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Clinical Trial Results:
Phase IB-II, open label, multicentre feasibility study of pazopanib in combination with Paclitaxel and Carboplatin in patients with platinumrefractory/ resistant ovarian, fallopian tube or peritoneal carcinoma.

Summary
EudraCT number	2010-024077-39
Trial protocol	BE NL ES
Global end of trial date	13 Jul 2020

Results information
Results version number	v1(current)
This version publication date	28 Aug 2022
First version publication date	28 Aug 2022
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

55092

ISRCTN number

US NCT number

NCT01402271

WHO universal trial number (UTN)

Sponsor organisation name

EORTC

Sponsor organisation address

Avenue E. Mounier 83/11, Brussels, Belgium, 1200

Public contact

Head Clinical Operations Dpt, European Organisation for Research and Treatment of Cancer, 0032 27741015, eortc@eortc.org

Scientific contact

Head Clinical Operations Dpt, European Organisation for Research and Treatment of Cancer, 0032 27741015, eortc@eortc.org

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

13 Jul 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

13 Jul 2020

Global end of trial reached?

Yes

Global end of trial date

13 Jul 2020

Was the trial ended prematurely?

Main objective of the trial

Determine the activity measured by progression free survival (PFS) according to the RECIST 1.1 of the combination of Pazopanib with weekly paclitaxel and carboplatin in platinum resistant ovarian, fallopian tube or peritoneal carcinoma at the optimum dose established in the phase I part.

Protection of trial subjects

The study is conducted in agreement with the Declaration of Helsinki (available on the World Medical Association web site (http://www.wma.net)) and/or the laws and regulations of the participating countries, whichever provides the greatest protection of the patient. The protocol has been written, and the study conducted according to the ICH Harmonized Tripartite Guideline on Good Clinical Practice. The protocol was approved by the competent ethics committee(s) as required by the applicable national legislation. Safety data were reviewed within the EORTC Headquarters on a regular basis as part of the Medical Review process. Safety information was included in trial status reports which served as a basis of discussion during EORTC Group meetings.

Background therapy

Standard arm: According to institutional policies and patient's history: • Scheme 1: paclitaxel weekly at a dose of 80 mg/m² for 18 courses • Scheme 2: paclitaxel weekly at a dose of 80 mg/m² for 18 courses combined with bevacizumab at a dose of 15 mg/kg 3 weekly • Scheme 3: paclitaxel weekly at a dose of 60mg/m² for 18 courses combined with carboplatin at an AUC of 2.7 weekly for 18 courses Experimental arm: carboplatin AUC 2.0 weekly and paclitaxel 30 mg/m² weekly and Pazopanib 400 mg daily for 18 courses.

Evidence for comparator

Several phase I/II studies were conducted previously with promising results. Du Bois et al (duBois A, Floquet A, Kim J, et al. Randomized, double-blind, phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): results of an international Intergroup trial (AGO-OVAR16). Am Soc Clin Oncol. 2013;31 Suppl:LBA5503), presented the results of the AGO-OVAR-16 study of maintenance pazopanib in women with advanced newly diagnosed EOC. The trial was a double-blinded, multicenter Phase III study that randomized 940 women with advanced-stage EOC, FTC, or PPC to receive maintenance pazopanib versus placebo for 24 months. All patients had previously achieved a clinical response with first-line platinum-based therapy. Median PFS was significantly longer in the pazopanib group (17.9 versus 12.3, HR 0.77, 95% CI 0.64–0.91, P=0.0021). Angiogenesis and especially targeting VEGF has been shown to be very interesting in gynaecological cancer. In preclinical models of ovarian cancer, anti-VEGF therapy has been shown to inhibit ascites formation, slow tumor growth and synergy with cytotoxic agents.

Actual start date of recruitment

01 Nov 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 48

Country: Number of subjects enrolled

Spain: 9

Country: Number of subjects enrolled

Belgium: 31

Worldwide total number of subjects

EEA total number of subjects

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

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Recruitment details

The phase Ib part of the trial enrolled 28 patients by 3 centers from 3 countries (Netherlands, Belgium, Spain) between 24/08/2012.and 22/01/2014 across 4 different dose levels. Between 26 May 2015 and 15 May 2018, 60 patients were randomized by 7 centers from 3 countries (Netherlands, Belgium, Spain) in the phase II part.

Screening details

Phase II: Histologically confirmed ovarian, fallopian tube, or peritoneal carcinoma with recurrent disease. At least one earlier platinum treatment can be included but should be platinum-resistant. Non-platinum treatment after proven platinum resistance disease is allowed. Evaluable disease by RECIST v. 1.1. WHO Performance status must be ≤ 2.

Period 1 title

Over all study period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Recruitment into dose levels occurs by allocation to the open dose level cohort in the phase Ib part. In the phase II part, patients are centrally randomized using a minimization technique for random treatment allocation stratifying by institution, number of prior lines (one vs more than one), WHO performance status (0/1 vs 2). The randomization has a 2:1 ratio with double the number of patients in the experimental arm.

Are arms mutually exclusive

Yes

Standard arm

Arm description

According to institutional policies and patient's history, the patient can receive: • Scheme 1: paclitaxel weekly at a dose of 80 mg/m² for 18 courses • Scheme 2: paclitaxel weekly at a dose of 80 mg/m² for 18 courses combined with bevacizumab at a dose of 15 mg/kg 3 weekly • Scheme 3: paclitaxel weekly at a dose of 60mg/m² for 18 courses combined with carboplatin at an AUC of 2.7 weekly for 18 courses

Arm type

standard of care

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Experimental arm

Arm description

Carboplatin AUC 2.0 weekly and paclitaxel 30 mg/m² weekly and Pazopanib 400 mg daily for 18 courses. Patients can continue pazopanib (at the standard dose of 800 mg per day) after the planned 18 courses of paclitaxel-carboplatin weekly until documented disease progression, unacceptable toxicity or patient refusal.

Arm type

Experimental

Investigational medicinal product name

Pazopanib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Pazopanib 400mg will be given daily orally. Pazopanib will not be administered on the day paclitaxel and carboplatin is administered. Between last pazopanib dose and start of the chemotherapy administration, and also between the end of chemotherapy administration and the next pazopanib dose a period of 24 hours should elapse. Pazopanib will be continued at a dose of 400 mg per day after the last paclitaxel-carboplatin dose, and escalated at the standard dose of 800 mg per day 2 - 4 weeks after the last paclitaxel-carboplatin dose until documented disease progression, unacceptable toxicity or patient refusal.

Dose level 1

Arm description

Paclitaxel 30 mg/m² weekly; Carboplatin 1.5 AUC weekly; Pazopanib 400 mg daily

Arm type

Dose level

Investigational medicinal product name

Pazopanib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Dose level 2

Arm description

Paclitaxel 30 mg/m² weekly; Carboplatin 2.0 AUC weekly; Pazopanib 400 mg daily.

Arm type

Dose level

Investigational medicinal product name

Pazopanib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Dose level 3

Arm description

Paclitaxel 30 mg/m² weekly; Carboplatin 2.0 AUC weekly; Pazopanib 800 mg daily

Arm type

Dose level

Investigational medicinal product name

Pazopanib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Pazopanib 800mg will be given daily orally. Pazopanib will not be administered on the day paclitaxel and carboplatin is administered. Between last pazopanib dose and start of the chemotherapy administration, and also between the end of chemotherapy administration and the next pazopanib dose a period of 24 hours should elapse. Pazopanib will be continued at a dose of 800 mg per day after the last paclitaxel-carboplatin dose, and 2 - 4 weeks after the last paclitaxel-carboplatin dose until documented disease progression, unacceptable toxicity or patient refusal.

Dose level 7

Arm description

Paclitaxel 30 mg/m² weekly; Carboplatin 2.0 AUC weekly; Pazopanib 600 mg daily

Arm type

Dose level

Investigational medicinal product name

Pazopanib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Pazopanib 600mg will be given daily orally. Pazopanib will not be administered on the day paclitaxel and carboplatin is administered. Between last pazopanib dose and start of the chemotherapy administration, and also between the end of chemotherapy administration and the next pazopanib dose a period of 24 hours should elapse. Pazopanib will be continued at a dose of 600 mg per day after the last paclitaxel-carboplatin dose, and escalated at the standard dose of 800 mg per day 2 - 4 weeks after the last paclitaxel-carboplatin dose until documented disease progression, unacceptable toxicity or patient refusal.

Number of subjects in period 1	Standard arm	Experimental arm	Dose level 1	Dose level 2	Dose level 3	Dose level 7
Started	21	39	8	6	7	7
Completed	9	14	6	5	6	6
Not completed	12	25	2	1	1	1
Consent withdrawn by subject	1	1	-	-	-	-
Physician decision	1	-	-	-	-	-
chemotherapy not started due to pleural empyema	-	-	-	1	-	-
Adverse event, non-fatal	3	10	-	-	-	-
progressive disease	7	13	-	-	-	-
clinical deterioration	-	1	-	-	-	-
Protocol deviation	-	-	2	-	1	1

Baseline characteristics

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Reporting group title

Standard arm

Reporting group description

Reporting group title

Experimental arm

Reporting group description

Reporting group title

Dose level 1

Reporting group description

Paclitaxel 30 mg/m² weekly; Carboplatin 1.5 AUC weekly; Pazopanib 400 mg daily

Reporting group title

Dose level 2

Reporting group description

Paclitaxel 30 mg/m² weekly; Carboplatin 2.0 AUC weekly; Pazopanib 400 mg daily.

Reporting group title

Dose level 3

Reporting group description

Paclitaxel 30 mg/m² weekly; Carboplatin 2.0 AUC weekly; Pazopanib 800 mg daily

Reporting group title

Dose level 7

Reporting group description

Paclitaxel 30 mg/m² weekly; Carboplatin 2.0 AUC weekly; Pazopanib 600 mg daily

Reporting group values	Standard arm	Experimental arm	Dose level 1	Dose level 2	Dose level 3	Dose level 7	Total
Number of subjects	21	39	8	6	7	7	88
Age categorical
Units: Subjects
Adults (18-64 years)	13	16	6	1	4	4	44
From 65-84 years	8	22	2	5	3	3	43
85 years and over	0	1	0	0	0	0	1
Age continuous
Units: years
median (inter-quartile range (Q1-Q3))	60.9 (53.8 to 68.7)	66.4 (57.7 to 72.1)	59.7 (52.6 to 64.4)	65.7 (65.0 to 66.6)	63.9 (55.2 to 66.4)	63.4 (49.2 to 67.7)	-
Gender categorical
Units: Subjects
Female	21	39	8	6	7	7	88
Male	0	0	0	0	0	0	0
WHO PS
WHO performance status
Units: Subjects
PS 0	5	20	4	1	1	2	33
PS 1	14	18	4	5	6	5	52
PS 2	2	1	0	0	0	0	3
Tumor grade
Units: Subjects
Well differentiated	2	4	3	3	1	3	16
Moderately differentiated	3	0	1	0	2	0	6
Poorly differentiated	15	27	1	3	3	2	51
Unknown	1	8	3	0	1	2	15
Histology
Units: Subjects
Serous	17	33	5	4	6	3	68
Clear cell	1	3	2	0	0	1	7
Endometroid	1	1	0	0	0	1	3
Undifferentiated	1	1	0	1	0	0	3
Other/mixed	1	1	1	1	1	2	7
number of prior lines
Units: Subjects
one	4	6	0	1	1	1	13
more than one	17	33	8	5	6	6	75
Time since initial diagnosis
Units: months
median (inter-quartile range (Q1-Q3))	25.9 (17.3 to 41.5)	38.1 (18.7 to 54.3)	26.7 (14.9 to 55.9)	27.6 (12.1 to 39.3)	36.3 (25.1 to 71.7)	31.8 (25.7 to 53.2)	-
Time since last platinum based chemotherapy
Units: weeks
median (inter-quartile range (Q1-Q3))	25.1 (19.3 to 43.6)	25.9 (19.9 to 45.0)	23.9 (15.6 to 31.1)	34.0 (29.4 to 40.1)	18.4 (10.1 to 30.0)	28.2 (15.6 to 34.9)	-

End points

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Reporting group title

Standard arm

Reporting group description

Reporting group title

Experimental arm

Reporting group description

Reporting group title

Dose level 1

Reporting group description

Paclitaxel 30 mg/m² weekly; Carboplatin 1.5 AUC weekly; Pazopanib 400 mg daily

Reporting group title

Dose level 2

Reporting group description

Paclitaxel 30 mg/m² weekly; Carboplatin 2.0 AUC weekly; Pazopanib 400 mg daily.

Reporting group title

Dose level 3

Reporting group description

Paclitaxel 30 mg/m² weekly; Carboplatin 2.0 AUC weekly; Pazopanib 800 mg daily

Reporting group title

Dose level 7

Reporting group description

Paclitaxel 30 mg/m² weekly; Carboplatin 2.0 AUC weekly; Pazopanib 600 mg daily

Primary: PFS at year 1

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End point title

PFS at year 1

End point description

Success is defined as alive and without confirmed progression at or after 1 year from randomization are considered a success. Patients who died or progressed before the 1 year mark will be considered as failures. Patients who are unevaluable for tumour assessment are considered as failures. If a patient was last without confirmed progression > 1 month before the 1 year mark and has a confirmed progression at the first post 1-year assessment, that patient is also considered a failure.

End point type

Primary

End point timeframe

Up to 1 year after randomization. Progression assessed via RECIST 1.1.

End point values	Standard arm	Experimental arm	Dose level 1	Dose level 2	Dose level 3	Dose level 7
Number of subjects analysed	21	39	0 ^[1]	0 ^[2]	0 ^[3]	0 ^[4]
Units: Subjects
Alive without PD	1	1
Dead/PD/NE	20	38

Notes
[1] - Arm used for dose level finding purpose only
[2] - Arm used for dose level finding purpose only
[3] - Arm used for dose level finding purpose only
[4] - Arm used for dose level finding purpose only

PFS difference at 1 year

Statistical analysis description

The decision rule states that in order to exclude a 10% 1-year PFS rate while accepting a 25 % rate, at least 7 patients out of 40 need to be alive and progression free at 1 year.

Comparison groups

Experimental arm v Standard arm

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

other ^[5]

Method

Parameter type

PFS % at year 1 in experimental arm

Point estimate

2.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

13.5

Notes
[5] - Although only 39 patients were enrolled in the experimental arm, the decision rule can still be evaluated. As this study reported only 1 such patient out of 39 enrolled in the experimental, the criteria for success can not be met.

Secondary: Best overall response

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End point title

Best overall response

End point description

Best response observed during the trial according to RECIST 1.1

End point type

Secondary

End point timeframe

Best response observed during the trial

End point values	Standard arm	Experimental arm	Dose level 1	Dose level 2	Dose level 3	Dose level 7
Number of subjects analysed	21	39	0 ^[6]	0 ^[7]	0 ^[8]	0 ^[9]
Units: Subjects
Partial Response	8	7
Stable Disease	6	20
Progressive Disease	7	9
Early death	0	2
Not evaluable	0	1

Notes
[6] - Arm used for dose level finding purpose only
[7] - Arm used for dose level finding purpose only
[8] - Arm used for dose level finding purpose only
[9] - Arm used for dose level finding purpose only

No statistical analyses for this end point

Secondary: Disease Control Rate

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End point title

Disease Control Rate

End point description

Proportion of patients who achieved a complete response , partial response or stable disease.

End point type

Secondary

End point timeframe

Based on best response observed during trial

End point values	Standard arm	Experimental arm	Dose level 1	Dose level 2	Dose level 3	Dose level 7
Number of subjects analysed	21	39	0 ^[10]	0 ^[11]	0 ^[12]	0 ^[13]
Units: Subjects
CR/PR/SD	14	27

Notes
[10] - Arm used for dose level finding purpose only
[11] - Arm used for dose level finding purpose only
[12] - Arm used for dose level finding purpose only
[13] - Arm used for dose level finding purpose only

No statistical analyses for this end point

Secondary: Progression free survival

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End point title

Progression free survival

End point description

Progression free survival will be defined as the time interval between the date of randomization and the date of disease progression or death (any cause), whichever comes first. If neither event has been observed, then the patient is censored at the date of the last follow-up examination.

End point type

Secondary

End point timeframe

Based on survival status and tumour response observed during the trial

End point values	Standard arm	Experimental arm	Dose level 1	Dose level 2	Dose level 3	Dose level 7
Number of subjects analysed	21	39	0 ^[14]	0 ^[15]	0 ^[16]	0 ^[17]
Units: months
median (confidence interval 95%)	6.5 (2.6 to 7.6)	4.9 (3.4 to 6.7)	( to )	( to )	( to )	( to )

Notes
[14] - Arm used for dose level finding purpose only
[15] - Arm used for dose level finding purpose only
[16] - Arm used for dose level finding purpose only
[17] - Arm used for dose level finding purpose only

No statistical analyses for this end point

Secondary: Overall survival

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End point title

Overall survival

End point description

Overall survival will be defined as the time interval between the date of randomization and the date of death. Patients who were still alive when last traced are censored at the date of the last follow-up.

End point type

Secondary

End point timeframe

Based on the survival status observed during the trial

End point values	Standard arm	Experimental arm	Dose level 1	Dose level 2	Dose level 3	Dose level 7
Number of subjects analysed	21	39	0 ^[18]	0 ^[19]	0 ^[20]	0 ^[21]
Units: months
median (confidence interval 95%)	11.2 (5.7 to 13.5)	11.5 (6.1 to 15.5)	( to )	( to )	( to )	( to )

Notes
[18] - Arm used for dose level finding purpose only
[19] - Arm used for dose level finding purpose only
[20] - Arm used for dose level finding purpose only
[21] - Arm used for dose level finding purpose only

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events were recorded as they occur and graded according to the CTCAE version 4.0 from time of enrollment until 30 days after last protocol treatment or if deemed related to study participation.

Adverse event reporting additional description

AEs are evaluated using CTCAE v4 grading, SAEs using MedDra. AEs were also derived from laboratory toxicities if grade ≥3 and all laboratory toxicities that triggered a treatment modification, if not reported on an AE form, were added.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Standard arm

Reporting group description

Standard arm

Reporting group title

Experimental arm

Reporting group description

Experimental arm

Serious adverse events	Standard arm	Experimental arm
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 21 (33.33%)	15 / 39 (38.46%)
number of deaths (all causes)	20	32
number of deaths resulting from adverse events	0	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
ASPARTATE AMINOTRANSFERASE INCREASED
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
GAMMA-GLUTAMYLTRANSFERASE INCREASED
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
INFUSION RELATED REACTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
COMPRESSION FRACTURE
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (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
ANAEMIA
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	1 / 1
PANCYTOPENIA
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
FEBRILE NEUTROPENIA
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
THROMBOCYTOPENIA
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	3 / 39 (7.69%)
occurrences causally related to treatment / all	0 / 0	3 / 3
deaths causally related to treatment / all	0 / 0	1 / 1
General disorders and administration site conditions
ASTHENIA
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
MALAISE
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
PYREXIA
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
ENTEROCUTANEOUS FISTULA
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
CONSTIPATION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
ASCITES
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
ILEUS
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
INTESTINAL OBSTRUCTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
INTESTINAL PSEUDO-OBSTRUCTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
LARGE INTESTINAL OBSTRUCTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
NAUSEA
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
VOMITING
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
FEMALE GENITAL TRACT FISTULA
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
DYSPNOEA EXERTIONAL
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
INTERSTITIAL LUNG DISEASE
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
PULMONARY EMBOLISM
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 21 (4.76%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
HYDRONEPHROSIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
RENAL FAILURE
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Infections and infestations
BACTERAEMIA
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
CELLULITIS
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
PNEUMONIA
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 21 (4.76%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
INFECTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
GROIN ABSCESS
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
RESPIRATORY TRACT INFECTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
URINARY TRACT INFECTION
alternative dictionary used: MedDRA 24
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	Standard arm	Experimental arm
Total subjects affected by non serious adverse events
subjects affected / exposed	21 / 21 (100.00%)	39 / 39 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOR PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 21 (19.05%)	8 / 39 (20.51%)
occurrences all number	8	11
Vascular disorders
FLUSHING
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	3
HEMATOMA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	1 / 39 (2.56%)
occurrences all number	1	1
HOT FLASHES
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	3 / 39 (7.69%)
occurrences all number	0	3
LYMPHOCELE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	3	0
HYPOTENSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 21 (14.29%)	4 / 39 (10.26%)
occurrences all number	3	5
HYPERTENSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	6 / 21 (28.57%)	20 / 39 (51.28%)
occurrences all number	19	66
THROMBOEMBOLIC EVENT
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 21 (9.52%)	1 / 39 (2.56%)
occurrences all number	2	1
General disorders and administration site conditions
CHILLS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	3
EDEMA FACE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
EDEMA LIMBS
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 21 (9.52%)	8 / 39 (20.51%)
occurrences all number	2	10
FATIGUE
alternative dictionary used: CTCAE 4
subjects affected / exposed	13 / 21 (61.90%)	34 / 39 (87.18%)
occurrences all number	41	91
FEVER
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 21 (19.05%)	5 / 39 (12.82%)
occurrences all number	5	6
FLU LIKE SYMPTOMS
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 21 (19.05%)	9 / 39 (23.08%)
occurrences all number	6	14
GENERAL DISORDER
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
INFUSION RELATED REACTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	3	0
INFUSION SITE EXTRAVASATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
INJECTION SITE REACTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	1 / 39 (2.56%)
occurrences all number	2	3
INFUSION SITE REACTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
LOCALIZED EDEMA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
MALAISE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	2
PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	8 / 39 (20.51%)
occurrences all number	3	15
Immune system disorders
ALLERGIC REACTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	5 / 21 (23.81%)	6 / 39 (15.38%)
occurrences all number	9	8
AUTOIMMUNE DISORDER
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
CYTOKINE RELEASE SYNDROME
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
ANAPHYLAXIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
Reproductive system and breast disorders
VAGINAL HEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	4
Respiratory, thoracic and mediastinal disorders
ASPIRATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
COUGH
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 21 (19.05%)	9 / 39 (23.08%)
occurrences all number	8	11
DYSPNEA
alternative dictionary used: CTCAE 4
subjects affected / exposed	5 / 21 (23.81%)	18 / 39 (46.15%)
occurrences all number	8	24
HOARSENESS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
EPISTAXIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	7 / 21 (33.33%)	9 / 39 (23.08%)
occurrences all number	9	11
PLEURAL EFFUSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	3 / 39 (7.69%)
occurrences all number	0	5
PRODUCTIVE COUGH
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
VOICE ALTERATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	3 / 39 (7.69%)
occurrences all number	0	3
SORE THROAT
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	1 / 39 (2.56%)
occurrences all number	1	2
Psychiatric disorders
INSOMNIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	2 / 39 (5.13%)
occurrences all number	1	2
DEPRESSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	2 / 39 (5.13%)
occurrences all number	1	2
ANXIETY
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 21 (9.52%)	2 / 39 (5.13%)
occurrences all number	2	4
ALKALINE PHOSPHATASE INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	3
ALANINE AMINOTRANSFERASE INCREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 21 (9.52%)	3 / 39 (7.69%)
occurrences all number	2	3
NEUTROPHIL COUNT DECREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	6 / 21 (28.57%)	10 / 39 (25.64%)
occurrences all number	18	37
WHITE BLOOD CELL DECREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 21 (19.05%)	8 / 39 (20.51%)
occurrences all number	12	34
WEIGHT LOSS
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 21 (14.29%)	4 / 39 (10.26%)
occurrences all number	3	6
PLATELET COUNT DECREASED
alternative dictionary used: CTCAE 4
subjects affected / exposed	7 / 21 (33.33%)	11 / 39 (28.21%)
occurrences all number	23	40
Injury, poisoning and procedural complications
FRACTURE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	1 / 39 (2.56%)
occurrences all number	2	2
BRUISING
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
INJURY, POISONING AND PROCEDURAL COMPLICATIONS - SCAPE WOUND
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
RECTOVAGINAL FISTULA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
Cardiac disorders
PALPITATIONS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
HYPERTENSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
PERICARDIAL EFFUSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
Nervous system disorders
ATAXIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
DEPRESSED LEVEL OF CONSCIOUSNESS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	2
DIZZINESS
alternative dictionary used: CTCAE 4
subjects affected / exposed	6 / 21 (28.57%)	9 / 39 (23.08%)
occurrences all number	8	15
DYSESTHESIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
DYSGEUSIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	6 / 21 (28.57%)	11 / 39 (28.21%)
occurrences all number	6	11
SOMNOLENCE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
PERIPHERAL SENSORY NEUROPATHY
alternative dictionary used: CTCAE 4
subjects affected / exposed	8 / 21 (38.10%)	11 / 39 (28.21%)
occurrences all number	9	12
PARESTHESIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	2
SYNCOPE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
HEADACHE
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 21 (14.29%)	10 / 39 (25.64%)
occurrences all number	3	16
Blood and lymphatic system disorders
BLOOD AND LYMPHATIC SYSTEM DISORDER
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
ANEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	9 / 21 (42.86%)	14 / 39 (35.90%)
occurrences all number	28	36
FEBRILE NEUTROPENIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
Ear and labyrinth disorders
EAR PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	3	0
HEARING IMPAIRED
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	4 / 39 (10.26%)
occurrences all number	1	4
TINNITUS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	6 / 39 (15.38%)
occurrences all number	1	6
Eye disorders
BLURRED VISION
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 21 (14.29%)	7 / 39 (17.95%)
occurrences all number	3	8
DRY EYE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	2	0
CONJUNCTIVITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
EYE DISORDER OTHER: SLING IN THE EYE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
PHOTOPHOBIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
FLASHING LIGHTS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	2
VITREOUS HEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
RETINAL DETACHMENT
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	1 / 39 (2.56%)
occurrences all number	1	2
WATERING EYES
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	3 / 39 (7.69%)
occurrences all number	1	3
Gastrointestinal disorders
ABDOMINAL DISTENSION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	1 / 39 (2.56%)
occurrences all number	1	1
ANAL HEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	2
ABDOMINAL PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	5 / 21 (23.81%)	17 / 39 (43.59%)
occurrences all number	7	28
ASCITES
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	5 / 39 (12.82%)
occurrences all number	1	7
COLITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
BLOATING
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	1 / 39 (2.56%)
occurrences all number	1	1
COLONIC OBSTRUCTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	3
CONSTIPATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	9 / 21 (42.86%)	20 / 39 (51.28%)
occurrences all number	12	39
DIARRHEA
alternative dictionary used: CTCAE 4
subjects affected / exposed	7 / 21 (33.33%)	23 / 39 (58.97%)
occurrences all number	9	53
DRY MOUTH
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	2 / 39 (5.13%)
occurrences all number	5	2
DYSPEPSIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 21 (14.29%)	7 / 39 (17.95%)
occurrences all number	3	9
DYSPHAGIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
FLATULENCE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
ENTEROCUTANEOUS FISTULA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
LOWER GASTROINTESTINAL HEMORRHAGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
ILEUS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	4 / 39 (10.26%)
occurrences all number	0	7
GASTROINTESTINAL DISORDERS, OTHER - GASTRIC COMPLAINTS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
GASTROESOPHAGEAL REFLUX DISEASE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	2
MUCOSITIS ORAL
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 21 (14.29%)	7 / 39 (17.95%)
occurrences all number	13	10
NAUSEA
alternative dictionary used: CTCAE 4
subjects affected / exposed	18 / 21 (85.71%)	28 / 39 (71.79%)
occurrences all number	29	54
ORAL PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
PERIODONTAL DISEASE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
RECTAL ULCER
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	3	0
SMALL INTESTINAL OBSTRUCTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
VOMITING
alternative dictionary used: CTCAE 4
subjects affected / exposed	8 / 21 (38.10%)	15 / 39 (38.46%)
occurrences all number	18	27
TOOTHACHE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	3 / 39 (7.69%)
occurrences all number	0	3
STOMACH PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	3 / 39 (7.69%)
occurrences all number	1	3
Hepatobiliary disorders
HEPATIC PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
Skin and subcutaneous tissue disorders
ABSCESS GROIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
HYPERHIDROSIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	2
ALOPECIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	11 / 21 (52.38%)	8 / 39 (20.51%)
occurrences all number	18	8
DRY SKIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 21 (14.29%)	2 / 39 (5.13%)
occurrences all number	3	2
ERYTHEMA MULTIFORME
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
PAIN OF SKIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
NAIL RIDGING
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 21 (9.52%)	0 / 39 (0.00%)
occurrences all number	2	0
NAIL LOSS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	3	0
PALMAR-PLANTAR ERYTHRODYSESTHESIA SYNDROME
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	3 / 39 (7.69%)
occurrences all number	1	3
NAIL CHANGE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
RASH ACNEIFORM
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 21 (9.52%)	0 / 39 (0.00%)
occurrences all number	3	0
RASH
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	1 / 39 (2.56%)
occurrences all number	3	1
PRURITUS
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 21 (9.52%)	2 / 39 (5.13%)
occurrences all number	2	3
RASH MACULO-PAPULAR
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	4 / 39 (10.26%)
occurrences all number	1	4
SKIN AND SUBCUTANEOUS TISSUE DISORDER OTHER
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
SKIN AND SUBCUTANEOUS TISSUE DISORDERS OTHER
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
SKIN HYPOPIGMENTATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
SKIN RASH
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
SKIN ULCERATION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
Renal and urinary disorders
ACUTE KIDNEY INJURY
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	2
CYSTITIS NONINFECTIVE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	1 / 39 (2.56%)
occurrences all number	1	1
PROTEINURIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	5 / 39 (12.82%)
occurrences all number	1	10
HEMATURIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
RENAL AND URINARY DISORDERS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
RENAL AND URINARY DISORDERS - OTHER: DYSURIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
URINARY INCONTINENCE
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
URINARY FREQUENCY
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
URINARY TRACT PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
Endocrine disorders
CUSHINGOID
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
HYPOTHYROIDISM
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	3 / 39 (7.69%)
occurrences all number	0	3
ARTHRITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	3
BACK PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 21 (19.05%)	2 / 39 (5.13%)
occurrences all number	7	3
FLANK PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
GENERALIZED MUSCLE WEAKNESS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
MUSCLE WEAKNESS UPPER LIMB
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	2
MUSCULOSKELETAL - OTHER, SPECIFY; MUSCLE CRAMPS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER - OTHER,SPEC
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER - CRAMPS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER, OTHER CRAMP
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
MUSCULOSKELETAL/CONNECTIVE TISSUE DISORDER - OTHER STIFFNESS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
PAIN IN EXTREMITY
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	3 / 39 (7.69%)
occurrences all number	1	5
MYALGIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	3 / 21 (14.29%)	9 / 39 (23.08%)
occurrences all number	3	13
NECK PAIN
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
Infections and infestations
BLADDER INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 21 (9.52%)	3 / 39 (7.69%)
occurrences all number	2	6
CATHETER RELATED INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
NAIL INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	6
LUNG INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	3
INFECTIONS AND INFESTATIONS - OTHER: PULMONARY INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	2	0
EYE INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
PHARYNGITIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	2	0
SEPSIS
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	2 / 39 (5.13%)
occurrences all number	0	2
SKIN INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 21 (9.52%)	0 / 39 (0.00%)
occurrences all number	5	0
URINARY TRACT INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	4 / 21 (19.05%)	5 / 39 (12.82%)
occurrences all number	4	6
UPPER RESPIRATORY INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	2 / 21 (9.52%)	3 / 39 (7.69%)
occurrences all number	2	5
VAGINAL INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	1 / 39 (2.56%)
occurrences all number	1	1
WOUND INFECTION
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	0 / 39 (0.00%)
occurrences all number	1	0
Metabolism and nutrition disorders
ANOREXIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	8 / 21 (38.10%)	28 / 39 (71.79%)
occurrences all number	14	43
HYPERGLYCEMIA AND GLUCOSE INTOLERANCE
alternative dictionary used: CTCAE 4
subjects affected / exposed	0 / 21 (0.00%)	1 / 39 (2.56%)
occurrences all number	0	1
HYPOMAGNESEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	5 / 39 (12.82%)
occurrences all number	1	9
HYPOKALEMIA
alternative dictionary used: CTCAE 4
subjects affected / exposed	1 / 21 (4.76%)	2 / 39 (5.13%)
occurrences all number	1	3

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Were there any global substantial amendments to the protocol? Yes

02 Oct 2014

Substantial changes were made to accommodate the transition from phase Ib to phase II: - Change of inclusion criteria to exclude platinum refractory patients - Removal of all sections describing procedures applicable for the phase Ib part - Description of the results of the phase Ib part with the recommended dose level - Change of follow-up after end of chemotherapy of control arm and patients from the experimental arm that will go on Pazopanib maintenance treatment - Change of statistical analysis plan to remove the stratification according to platinum resistant versus refractory disease and to include stratification according to WHO performance status - Adaptation of PIS/IC.

26 Sep 2016

Based on the results of the AURELIA trial, changes in Standard arm have been introduced with possibility for the Principal Investigator to choose the standard treatment, according to institutional policies and patient's history, among : - paclitaxel weekly at a dose of 80 mg/m² for 18 courses - paclitaxel weekly at a dose of 80 mg/m² for 18 courses combined with bevacizumab at a dose of 15 mg/kg 3 weekly - paclitaxel weekly at a dose of 60mg/m² for 18 courses combined with carboplatin at an AUC of 2.7 weekly

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.

Posting of results is limited to the phase II part of the trial . The trial was amended after phase Ib to limit the patient population to resistant patients only despite the title of the trial retaining the term “platinum-refractory/resistant".

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Clinical trials

Clinical Trial Results:
Phase IB-II, open label, multicentre feasibility study of pazopanib in combination with Paclitaxel and Carboplatin in patients with platinumrefractory/ resistant ovarian, fallopian tube or peritoneal carcinoma.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: PFS at year 1

Primary: PFS at year 1

Secondary: Best overall response

Secondary: Best overall response

Secondary: Disease Control Rate

Secondary: Disease Control Rate

Secondary: Progression free survival

Secondary: Progression free survival

Secondary: Overall survival

Secondary: Overall survival

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical trials

Clinical Trial Results: Phase IB-II, open label, multicentre feasibility study of pazopanib in combination with Paclitaxel and Carboplatin in patients with platinumrefractory/ resistant ovarian, fallopian tube or peritoneal carcinoma.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: PFS at year 1

Primary: PFS at year 1

Secondary: Best overall response

Secondary: Best overall response

Secondary: Disease Control Rate

Secondary: Disease Control Rate

Secondary: Progression free survival

Secondary: Progression free survival

Secondary: Overall survival

Secondary: Overall survival

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Phase IB-II, open label, multicentre feasibility study of pazopanib in combination with Paclitaxel and Carboplatin in patients with platinumrefractory/ resistant ovarian, fallopian tube or peritoneal carcinoma.