	0	2
Leukopenia
Additional description: Leukopenia
subjects affected / exposed	104 / 107 (97.20%)	103 / 111 (92.79%)
occurrences all number	584	276
Lymphopenia
Additional description: Lymphopenia
subjects affected / exposed	87 / 107 (81.31%)	85 / 111 (76.58%)
occurrences all number	437	204
Platelet count increased
Additional description: Platelet count increased
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Neutropenia
Additional description: Neutropenia
subjects affected / exposed	9 / 107 (8.41%)	3 / 111 (2.70%)
occurrences all number	20	5
Thrombocytopenia
Additional description: Thrombocytopenia
subjects affected / exposed	33 / 107 (30.84%)	8 / 111 (7.21%)
occurrences all number	124	12
White blood cell count increased
Additional description: White blood cell count increased
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Ear and labyrinth disorders
Auditory disorder
Additional description: Auditory disorder
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Deafness
Additional description: Deafness
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Ear discomfort
Additional description: Ear discomfort
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Ear pain
Additional description: Ear pain
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Hearing impaired
Additional description: Hearing impaired
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Tinnitus
Additional description: Tinnitus
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	2	0
Eye disorders
Dry eye
Additional description: Dry eye
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	2	0
Visual impairment
Additional description: Visual impairment
subjects affected / exposed	5 / 107 (4.67%)	2 / 111 (1.80%)
occurrences all number	5	2
Gastrointestinal disorders
Abdominal distension
Additional description: Abdominal distension
subjects affected / exposed	3 / 107 (2.80%)	0 / 111 (0.00%)
occurrences all number	6	0
Abdominal pain
Additional description: Abdominal pain
subjects affected / exposed	25 / 107 (23.36%)	16 / 111 (14.41%)
occurrences all number	40	16
Anal inflammation
Additional description: Anal inflammation
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	2	0
Aphthous ulcer
Additional description: Aphthous ulcer
subjects affected / exposed	3 / 107 (2.80%)	3 / 111 (2.70%)
occurrences all number	3	3
Ascites
Additional description: Ascites
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Breath odour
Additional description: Breath odour
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Cheilitis
Additional description: Cheilitis
subjects affected / exposed	3 / 107 (2.80%)	0 / 111 (0.00%)
occurrences all number	6	0
Dysphagia
Additional description: Dysphagia
subjects affected / exposed	7 / 107 (6.54%)	0 / 111 (0.00%)
occurrences all number	7	0
Diarrhoea
Additional description: Diarrhoea
subjects affected / exposed	52 / 107 (48.60%)	10 / 111 (9.01%)
occurrences all number	130	13
Dry mouth
Additional description: Dry mouth
subjects affected / exposed	10 / 107 (9.35%)	2 / 111 (1.80%)
occurrences all number	11	2
Dysgeusia
Additional description: Dysgeusia
subjects affected / exposed	6 / 107 (5.61%)	0 / 111 (0.00%)
occurrences all number	6	0
Dyspepsia
Additional description: Dyspepsia
subjects affected / exposed	4 / 107 (3.74%)	1 / 111 (0.90%)
occurrences all number	5	1
Constipation
Additional description: Constipation
subjects affected / exposed	29 / 107 (27.10%)	11 / 111 (9.91%)
occurrences all number	45	11
Gingival pain
Additional description: Gingival pain
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Faeces discoloured
Additional description: Faeces discoloured
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	3	0
Gastritis
Additional description: Gastritis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Gastrointestinal disorder
Additional description: Gastrointestinal disorder
subjects affected / exposed	5 / 107 (4.67%)	1 / 111 (0.90%)
occurrences all number	5	1
Gastrointestinal motility disorder
Additional description: Gastrointestinal motility disorder
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Gastrooesophageal reflux disease
Additional description: Gastrooesophageal reflux disease
subjects affected / exposed	0 / 107 (0.00%)	3 / 111 (2.70%)
occurrences all number	0	3
Gingivitis
Additional description: Gingivitis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Haematochezia
Additional description: Haematochezia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Haemorrhoids
Additional description: Haemorrhoids
subjects affected / exposed	7 / 107 (6.54%)	1 / 111 (0.90%)
occurrences all number	9	1
Intestinal transit time abnormal
Additional description: Intestinal transit time abnormal
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	2	0
Mouth ulceration
Additional description: Mouth ulceration
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Mucosal inflammation
Additional description: Mucosal inflammation
subjects affected / exposed	6 / 107 (5.61%)	1 / 111 (0.90%)
occurrences all number	11	2
Nausea
Additional description: Nausea
subjects affected / exposed	23 / 107 (21.50%)	14 / 111 (12.61%)
occurrences all number	28	15
Oesophagitis
Additional description: Oesophagitis
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Subileus
Additional description: Subileus
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Stomatitis
Additional description: Stomatitis
subjects affected / exposed	38 / 107 (35.51%)	3 / 111 (2.70%)
occurrences all number	51	3
Toothache
Additional description: Toothache
subjects affected / exposed	1 / 107 (0.93%)	1 / 111 (0.90%)
occurrences all number	1	1
Vomiting
Additional description: Vomiting
subjects affected / exposed	26 / 107 (24.30%)	12 / 111 (10.81%)
occurrences all number	33	12
Hepatobiliary disorders
Hyperbilirubinemia
Additional description: Hyperbilirubinemia
subjects affected / exposed	40 / 107 (37.38%)	10 / 111 (9.01%)
occurrences all number	97	18
Hypertransaminasemia
Additional description: Hypertransaminasemia
subjects affected / exposed	63 / 107 (58.88%)	35 / 111 (31.53%)
occurrences all number	246	82
Jaundice
Additional description: Jaundice
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Jaundice cholestatic
Additional description: Jaundice cholestatic
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Skin and subcutaneous tissue disorders
Acne
Additional description: Acne
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	2	0
Alopecia
Additional description: Alopecia
subjects affected / exposed	14 / 107 (13.08%)	1 / 111 (0.90%)
occurrences all number	15	1
Dry skin
Additional description: Dry skin
subjects affected / exposed	5 / 107 (4.67%)	2 / 111 (1.80%)
occurrences all number	6	2
Eczema
Additional description: Eczema
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Erythema
Additional description: Erythema
subjects affected / exposed	4 / 107 (3.74%)	0 / 111 (0.00%)
occurrences all number	4	0
Hair disorder
Additional description: Hair disorder
subjects affected / exposed	4 / 107 (3.74%)	0 / 111 (0.00%)
occurrences all number	4	0
Hand foot skin reaction
Additional description: Hand foot skin reaction
subjects affected / exposed	47 / 107 (43.93%)	3 / 111 (2.70%)
occurrences all number	86	3
Hyperkeratosis
Additional description: Hyperkeratosis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Pain of skin
Additional description: Pain of skin
subjects affected / exposed	2 / 107 (1.87%)	1 / 111 (0.90%)
occurrences all number	2	1
Nail disorder
Additional description: Nail disorder
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	2	0
Night sweats
Additional description: Night sweats
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Skin toxicity
Additional description: Skin toxicity
subjects affected / exposed	4 / 107 (3.74%)	1 / 111 (0.90%)
occurrences all number	7	1
Skin exfoliation
Additional description: Skin exfoliation
subjects affected / exposed	12 / 107 (11.21%)	0 / 111 (0.00%)
occurrences all number	13	0
Skin disorder
Additional description: Skin disorder
subjects affected / exposed	1 / 107 (0.93%)	2 / 111 (1.80%)
occurrences all number	1	2
Pruritus
Additional description: Pruritus
subjects affected / exposed	1 / 107 (0.93%)	3 / 111 (2.70%)
occurrences all number	1	3
Radiation skin injury
Additional description: Radiation skin injury
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	2	0
Rash
Additional description: Rash
subjects affected / exposed	22 / 107 (20.56%)	1 / 111 (0.90%)
occurrences all number	26	1
Urticaria
Additional description: Urticaria
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	2
Renal and urinary disorders
Chromaturia
Additional description: Chromaturia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Dysuria
Additional description: Dysuria
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Nocturia
Additional description: Nocturia
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Pollakiuria
Additional description: Pollakiuria
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Proteinuria
Additional description: Proteinuria
subjects affected / exposed	11 / 107 (10.28%)	9 / 111 (8.11%)
occurrences all number	14	9
Pyelocaliectasis
Additional description: Pyelocaliectasis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Urinary retention
Additional description: Urinary retention
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Endocrine disorders
Blood thyroid stimulating hormone decreased
Additional description: Blood thyroid stimulating hormone decreased
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	2	0
Blood thyroid stimulating hormone increased
Additional description: Blood thyroid stimulating hormone increased
subjects affected / exposed	3 / 107 (2.80%)	0 / 111 (0.00%)
occurrences all number	3	0
Cushingoid
Additional description: Cushingoid
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Hyperparathyroidism
Additional description: Hyperparathyroidism
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Hyperthyroidism
Additional description: Hyperthyroidism
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	3	0
Hypothyroidism
Additional description: Hypothyroidism
subjects affected / exposed	7 / 107 (6.54%)	1 / 111 (0.90%)
occurrences all number	9	1
Thyroid disorder
Additional description: Thyroid disorder
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Tri-iodothyronine decreased
Additional description: Tri-iodothyronine decreased
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
Additional description: Arthralgia
subjects affected / exposed	15 / 107 (14.02%)	8 / 111 (7.21%)
occurrences all number	21	10
Back pain
Additional description: Back pain
subjects affected / exposed	11 / 107 (10.28%)	10 / 111 (9.01%)
occurrences all number	12	11
Bone pain
Additional description: Bone pain
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Chondrocalcinosis
Additional description: Chondrocalcinosis
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Fistula
Additional description: Fistula
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Flank pain
Additional description: Flank pain
subjects affected / exposed	2 / 107 (1.87%)	1 / 111 (0.90%)
occurrences all number	2	1
Muscle spasms
Additional description: Muscle spasms
subjects affected / exposed	7 / 107 (6.54%)	4 / 111 (3.60%)
occurrences all number	8	4
Joint effusion
Additional description: Joint effusion
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Osteoarthritis
Additional description: Osteoarthritis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Pain in extremity
Additional description: Pain in extremity
subjects affected / exposed	17 / 107 (15.89%)	4 / 111 (3.60%)
occurrences all number	20	4
Pain in jaw
Additional description: Pain in jaw
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Musculoskeletal chest pain
Additional description: Musculoskeletal chest pain
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Musculoskeletal disorder
Additional description: Musculoskeletal disorder
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Musculoskeletal pain
Additional description: Musculoskeletal pain
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	3	0
Myalgia
Additional description: Myalgia
subjects affected / exposed	15 / 107 (14.02%)	4 / 111 (3.60%)
occurrences all number	17	4
Neck pain
Additional description: Neck pain
subjects affected / exposed	3 / 107 (2.80%)	1 / 111 (0.90%)
occurrences all number	3	1
Tendon disorder
Additional description: Tendon disorder
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Scoliosis
Additional description: Scoliosis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Torticollis
Additional description: Torticollis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Infections and infestations
Bronchitis
Additional description: Bronchitis
subjects affected / exposed	4 / 107 (3.74%)	1 / 111 (0.90%)
occurrences all number	4	1
Device related infection
Additional description: Device related infection
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Ear infection
Additional description: Ear infection
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Erysipelas
Additional description: Erysipelas
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Fungal sepsis
Additional description: Fungal sepsis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Gastroenteritis
Additional description: Gastroenteritis
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Infection
Additional description: Infection
subjects affected / exposed	2 / 107 (1.87%)	1 / 111 (0.90%)
occurrences all number	3	1
Pharyngitis
Additional description: Pharyngitis
subjects affected / exposed	2 / 107 (1.87%)	1 / 111 (0.90%)
occurrences all number	2	1
Nasopharyngitis
Additional description: Nasopharyngitis
subjects affected / exposed	1 / 107 (0.93%)	3 / 111 (2.70%)
occurrences all number	1	3
Sinusitis
Additional description: Sinusitis
subjects affected / exposed	2 / 107 (1.87%)	0 / 111 (0.00%)
occurrences all number	2	0
Sepsis
Additional description: Sepsis
subjects affected / exposed	1 / 107 (0.93%)	1 / 111 (0.90%)
occurrences all number	1	1
Rhinitis
Additional description: Rhinitis
subjects affected / exposed	0 / 107 (0.00%)	4 / 111 (3.60%)
occurrences all number	0	4
Vaginal infection
Additional description: Vaginal infection
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Urinary tract infection
Additional description: Urinary tract infection
subjects affected / exposed	3 / 107 (2.80%)	1 / 111 (0.90%)
occurrences all number	5	1
Tracheitis
Additional description: Tracheitis
subjects affected / exposed	0 / 107 (0.00%)	2 / 111 (1.80%)
occurrences all number	0	2
Tooth infection
Additional description: Tooth infection
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Tonsillitis
Additional description: Tonsillitis
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Vulvovaginal mycotic infection
Additional description: Vulvovaginal mycotic infection
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0
Viral upper respiratory tract infection
Additional description: Viral upper respiratory tract infection
subjects affected / exposed	0 / 107 (0.00%)	1 / 111 (0.90%)
occurrences all number	0	1
Viral infection
Additional description: Viral infection
subjects affected / exposed	1 / 107 (0.93%)	0 / 111 (0.00%)
occurrences all number	1	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

09 Aug 2013

Removal of exclusion criterion No. 25, clarification/modification of eligibility criteria, change of service provider for drug management, addition of procedures for reporting serious adverse events related to pregnancy, addition of investigation centers. Addition of German coordinator, update of study schedule, correction of typographical errors, modification of contact details

22 Nov 2013

New participating centers / Change of IP Appendix C of the protocol: clarification of histology

18 Jun 2014

MS1 (Austria ) Participation of Germany, Change in eligibility criteria Details on the declaration of SAEs for pregnancies

16 Sep 2015

Change in the person responsible for secondary packaging, labeling, and distribution of the product

08 Oct 2015

Addition of cohort E (change in the number of patients to be included, change in selection criteria, extension of the study duration), modification of liver monitoring procedures and treatment adjustments to be adopted in the event of liver toxicity, update of the study schedule, modifications to paragraph 8.8 “Dose reductions and treatment delay” following the update of the SPCs, update of the section on interactions with other medicinal products Update of the contact details of the persons involved in the study at the sponsor's site

23 May 2016

Update of the list of participating centers

04 Oct 2016

- Modification of a non-inclusion criterion: “More than 3 to 4 lines of systemic treatment for metastatic sarcoma.” - Addition of a stratification criterion in cohort E: “Number of lines of systemic treatment for metastatic sarcoma: 0 to 3 lines versus 4 lines.” - 24-month extension and update of protocol signatories

16 Dec 2016

MS2 (Austria) Addition of cohort E (change in the number of patients to be included, change in selection criteria, extension of the study duration), modification of liver monitoring procedures and treatment djustments to be adopted in the event of liver toxicity, update of the study schedule, modifications to paragraph 8.8 “Dose reductions and treatment delay” following the update of the SPCs, update of the section on interactions with other medicinal products. Change in protocol signatories, change in the sponsor team, update to the study schedule

28 Apr 2017

- Temporary halt to recruitment (problem with supply of treatment in the study) - Update of the list of participating centers

19 Sep 2017

- Recruitment resumes as of 09/19/17 - Update of the list of participating centers

20 Oct 2017

- BI update (version 12) + update with BI v 9-10-11 + BI update (version 13) following the ANSM NR Following the BI update (versions 12 and 13): changes to expected adverse events and actions to be taken in the event of infection - Update of the list of participating centers - modification of NICE

12 Mar 2019

RGPD compliance

04 Nov 2019

- BI update (versions 14 and 15) - Update of the list of participating centers

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
28 Apr 2017	Temporary halt to recruitment (problem with supply of treatment in the study)	19 Sep 2017

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/27751846
http://www.ncbi.nlm.nih.gov/pubmed/29902612
http://www.ncbi.nlm.nih.gov/pubmed/31918233
http://www.ncbi.nlm.nih.gov/pubmed/28295221
http://www.ncbi.nlm.nih.gov/pubmed/29722789
http://www.ncbi.nlm.nih.gov/pubmed/33322802

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Clinical trials

Clinical Trial Results: Activity and safety of regorafenib in patients with metastatic. Soft tissue sarcoma previously treated with anthracyclin-based chemotherapy: a multinational, randomized, phase II, placebo-controlled trial

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Progression-free survival - cohort A

Primary: Progression-free survival - cohort A

Primary: Progression-free survival - cohort B

Primary: Progression-free survival - cohort B

Primary: Progression-free survival - cohort C

Primary: Progression-free survival - cohort C

Primary: Progression-free survival - cohort D

Primary: Progression-free survival - cohort D

Primary: Progression-free survival - cohort E

Primary: Progression-free survival - cohort E

Secondary: Overall Survival - cohort A

Secondary: Overall Survival - cohort A

Secondary: Overall Survival - cohort B

Secondary: Overall Survival - cohort B

Secondary: Best tumor response, according to full central review -Cohort B

Secondary: Best tumor response, according to full central review -Cohort B

Secondary: Overall Survival - cohort C

Secondary: Overall Survival - cohort C

Secondary: Best tumor response, according to full central review -Cohort C

Secondary: Best tumor response, according to full central review -Cohort C

Secondary: Overall Survival - cohort D

Secondary: Overall Survival - cohort D

Secondary: Best tumor response, according to full central review -Cohort D

Secondary: Best tumor response, according to full central review -Cohort D

Secondary: Overall Survival - cohort E

Secondary: Overall Survival - cohort E

Secondary: Best tumor response, according to full central review -Cohort E

Secondary: Best tumor response, according to full central review -Cohort E

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
Activity and safety of regorafenib in patients with metastatic. Soft tissue sarcoma previously treated with anthracyclin-based chemotherapy: a multinational, randomized, phase II, placebo-controlled trial