Download PDF

Clinical Trial Results:
A Multicentre, Open-Label, Early Stopping Design, Proof of Concept Study with Tasquinimod in Treating Patients with Advanced or Metastatic Hepatocellular, Ovarian, Renal Cell and Gastric Carcinomas

Summary
EudraCT number	2012-002326-75
Trial protocol	GB BE ES
Global end of trial date	11 Apr 2016

Results information
Results version number	v1(current)
This version publication date	09 Sep 2017
First version publication date	09 Sep 2017
Other versions

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

8-55-58102-004

ISRCTN number

US NCT number

NCT01743469

WHO universal trial number (UTN)

Sponsor organisation name

Ipsen Pharma

Sponsor organisation address

65 quai Georges Gorse, Boulogne-Billancourt, France, 92100

Public contact

Medical Director, Oncology, Ipsen Pharma, clinical.trials@ipsen.com

Scientific contact

Medical Director, Oncology, Ipsen Pharma, clinical.trials@ipsen.com

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

03 Dec 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

03 Dec 2014

Global end of trial reached?

Yes

Global end of trial date

11 Apr 2016

Was the trial ended prematurely?

Main objective of the trial

To determine the clinical activity of tasquinimod in advanced or metastatic hepatocellular, ovarian, renal cell and gastric carcinomas in patients who progressed after standard therapies. Clinical activity was measured by the proportion of patients who had neither progressed nor died at a prespecified timepoint (progression free survival [PFS] rate): • In advanced or metastatic hepatocellular carcinoma after one line of sorafenib • In advanced or metastatic ovarian carcinoma resistant to platinum-containing therapy • In metastatic renal cell carcinoma previously treated with vascular endothelial growth factor (VEGF) inhibitor • In advanced or metastatic gastric carcinoma after one line of platinum-containing therapy.

Protection of trial subjects

The study was conducted under the provisions of the Declaration of Helsinki, and in accordance with the International Conference on Harmonisation Consolidated Guideline on Good Clinical Practice.

Background therapy

Evidence for comparator

Actual start date of recruitment

10 Dec 2012

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

9 Months

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 38

Country: Number of subjects enrolled

Spain: 7

Country: Number of subjects enrolled

United Kingdom: 41

Country: Number of subjects enrolled

Belgium: 15

Country: Number of subjects enrolled

France: 66

Worldwide total number of subjects

167

EEA total number of subjects

129

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)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Patients were recruited from 24 investigational sites in Belgium, Canada, the United Kingdom, Spain and France. The first patient was enrolled on 10 December 2012 and the end of study was 11 April 2016. The cut-off date for final analysis was the 3 December 2014.

Screening details

In the hepatocellular carcinoma cohort 67 patients were screened, of whom 53 were treated with tasquinimod. In the ovarian carcinoma cohort 63 were screened, of whom 55 were treated. In the renal cell carcinoma cohort 44 were screened, of whom 38 were treated. In the gastric carcinoma cohort 27 were screened, of whom 21 were treated.

Period 1 title

Active Treatment Phase (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Hepatocellular Carcinoma Cohort

Arm description

Patients with advanced or metastatic hepatocellular carcinoma after one line of sorafenib therapy were administered a starting dose of tasquinimod 0.5 milligrams (mg)/day for at least 2 weeks. After at least 2 weeks the dose was adjusted depending on individual safety and tolerability to be either increased to 1 mg/day, reduced to 0.25 mg/day or maintained at 0.5 mg/day. Patients continued to receive daily oral doses of tasquinimod 0.25, 0.5 or 1 mg/day until disease progression, lost to follow-up, withdrawal or death. An end of study/withdrawal visit was performed at least 14 days after the last dose of study medication and/or before the intitiation of any new cancer treatment. The patient was then followed up for survival every 3 months after the last study treatment dose until death, lost to follow-up, withdrawal of consent or until end of study on 11 April 2016.

Arm type

Experimental

Investigational medicinal product name

Tasquinimod

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Patients were administered single daily oral doses of tasquinimod provided as hard gelatine capsules in strengths of 0.25 mg, 0.5 mg or 1 mg.

Ovarian Carcinoma Cohort

Arm description

Patients with advanced or metastatic ovarian carcinoma resistant to platinum-containing therapy were administered a starting dose of tasquinimod 0.5 mg/day for at least 2 weeks. After at least 2 weeks the dose was adjusted depending on individual safety and tolerability to be either increased to 1 mg/day, reduced to 0.25 mg/day or maintained at 0.5 mg/day. Patients continued to receive daily oral doses of tasquinimod 0.25, 0.5 or 1 mg/day until disease progression, lost to follow-up, withdrawal or death. An end of study/withdrawal visit was performed at least 14 days after the last dose of study medication and/or before the intitiation of any new cancer treatment.The patient was then followed up for survival every 3 months after the last study treatment dose until death, lost to follow-up, withdrawal of consent or until end of study on 11 April 2016.

Arm type

Experimental

Investigational medicinal product name

Tasquinimod

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Patients were administered single daily oral doses of tasquinimod provided as hard gelatine capsules in strengths of 0.25 mg, 0.5 mg or 1 mg.

Renal Cell Carcinoma

Arm description

Patients with metastatic renal cell carcinoma previously treated with VEGF inhibitor were administered a starting dose of tasquinimod 0.5 mg/day for at least 2 weeks. After at least 2 weeks the dose was adjusted depending on individual safety and tolerability to be either increased to 1 mg/day, reduced to 0.25 mg/day or maintained at 0.5 mg/day. Patients continued to receive daily oral doses of tasquinimod 0.25, 0.5 or 1 mg/day until disease progression, lost to follow-up, withdrawal or death. An end of study/withdrawal visit was performed at least 14 days after the last dose of study medication and/or before the intitiation of any new cancer treatment. The patient was then followed up for survival every 3 months after the last study treatment dose until death, lost to follow-up, withdrawal of consent or until end of study on 11 April 2016.

Arm type

Experimental

Investigational medicinal product name

Tasquinimod

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Patients were administered single daily oral doses of tasquinimod provided as hard gelatine capsules in strengths of 0.25 mg, 0.5 mg or 1 mg.

Gastric Carcinoma Cohort

Arm description

Patients with advanced or metastatic gastric carcinoma after one line of platinum-containing therapy were administered a starting dose of tasquinimod 0.5 mg/day for at least 2 weeks. After at least 2 weeks the dose was adjusted depending on individual safety and tolerability to be either increased to 1 mg/day, reduced to 0.25 mg/day or maintained at 0.5 mg/day. Patients continued to receive daily oral doses of tasquinimod 0.25, 0.5 or 1 mg/day until disease progression, lost to follow-up, withdrawal or death. An end of study/withdrawal visit was performed at least 14 days after the last dose of study medication and/or before the intitiation of any new cancer treatment. The patient was then followed up for survival every 3 months after the last study treatment dose until death, lost to follow-up, withdrawal of consent or until end of study on 11 April 2016.

Arm type

Experimental

Investigational medicinal product name

Tasquinimod

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule, hard

Routes of administration

Oral use

Dosage and administration details

Patients were administered single daily oral doses of tasquinimod provided as hard gelatine capsules in strengths of 0.25 mg, 0.5 mg or 1 mg.

Number of subjects in period 1	Hepatocellular Carcinoma Cohort	Ovarian Carcinoma Cohort	Renal Cell Carcinoma	Gastric Carcinoma Cohort
Started	53	55	38	21
Treatment ongoing at analysis cut-off	3 ^[1]	3 ^[2]	0 ^[3]	0 ^[4]
Entering into Post-treatment Follow-up	49	48	37	21
Completing Post-treatment Follow-up	9	25	14	5
Completed	9	25	14	5
Not completed	44	30	24	16
Did not enter follow-up period	4	7	1	-
Consent withdrawn by subject	1	-	1	-
Death	38	22	22	16
Lost to follow-up	1	1	-	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who did not complete the active treatment phase were able to enter in the post-treatment follow-up phase.
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who did not complete the active treatment phase were able to enter in the post-treatment follow-up phase.
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who did not complete the active treatment phase were able to enter in the post-treatment follow-up phase.
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: Subjects who did not complete the active treatment phase were able to enter in the post-treatment follow-up phase.

Baseline characteristics

Top of page

Reporting group title

Hepatocellular Carcinoma Cohort

Reporting group description

Reporting group title

Ovarian Carcinoma Cohort

Reporting group description

Reporting group title

Renal Cell Carcinoma

Reporting group description

Reporting group title

Gastric Carcinoma Cohort

Reporting group description

Reporting group values	Hepatocellular Carcinoma Cohort	Ovarian Carcinoma Cohort	Renal Cell Carcinoma	Gastric Carcinoma Cohort	Total
Number of subjects	53	55	38	21	167
Age categorical
Units: Subjects
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0
Adults (18-64 years)	19	34	25	11	89
From 65-84 years	34	21	13	10	78
85 years and over	0	0	0	0	0
Gender categorical
Units: Subjects
Female	8	55	10	4	77
Male	45	0	28	17	90
Ethnicity
Units: Subjects
Hispanic or Latino	1	0	1	0	2
Not Hispanic or Latino	33	53	33	19	138
Unknown or Not Reported	19	2	4	2	27
Race
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0
Asian	3	2	0	2	7
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	2	2	0	0	4
White	29	49	35	17	130
More than one race	0	0	0	0	0
Unknown or Not Reported	19	2	3	2	26

End points

Top of page

Reporting group title

Hepatocellular Carcinoma Cohort

Reporting group description

Reporting group title

Ovarian Carcinoma Cohort

Reporting group description

Reporting group title

Renal Cell Carcinoma

Reporting group description

Reporting group title

Gastric Carcinoma Cohort

Reporting group description

Primary: PFS Rate based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) Criteria (All Cohorts)

Top of page

End point title

PFS Rate based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) Criteria (All Cohorts) ^[1]

End point description

The PFS rate was defined as the percentage of patients who neither progressed nor died at the time of the final analysis (predefined timepoint T2) and is reported for each cohort. Final analysis was performed for each cohort after a predefined number of patients had reached time T2. The PFS rate was calculated according to the RECIST v1.1 criteria. A patient was considered as neither progressed nor died if central assessment using RECIST v1.1 confirmed no disease progression was observed between the start of study medication and the last examination/visit date of complete response (CR) or partial response (PR) or stable disease (SD) greater than or equal to the analysis timepoint -7 days. Data is presented for the Intent to treat (ITT) Population which consisted of all treated patients who received at least one dose of tasquinimod.

End point type

Primary

End point timeframe

Predefined timepoint T2 for each cohort: Week 12 (gastric carcinoma cohort); Week 16 (hepatocellular carcinoma cohort and renal cell carcinoma cohort) and Week 24 (ovarian carcinoma cohort)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Each cohort was analysed separately by comparing the PFS rate with a prespecified threshold using a one-sided alpha of 0.1. For the Hepatocellular Carcinoma Cohort the threshold was >20% (p=0.142). For the Ovarian Carcinoma Cohort the threshold was >35% (p=1.000). For the Renal Cell Carcinoma Cohort the threshold was >20% (p=0.800). For the Gastric Carcinoma Cohort the threshold was >15% (p=0.630).

End point values	Hepatocellular Carcinoma Cohort	Ovarian Carcinoma Cohort	Renal Cell Carcinoma	Gastric Carcinoma Cohort
Number of subjects analysed	52	55	38	21
Units: Percentage of Participants
number (confidence interval 95%)	26.9 (15.57 to 41.02)	7.3 (2.02 to 17.59)	13.2 (4.41 to 28.09)	9.5 (1.17 to 30.38)

No statistical analyses for this end point

Secondary: PFS Rate measured by the Choi criteria (Hepatocellular Carcinoma Cohort)

Top of page

End point title

PFS Rate measured by the Choi criteria (Hepatocellular Carcinoma Cohort) ^[2]

End point description

The PFS rate, defined as the percentage of patients who neither progressed nor died at the time of analysis, was determined for the hepatocellular carcinoma cohort at Week 16 using the Choi criteria. The Choi criteria is used to assess tumour progression in patients with advanced heptaocellular carcinoma. Tumour progression was determined as follows: CR: Disappearance of all lesions and no new lesions. PR: Decrease in tumour size ≥10% or decrease in tumour density ≥15% on Computerised Tomography Scan. SD: Does not meet criteria for CR, PR or progressive disease (PD). PD: Increase in tumour size ≥10% and does not meet PR criteria by tumour density. Data is presented for the ITT population in the hepatocellular carcinoma cohort which consisted of all treated patients who received at least one dose of tasquinimod.

End point type

Secondary

End point timeframe

Predefined timepoint T2 for hepatocellular carcinoma cohort: Week 16.

Notes
[2] - 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: This endpoint presents data as determined using the Choi criteria which is used to assess tumour progression in advanced hepatocellular carcinoma and is therefore only relevant to the hepatocellular carcinoma cohort.

End point values	Hepatocellular Carcinoma Cohort
Number of subjects analysed	53
Units: Percentage of Participants
number (confidence interval 95%)	20.8 (10.84 to 34.11)

No statistical analyses for this end point

Secondary: Best Overall Response and Response Rates using RECIST v1.1 for (All Cohorts)

Top of page

End point title

Best Overall Response and Response Rates using RECIST v1.1 for (All Cohorts)

End point description

The best overall response assessed centrally and locally using RECIST v1.1 criteria was determined for all cohorts, and the patients were assigned to one of the following categories: PR: At least a 30% decrease in the sum of the greatest unidimensional diameters of target lesions. SD: Any cases that do not qualify for either PR or PD. PD: An increase of at least 20% in the sum of the diameters of target lesions. Not evaluable (NE): Tumour assessment was absent or patient was withdrawn due to TEAEs. Response rates for each cohort are also presented as the percentage of patients who were responders in each cohort. A patient was considered a responder if the best overall response was either CR or PR. CR was defined as the disappearance of all target lesions. Data is presented for the ITT population which consisted of all treated patients who received at least one dose of tasquinimod.

End point type

Secondary

End point timeframe

At 8 week intervals up to 36 months for hepatocellular carcinoma, ovarian carcinoma and renal cell carcinoma cohorts. At 6 week intervals until Week 24 and then every 8 weeks up to 36 months for the gastric carcinoma cohort.

End point values	Hepatocellular Carcinoma Cohort	Ovarian Carcinoma Cohort	Renal Cell Carcinoma	Gastric Carcinoma Cohort
Number of subjects analysed	53	55	38	21
Units: percentage of participants
number (confidence interval 95%)
Best overall response = PR (central RECIST)	1.9 (0.05 to 10.07)	1.8 (0.05 to 9.72)	0 (0 to 0)	0 (0 to 0)
Best overall response = SD (central RECIST)	54.7 (40.45 to 68.44)	49.1 (35.35 to 62.93)	47.4 (30.98 to 64.18)	23.8 (8.22 to 47.17)
Best overall response = PD (central RECIST)	34 (21.52 to 48.27)	41.8 (28.65 to 55.89)	44.7 (28.62 to 61.7)	66.7 (43.03 to 85.41)
Best overall response = NE (central RECIST)	9.4 (3.13 to 20.66)	7.3 (2.02 to 17.59)	7.9 (1.66 to 21.38)	9.5 (1.17 to 30.38)
Response Rate (central RECIST)	1.9 (0.05 to 10.07)	1.8 (0.05 to 9.72)	0 (0 to 0)	0 (0 to 0)
Best overall response = PR (local RECIST)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)
Best overall response = SD (local RECIST)	52.8 (38.64 to 66.7)	32.7 (20.68 to 46.71)	39.5 (24.04 to 56.61)	14.3 (3.05 to 36.34)
Best overall response = PD (local RECIST)	43.4 (29.84 to 57.72)	61.8 (47.73 to 74.59)	57.9 (40.82 to 73.69)	81 (58.09 to 94.55)
Best overall response = NE (local RECIST)	3.8 (0.46 to 12.98)	5.5 (1.14 to 15.12)	2.6 (0.07 to 13.81)	4.8 (0.12 to 23.82)
Response Rate (local RECIST)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)

No statistical analyses for this end point

Secondary: Best Overall Response and Response Rates using Choi criteria (Hepatocellular Carcinoma Cohort)

Top of page

End point title

Best Overall Response and Response Rates using Choi criteria (Hepatocellular Carcinoma Cohort) ^[3]

End point description

The best overall response assessed centrally using the Choi criteria was determined for the hepatocellular carcinoma cohort, and the patients were assigned to one of the following categories: PR: Decrease in tumour size ≥10% or decrease in tumour density ≥15% on Computerised Tomography Scan. SD: Does not meet criteria for CR, PR or PD. PD: Increase in tumour size ≥10% and does not meet PR criteria by tumour density. NE: Tumour assessment was absent or patient was withdrawn due to TEAEs. The Response Rate for each cohort is also presented as the percentage of patients who were responders. A patient was considered a responder if the best overall response was either CR or PR. CR was defined as the disappearance of all target lesions. Data is presented for the ITT population in the hepatocellular carcinoma cohort which consisted of all treated patients who received at least one dose of tasquinimod.

End point type

Secondary

End point timeframe

At 8 week intervals up to 36 months.

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: This endpoint presents data as determined using the Choi criteria which is used to assess tumour progression in advanced hepatocellular carcinoma and is therefore only relevant to the hepatocellular carcinoma cohort.

End point values	Hepatocellular Carcinoma Cohort
Number of subjects analysed	53
Units: Percentage of Participants
number (confidence interval 95%)
Best overall response = PR (central Choi)	20.8 (10.84 to 34.11)
Best overall response = SD (central Choi)	32.1 (19.92 to 46.32)
Best overall response = PD (central Choi)	34 (21.52 to 48.27)
Best overall response = NE (central Choi)	13.2 (5.48 to 25.34)
Response Rate (central Choi)	20.8 (10.84 to 34.11)

No statistical analyses for this end point

Secondary: Clinical Benefit according to RECIST v1.1 (All Cohorts)

Top of page

End point title

Clinical Benefit according to RECIST v1.1 (All Cohorts)

End point description

Clinical benefit was defined for a patient if CR, PR or SD was observed at least 12 weeks after the first study medication using local and central RECIST v1.1 assessments. The percentage of patients with clinical benefit is presented for each cohort. Data is presented for the ITT population which consisted of all treated patients who received at least one dose of tasquinimod.

End point type

Secondary

End point timeframe

End point values	Hepatocellular Carcinoma Cohort	Ovarian Carcinoma Cohort	Renal Cell Carcinoma	Gastric Carcinoma Cohort
Number of subjects analysed	53	55	38	21
Units: Percentage of Participants
number (confidence interval 95%)
Clinical benefit (central RECIST)	26.4 (15.26 to 40.33)	20 (10.43 to 32.97)	15.8 (6.02 to 31.25)	0 (0 to 0)
Clinical benefit (local RECIST)	32.1 (19.92 to 46.32)	16.4 (7.77 to 28.8)	15.8 (6.02 to 31.25)	0 (0 to 0)

No statistical analyses for this end point

Secondary: Median PFS from First Study Treatment to Progression or death due to any cause (Hepatocellular Carcinoma Cohort)

Top of page

End point title

Median PFS from First Study Treatment to Progression or death due to any cause (Hepatocellular Carcinoma Cohort) ^[4]

End point description

The median PFS from first study treatment to first progression as defined using the Choi criteria or death from any cause is presented for the hepatocellular carcinoma cohort. PD is defined in the Choi criteria as an increase in tumour size ≥10% and does not meet PR criteria by tumour density. Data is presented for the ITT population which consisted of all treated patients who received at least one dose of tasquinimod.

End point type

Secondary

End point timeframe

At 8 week intervals up to 36 months.

Notes
[4] - 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: This endpoint presents data as determined using the Choi criteria which is used to assess tumour progression in advanced hepatocellular carcinoma and is therefore only relevant to the hepatocellular carcinoma cohort.

End point values	Hepatocellular Carcinoma Cohort
Number of subjects analysed	53
Units: Weeks
median (confidence interval 95%)	15.71 (8 to 16.43)

No statistical analyses for this end point

Secondary: Median PFS from first study treatment to progression or death due to any cause using RECIST v1.1 criteria (All Cohorts)

Top of page

End point title

Median PFS from first study treatment to progression or death due to any cause using RECIST v1.1 criteria (All Cohorts)

End point description

The median PFS from first study treatment to first progression as defined using the RECIST v1.1 criteria or death from any cause is presented for all cohorts. The median PFS for central and local assessments are presented. PD is defined in the RECIST v1.1 criteria as an increase of at least 20% in the sum of the diameters of target lesions. Data is presented for the ITT population which consisted of all treated patients who received at least one dose of tasquinimod.

End point type

Secondary

End point timeframe

End point values	Hepatocellular Carcinoma Cohort	Ovarian Carcinoma Cohort	Renal Cell Carcinoma	Gastric Carcinoma Cohort
Number of subjects analysed	53	55	38	21
Units: Weeks
median (confidence interval 95%)
PFS (central RECIST)	15.86 (8 to 23.14)	8 (7.71 to 17.43)	14.86 (7.86 to 16.71)	6 (5.29 to 7.29)
PFS (local RECIST)	15.71 (8 to 16.43)	7.57 (7 to 7.86)	7.86 (7.29 to 14.71)	5.79 (5.14 to 6.86)

No statistical analyses for this end point

Secondary: Time to Progression (TTP) using the Choi criteria (Hepatocellular Carcinoma Cohort)

Top of page

End point title

Time to Progression (TTP) using the Choi criteria (Hepatocellular Carcinoma Cohort) ^[5]

End point description

The median TTP as determined using the Choi criteria from the first study medication date up to the first occurrence of a progression or death due to disease progression before initiation of new systemic treatment is presented for the hepatocellular carcinoma cohort. PD is defined in the Choi criteria as an increase in tumour size ≥10% and does not meet PR criteria by tumour density. Data is presented for the ITT population which consisted of all treated patients who received at least one dose of tasquinimod.

End point type

Secondary

End point timeframe

At 8 week intervals up to 36 months.

Notes
[5] - 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: This endpoint presents data as determined using the Choi criteria which is used to assess tumour progression in advanced hepatocellular carcinoma and is therefore only relevant to the hepatocellular carcinoma cohort.

End point values	Hepatocellular Carcinoma Cohort
Number of subjects analysed	53
Units: Weeks
median (confidence interval 95%)	15.86 (8.43 to 16.43)

No statistical analyses for this end point

Secondary: TTP using RECIST v1.1 criteria (All Cohorts)

Top of page

End point title

TTP using RECIST v1.1 criteria (All Cohorts)

End point description

The median TTP as determined using RECIST v1.1 criteria from the first study medication date up to the first occurrence of a progression or death due to disease progression before initiation of new systemic treatment is presented for all cohorts. The median TTP for central and local assessments are presented. PD is defined in RECIST v1.1 as an increase of at least 20% in the sum of the diameters of target lesions. Data is presented for the ITT population which consisted of all treated patients who received at least one dose of tasquinimod.

End point type

Secondary

End point timeframe

End point values	Hepatocellular Carcinoma Cohort	Ovarian Carcinoma Cohort	Renal Cell Carcinoma	Gastric Carcinoma Cohort
Number of subjects analysed	53	55	38	21
Units: Weeks
median (confidence interval 95%)
TTP (central RECIST)	15.86 (8.43 to 24)	8 (7.71 to 17.43)	14.86 (7.86 to 16)	6 (5.29 to 7.29)
TTP (local RECIST)	15.71 (8 to 16.43)	7.57 (7 to 7.86)	7.86 (7.29 to 14.71)	5.79 (5.14 to 6.86)

No statistical analyses for this end point

Secondary: Overall Survival (OS) from first study treatment to death due to any cause (All Cohorts)

Top of page

End point title

Overall Survival (OS) from first study treatment to death due to any cause (All Cohorts)

End point description

OS was defined as the time (in weeks) from first study medication date to death due to any cause. Patients were censored at the date of last contact (the latest between the time of end of study or withdrawal assessment and follow-up visits). The median OS is presented for all cohorts. Data is presented for the ITT population which consisted of all treated patients who received at least one dose of tasquinimod.

End point type

Secondary

End point timeframe

Time from first study treatment up to 36 months.

End point values	Hepatocellular Carcinoma Cohort	Ovarian Carcinoma Cohort	Renal Cell Carcinoma	Gastric Carcinoma Cohort
Number of subjects analysed	53	55 ^[6]	38	21
Units: Weeks
median (confidence interval 95%)	29.29 (25 to 38.71)	0 (0 to 0)	32.71 (26.43 to 40.86)	21.57 (13.86 to 33.29)

Notes
[6] - The median was not reached. Results: NC (30.71, NC).

No statistical analyses for this end point

Secondary: Further cancer-related treatment during the follow-up period for (All Cohorts)

Top of page

End point title

Further cancer-related treatment during the follow-up period for (All Cohorts)

End point description

Further systemic treatment was coded using the World Health Organisation Dictionary (June 2014 version for hepatocellular carcinoma cohort and June 2013 version for all other cohorts). The number of patients who received further systemic treatment during the follow-up period is presented for all cohorts.

End point type

Secondary

End point timeframe

From the end of study/withdrawal visit at the end of the active treatment period to the end of the follow-up period.

End point values	Hepatocellular Carcinoma Cohort	Ovarian Carcinoma Cohort	Renal Cell Carcinoma	Gastric Carcinoma Cohort
Number of subjects analysed	53	55	38	21
Units: Participants	16	35	18	8

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

TEAEs were collected during the active phase of the study from treatment start date until predefined timepoint T2.

Adverse event reporting additional description

Tumour-related signs and symptoms were recorded as TEAEs during the study only if they worsened in severity or increased in frequency. The Safety population comprised all patients who had received at least one dose of tasquinimod. AEs were coded using MedDRA 17.1 for the Hepatocellular Carcinoma cohort and version 16.1 for all other cohorts.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

Hepatocellular Carcinoma Cohort

Reporting group description

Patients with advanced or metastatic hepatocellular carcinoma after one line of sorafenib therapy were administered a starting dose of tasquinimod 0.5 mg/day for at least 2 weeks. After at least 2 weeks the dose was adjusted depending on individual safety and tolerability to be either increased to 1 mg/day, reduced to 0.25 mg/day or maintained at 0.5 mg/day. Patients continued to receive daily oral doses of tasquinimod 0.25, 0.5 or 1.0 mg/day until disease progression, lost to follow-up, withdrawal or death. An end of study/withdrawal visit was performed at least 14 days after the last dose of study treatment and/or before the intitiation of any new cancer treatment. The patient was then followed up for survival every 3 months after the last study treatment dose until death, lost to follow-up, withdrawal of consent or until all patients completed at least 9 months of follow-up.

Reporting group title

Ovarian Carcinoma Cohort

Reporting group description

Patients with advanced or metastatic ovarian carcinoma resistant to platinum-containing therapy were administered a starting dose of tasquinimod 0.5 mg/day for at least 2 weeks. After at least 2 weeks the dose was adjusted depending on individual safety and tolerability to be either increased to 1 mg/day, reduced to 0.25 mg/day or maintained at 0.5 mg/day. Patients continued to receive daily oral doses of tasquinimod 0.25, 0.5 or 1.0 mg/day until disease progression, lost to follow-up, withdrawal or death. An end of study/withdrawal visit was performed at least 14 days after the last dose of study treatment and/or before the intitiation of any new cancer treatment. The patient was then followed up for survival every 3 months after the last study treatment dose until death, lost to follow-up, withdrawal of consent or until all patients completed at least 9 months of follow-up.

Reporting group title

Renal Cell Carcinoma

Reporting group description

Patients with metastatic renal cell carcinoma previously treated with VEGF inhibitor were administered a starting dose of tasquinimod 0.5 mg/day for at least 2 weeks. After at least 2 weeks the dose was adjusted depending on individual safety and tolerability to be either increased to 1 mg/day, reduced to 0.25 mg/day or maintained at 0.5 mg/day. Patients continued to receive daily oral doses of tasquinimod 0.25, 0.5 or 1.0 mg/day until disease progression, lost to follow-up, withdrawal or death. An end of study/withdrawal visit was performed at least 14 days after the last dose of study treatment and/or before the intitiation of any new cancer treatment. The patient was then followed up for survival every 3 months after the last study treatment dose until death, lost to follow-up, withdrawal of consent or until all patients completed at least 9 months of follow-up.

Reporting group title

Gastric Carcinoma Cohort

Reporting group description

Patients with advanced or metastatic gastric carcinoma after one line of platinum-containing therapy were administered a starting dose of tasquinimod 0.5 mg/day for at least 2 weeks. After at least 2 weeks the dose was adjusted depending on individual safety and tolerability to be either increased to 1 mg/day, reduced to 0.25 mg/day or maintained at 0.5 mg/day. Patients continued to receive daily oral doses of tasquinimod 0.25, 0.5 or 1.0 mg/day until disease progression, lost to follow-up, withdrawal or death. An end of study/withdrawal visit was performed at least 14 days after the last dose of study treatment and/or before the intitiation of any new cancer treatment. The patient was then followed up for survival every 3 months after the last study treatment dose until death, lost to follow-up, withdrawal of consent or until all patients completed at least 9 months of follow-up.

Serious adverse events	Hepatocellular Carcinoma Cohort	Ovarian Carcinoma Cohort	Renal Cell Carcinoma	Gastric Carcinoma Cohort
Total subjects affected by serious adverse events
subjects affected / exposed	14 / 53 (26.42%)	19 / 55 (34.55%)	11 / 38 (28.95%)	7 / 21 (33.33%)
number of deaths (all causes)	38	22	22	16
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Inflammatory myofibroblastic tumour
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metastatic pain
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tumour pain
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	2 / 53 (3.77%)	0 / 55 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Disease progression
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pleural effusion
subjects affected / exposed	0 / 53 (0.00%)	4 / 55 (7.27%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cough
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pleuritic pain
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood bilirubin increased
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Humerus fracture
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Myocardial infarction
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Hepatic encephalopathy
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ataxia
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dizziness
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Partial seizures
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 53 (3.77%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Nausea
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	0 / 38 (0.00%)	2 / 21 (9.52%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 53 (1.89%)	1 / 55 (1.82%)	0 / 38 (0.00%)	2 / 21 (9.52%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 53 (0.00%)	2 / 55 (3.64%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower gastrointestinal haemorrhage
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal varices haemorrhage
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ascites
subjects affected / exposed	1 / 53 (1.89%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subileus
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Bile duct obstruction
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disease
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure acute
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
Musculoskeletal and connective tissue disorders
Flank pain
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pathological fracture
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Cellulitis
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	0 / 38 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	2 / 53 (3.77%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infectious pleural effusion
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung infection
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic infection
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pleural infection
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal candidiasis
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oral candidiasis
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Decreased appetite
subjects affected / exposed	2 / 53 (3.77%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Iron deficiency
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Hepatocellular Carcinoma Cohort	Ovarian Carcinoma Cohort	Renal Cell Carcinoma	Gastric Carcinoma Cohort
Total subjects affected by non serious adverse events
subjects affected / exposed	53 / 53 (100.00%)	55 / 55 (100.00%)	38 / 38 (100.00%)	21 / 21 (100.00%)
Vascular disorders
Orthostatic hypotension
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	2 / 21 (9.52%)
occurrences all number	0	0	1	2
Hypertension
subjects affected / exposed	3 / 53 (5.66%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	4	0	0	0
Hypotension
subjects affected / exposed	1 / 53 (1.89%)	1 / 55 (1.82%)	5 / 38 (13.16%)	1 / 21 (4.76%)
occurrences all number	1	1	5	2
General disorders and administration site conditions
Oedema peripheral
subjects affected / exposed	16 / 53 (30.19%)	17 / 55 (30.91%)	4 / 38 (10.53%)	2 / 21 (9.52%)
occurrences all number	18	21	9	2
Fatigue
subjects affected / exposed	31 / 53 (58.49%)	31 / 55 (56.36%)	7 / 38 (18.42%)	15 / 21 (71.43%)
occurrences all number	36	41	7	18
Asthenia
subjects affected / exposed	7 / 53 (13.21%)	5 / 55 (9.09%)	11 / 38 (28.95%)	0 / 21 (0.00%)
occurrences all number	8	7	17	0
Pyrexia
subjects affected / exposed	2 / 53 (3.77%)	8 / 55 (14.55%)	1 / 38 (2.63%)	1 / 21 (4.76%)
occurrences all number	4	10	1	1
Chest pain
subjects affected / exposed	1 / 53 (1.89%)	0 / 55 (0.00%)	2 / 38 (5.26%)	0 / 21 (0.00%)
occurrences all number	1	0	2	0
Chills
subjects affected / exposed	0 / 53 (0.00%)	2 / 55 (3.64%)	2 / 38 (5.26%)	1 / 21 (4.76%)
occurrences all number	0	2	2	1
Influenza like illness
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	2 / 38 (5.26%)	0 / 21 (0.00%)
occurrences all number	0	0	2	0
Reproductive system and breast disorders
Pelvic pain
subjects affected / exposed	1 / 53 (1.89%)	3 / 55 (5.45%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	3	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	5 / 53 (9.43%)	12 / 55 (21.82%)	9 / 38 (23.68%)	3 / 21 (14.29%)
occurrences all number	5	12	10	3
Dyspnoea
subjects affected / exposed	10 / 53 (18.87%)	12 / 55 (21.82%)	3 / 38 (7.89%)	1 / 21 (4.76%)
occurrences all number	12	13	3	1
Pleural effusion
subjects affected / exposed	1 / 53 (1.89%)	2 / 55 (3.64%)	2 / 38 (5.26%)	0 / 21 (0.00%)
occurrences all number	1	2	2	0
Dyspnoea exertional
subjects affected / exposed	0 / 53 (0.00%)	3 / 55 (5.45%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	3	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	9 / 53 (16.98%)	9 / 55 (16.36%)	6 / 38 (15.79%)	6 / 21 (28.57%)
occurrences all number	11	10	6	6
Investigations
Weight decreased
subjects affected / exposed	13 / 53 (24.53%)	3 / 55 (5.45%)	5 / 38 (13.16%)	6 / 21 (28.57%)
occurrences all number	14	3	5	6
Blood alkaline phosphatase increased
subjects affected / exposed	1 / 53 (1.89%)	4 / 55 (7.27%)	1 / 38 (2.63%)	3 / 21 (14.29%)
occurrences all number	1	4	1	3
Alanine aminotransferase increased
subjects affected / exposed	3 / 53 (5.66%)	6 / 55 (10.91%)	0 / 38 (0.00%)	2 / 21 (9.52%)
occurrences all number	3	7	0	3
Aspartate aminotransferase increased
subjects affected / exposed	4 / 53 (7.55%)	6 / 55 (10.91%)	1 / 38 (2.63%)	2 / 21 (9.52%)
occurrences all number	4	7	1	2
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	0 / 38 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	0	0	2
Blood bilirubin increased
subjects affected / exposed	4 / 53 (7.55%)	2 / 55 (3.64%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	4	2	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 53 (1.89%)	5 / 55 (9.09%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences all number	1	5	1	0
Lipase increased
subjects affected / exposed	0 / 53 (0.00%)	6 / 55 (10.91%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	6	0	0
Amylase increased
subjects affected / exposed	0 / 53 (0.00%)	5 / 55 (9.09%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	5	0	0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 53 (0.00%)	4 / 55 (7.27%)	0 / 38 (0.00%)	3 / 21 (14.29%)
occurrences all number	0	5	0	4
Cardiac disorders
Sinus tachycardia
subjects affected / exposed	0 / 53 (0.00%)	3 / 55 (5.45%)	0 / 38 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	3	0	1
Nervous system disorders
Headache
subjects affected / exposed	9 / 53 (16.98%)	10 / 55 (18.18%)	4 / 38 (10.53%)	1 / 21 (4.76%)
occurrences all number	9	13	4	1
Peripheral sensory neuropathy
subjects affected / exposed	4 / 53 (7.55%)	2 / 55 (3.64%)	2 / 38 (5.26%)	1 / 21 (4.76%)
occurrences all number	4	2	2	1
Dizziness
subjects affected / exposed	2 / 53 (3.77%)	5 / 55 (9.09%)	4 / 38 (10.53%)	1 / 21 (4.76%)
occurrences all number	2	5	5	1
Amnesia
subjects affected / exposed	0 / 53 (0.00%)	3 / 55 (5.45%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	3	0	0
Lethargy
subjects affected / exposed	0 / 53 (0.00%)	2 / 55 (3.64%)	5 / 38 (13.16%)	1 / 21 (4.76%)
occurrences all number	0	2	5	1
Dysgeusia
subjects affected / exposed	1 / 53 (1.89%)	1 / 55 (1.82%)	2 / 38 (5.26%)	0 / 21 (0.00%)
occurrences all number	1	1	2	0
Neuralgia
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	2 / 38 (5.26%)	0 / 21 (0.00%)
occurrences all number	0	0	2	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 53 (3.77%)	9 / 55 (16.36%)	3 / 38 (7.89%)	5 / 21 (23.81%)
occurrences all number	2	9	3	7
Eye disorders
Periorbital oedema
subjects affected / exposed	0 / 53 (0.00%)	4 / 55 (7.27%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	4	0	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	15 / 53 (28.30%)	19 / 55 (34.55%)	8 / 38 (21.05%)	9 / 21 (42.86%)
occurrences all number	17	20	8	11
Nausea
subjects affected / exposed	21 / 53 (39.62%)	24 / 55 (43.64%)	12 / 38 (31.58%)	13 / 21 (61.90%)
occurrences all number	28	30	13	17
Vomiting
subjects affected / exposed	18 / 53 (33.96%)	16 / 55 (29.09%)	9 / 38 (23.68%)	13 / 21 (61.90%)
occurrences all number	25	21	9	18
Constipation
subjects affected / exposed	15 / 53 (28.30%)	12 / 55 (21.82%)	13 / 38 (34.21%)	11 / 21 (52.38%)
occurrences all number	16	12	13	13
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	1 / 38 (2.63%)	5 / 21 (23.81%)
occurrences all number	0	1	2	6
Dyspepsia
subjects affected / exposed	0 / 53 (0.00%)	5 / 55 (9.09%)	2 / 38 (5.26%)	4 / 21 (19.05%)
occurrences all number	0	6	2	4
Diarrhoea
subjects affected / exposed	14 / 53 (26.42%)	14 / 55 (25.45%)	7 / 38 (18.42%)	3 / 21 (14.29%)
occurrences all number	20	18	8	3
Abdominal distension
subjects affected / exposed	4 / 53 (7.55%)	10 / 55 (18.18%)	1 / 38 (2.63%)	2 / 21 (9.52%)
occurrences all number	4	12	1	2
Abdominal pain upper
subjects affected / exposed	7 / 53 (13.21%)	13 / 55 (23.64%)	1 / 38 (2.63%)	2 / 21 (9.52%)
occurrences all number	9	14	1	2
Epigastric discomfort
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	0 / 38 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	0	0	2
Eructation
subjects affected / exposed	0 / 53 (0.00%)	1 / 55 (1.82%)	0 / 38 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	1	0	2
Retching
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	1 / 38 (2.63%)	2 / 21 (9.52%)
occurrences all number	0	0	1	4
Ascites
subjects affected / exposed	5 / 53 (9.43%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	8	0	0	0
Dysphagia
subjects affected / exposed	3 / 53 (5.66%)	1 / 55 (1.82%)	1 / 38 (2.63%)	1 / 21 (4.76%)
occurrences all number	4	1	2	1
Dry mouth
subjects affected / exposed	2 / 53 (3.77%)	3 / 55 (5.45%)	0 / 38 (0.00%)	1 / 21 (4.76%)
occurrences all number	2	3	0	1
Skin and subcutaneous tissue disorders
Dry skin
subjects affected / exposed	3 / 53 (5.66%)	1 / 55 (1.82%)	3 / 38 (7.89%)	1 / 21 (4.76%)
occurrences all number	3	1	3	1
Pruritus
subjects affected / exposed	2 / 53 (3.77%)	4 / 55 (7.27%)	3 / 38 (7.89%)	0 / 21 (0.00%)
occurrences all number	2	4	4	0
Rash
subjects affected / exposed	0 / 53 (0.00%)	4 / 55 (7.27%)	3 / 38 (7.89%)	0 / 21 (0.00%)
occurrences all number	0	5	3	0
Hyperhidrosis
subjects affected / exposed	0 / 53 (0.00%)	3 / 55 (5.45%)	3 / 38 (7.89%)	1 / 21 (4.76%)
occurrences all number	0	3	3	1
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 53 (0.00%)	2 / 55 (3.64%)	3 / 38 (7.89%)	0 / 21 (0.00%)
occurrences all number	0	2	3	0
Night sweats
subjects affected / exposed	1 / 53 (1.89%)	2 / 55 (3.64%)	2 / 38 (5.26%)	1 / 21 (4.76%)
occurrences all number	1	2	2	1
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	9 / 53 (16.98%)	14 / 55 (25.45%)	5 / 38 (13.16%)	11 / 21 (52.38%)
occurrences all number	11	15	6	12
Pain in extremity
subjects affected / exposed	4 / 53 (7.55%)	5 / 55 (9.09%)	4 / 38 (10.53%)	4 / 21 (19.05%)
occurrences all number	6	6	6	5
Flank pain
subjects affected / exposed	2 / 53 (3.77%)	2 / 55 (3.64%)	1 / 38 (2.63%)	2 / 21 (9.52%)
occurrences all number	3	2	1	2
Arthralgia
subjects affected / exposed	5 / 53 (9.43%)	10 / 55 (18.18%)	2 / 38 (5.26%)	3 / 21 (14.29%)
occurrences all number	8	11	3	5
Musculoskeletal pain
subjects affected / exposed	3 / 53 (5.66%)	4 / 55 (7.27%)	4 / 38 (10.53%)	2 / 21 (9.52%)
occurrences all number	4	5	6	2
Myalgia
subjects affected / exposed	2 / 53 (3.77%)	6 / 55 (10.91%)	4 / 38 (10.53%)	2 / 21 (9.52%)
occurrences all number	3	6	4	2
Bone pain
subjects affected / exposed	4 / 53 (7.55%)	2 / 55 (3.64%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	4	2	0	0
Neck pain
subjects affected / exposed	3 / 53 (5.66%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	3	0	0	0
Muscular weakness
subjects affected / exposed	1 / 53 (1.89%)	3 / 55 (5.45%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences all number	1	3	1	0
Infections and infestations
Lower respiratory tract infection
subjects affected / exposed	0 / 53 (0.00%)	0 / 55 (0.00%)	5 / 38 (13.16%)	3 / 21 (14.29%)
occurrences all number	0	0	6	3
Oral candidiasis
subjects affected / exposed	1 / 53 (1.89%)	2 / 55 (3.64%)	0 / 38 (0.00%)	3 / 21 (14.29%)
occurrences all number	1	2	0	4
Urinary tract infection
subjects affected / exposed	1 / 53 (1.89%)	7 / 55 (12.73%)	0 / 38 (0.00%)	2 / 21 (9.52%)
occurrences all number	1	7	0	3
Rash pustular
subjects affected / exposed	4 / 53 (7.55%)	0 / 55 (0.00%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	4	0	0	0
Bronchitis
subjects affected / exposed	3 / 53 (5.66%)	0 / 55 (0.00%)	1 / 38 (2.63%)	0 / 21 (0.00%)
occurrences all number	3	0	1	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	21 / 53 (39.62%)	20 / 55 (36.36%)	11 / 38 (28.95%)	15 / 21 (71.43%)
occurrences all number	22	25	11	17
Hyponatraemia
subjects affected / exposed	1 / 53 (1.89%)	3 / 55 (5.45%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	2	3	0	0
Hypercalcaemia
subjects affected / exposed	0 / 53 (0.00%)	3 / 55 (5.45%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	3	0	0
Hypokalaemia
subjects affected / exposed	1 / 53 (1.89%)	3 / 55 (5.45%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	3	0	0
Hypoalbuminaemia
subjects affected / exposed	2 / 53 (3.77%)	6 / 55 (10.91%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	3	6	0	0
Hyperglycaemia
subjects affected / exposed	0 / 53 (0.00%)	4 / 55 (7.27%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	5	0	0
Hypomagnesaemia
subjects affected / exposed	0 / 53 (0.00%)	4 / 55 (7.27%)	0 / 38 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	4	0	1
Glucose tolerance impaired
subjects affected / exposed	0 / 53 (0.00%)	3 / 55 (5.45%)	0 / 38 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	3	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

11 Jan 2013

• The primary endpoint for the Hepatocellular Carcinoma cohort was amended to clarify that the assessment of PFS was based on RECIST criteria only and the PFS evaluation by Choi criteria was changed from a primary to a secondary endpoint. • Additional text was included to clarify that all the secondary efficacy endpoints will be reported based on the central evaluation (sensitivity analyses were based on the local evaluation). • Text was also added to clarify the reporting of TEAEs during the follow-up period and that the tumour assessments should continue to be performed during the follow-up period if the reason for tasquinimod discontinuation is not PD. • The addition of disallowed foods to Appendix 6 occurred due to their inhibitory effect on the activity of Cytochrome P450 3A4. • The addition of a new appendix (Appendix 7) on blood sample processing for biobanking at the request of the French Ethics Committee.

22 May 2015

• Following the results of the 10TASQ10 study (EudraCT number 2010-021870-12, sponsored by Active Biotech), Ipsen decided to discontinue the development of tasquinimod in all indications. Although the 10TASQ10 study showed that tasquinimod reduced the risk of radiographic cancer progression or death compared to placebo in patients with metastatic castration resistant prostate cancer (mCRPC) who have not received chemotherapy, treatment with tasquinimod did not extend overall survival. Efficacy results together with preliminary safety data do not support positive benefit risk balance in this population. In this (8-55-58102-004), which evaluated other indications, the clinical activity of tasquinimod in heavily pre-treated patients with advanced ovarian, renal cell, liver and gastric carcinomas was not demonstrated. Three ongoing patients at the time of this Protocol Amendment were offered to continue receiving tasquinimod if they had clinical benefit. • Discontinuation of follow-up all patients beyond 14 days after the last tasquinimod dose. • Removal of exploratory assessments (inflammatory and exploratory markers) and survival follow-up from 4 May 2015 onwards. • Collection of only treatment administration information, TEAEs and SAEs for 3 patients still under treatment.

Were there any global interruptions to the trial? No

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

This study consisted of an active treatment phase and a survival follow-up phase. All results data are presented according to the final analysis cut-off date for the active phase. Follow-up was stopped as described in protocol amendment 22 May 2015.

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
A Multicentre, Open-Label, Early Stopping Design, Proof of Concept Study with Tasquinimod in Treating Patients with Advanced or Metastatic Hepatocellular, Ovarian, Renal Cell and Gastric Carcinomas

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: PFS Rate based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) Criteria (All Cohorts)

Primary: PFS Rate based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) Criteria (All Cohorts)

Secondary: PFS Rate measured by the Choi criteria (Hepatocellular Carcinoma Cohort)

Secondary: PFS Rate measured by the Choi criteria (Hepatocellular Carcinoma Cohort)

Secondary: Best Overall Response and Response Rates using RECIST v1.1 for (All Cohorts)

Secondary: Best Overall Response and Response Rates using RECIST v1.1 for (All Cohorts)

Secondary: Best Overall Response and Response Rates using Choi criteria (Hepatocellular Carcinoma Cohort)

Secondary: Best Overall Response and Response Rates using Choi criteria (Hepatocellular Carcinoma Cohort)

Secondary: Clinical Benefit according to RECIST v1.1 (All Cohorts)

Secondary: Clinical Benefit according to RECIST v1.1 (All Cohorts)

Secondary: Median PFS from First Study Treatment to Progression or death due to any cause (Hepatocellular Carcinoma Cohort)

Secondary: Median PFS from First Study Treatment to Progression or death due to any cause (Hepatocellular Carcinoma Cohort)

Secondary: Median PFS from first study treatment to progression or death due to any cause using RECIST v1.1 criteria (All Cohorts)

Secondary: Median PFS from first study treatment to progression or death due to any cause using RECIST v1.1 criteria (All Cohorts)

Secondary: Time to Progression (TTP) using the Choi criteria (Hepatocellular Carcinoma Cohort)

Secondary: Time to Progression (TTP) using the Choi criteria (Hepatocellular Carcinoma Cohort)

Secondary: TTP using RECIST v1.1 criteria (All Cohorts)

Secondary: TTP using RECIST v1.1 criteria (All Cohorts)

Secondary: Overall Survival (OS) from first study treatment to death due to any cause (All Cohorts)

Secondary: Overall Survival (OS) from first study treatment to death due to any cause (All Cohorts)

Secondary: Further cancer-related treatment during the follow-up period for (All Cohorts)

Secondary: Further cancer-related treatment during the follow-up period for (All Cohorts)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Multicentre, Open-Label, Early Stopping Design, Proof of Concept Study with Tasquinimod in Treating Patients with Advanced or Metastatic Hepatocellular, Ovarian, Renal Cell and Gastric Carcinomas

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: PFS Rate based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) Criteria (All Cohorts)

Primary: PFS Rate based on Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) Criteria (All Cohorts)

Secondary: PFS Rate measured by the Choi criteria (Hepatocellular Carcinoma Cohort)

Secondary: PFS Rate measured by the Choi criteria (Hepatocellular Carcinoma Cohort)

Secondary: Best Overall Response and Response Rates using RECIST v1.1 for (All Cohorts)

Secondary: Best Overall Response and Response Rates using RECIST v1.1 for (All Cohorts)

Secondary: Best Overall Response and Response Rates using Choi criteria (Hepatocellular Carcinoma Cohort)

Secondary: Best Overall Response and Response Rates using Choi criteria (Hepatocellular Carcinoma Cohort)

Secondary: Clinical Benefit according to RECIST v1.1 (All Cohorts)

Secondary: Clinical Benefit according to RECIST v1.1 (All Cohorts)

Secondary: Median PFS from First Study Treatment to Progression or death due to any cause (Hepatocellular Carcinoma Cohort)

Secondary: Median PFS from First Study Treatment to Progression or death due to any cause (Hepatocellular Carcinoma Cohort)

Secondary: Median PFS from first study treatment to progression or death due to any cause using RECIST v1.1 criteria (All Cohorts)

Secondary: Median PFS from first study treatment to progression or death due to any cause using RECIST v1.1 criteria (All Cohorts)

Secondary: Time to Progression (TTP) using the Choi criteria (Hepatocellular Carcinoma Cohort)

Secondary: Time to Progression (TTP) using the Choi criteria (Hepatocellular Carcinoma Cohort)

Secondary: TTP using RECIST v1.1 criteria (All Cohorts)

Secondary: TTP using RECIST v1.1 criteria (All Cohorts)

Secondary: Overall Survival (OS) from first study treatment to death due to any cause (All Cohorts)

Secondary: Overall Survival (OS) from first study treatment to death due to any cause (All Cohorts)

Secondary: Further cancer-related treatment during the follow-up period for (All Cohorts)

Secondary: Further cancer-related treatment during the follow-up period for (All Cohorts)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Multicentre, Open-Label, Early Stopping Design, Proof of Concept Study with Tasquinimod in Treating Patients with Advanced or Metastatic Hepatocellular, Ovarian, Renal Cell and Gastric Carcinomas