Trial Outcomes & Findings for Study of the Effect of Intravenous AVE0005 (VEGF Trap) in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites (NCT NCT00327444)

Last Updated: 2013-01-01

Results Overview

TRP was defined as the number of days between the date of randomization and the date of the first post-randomization paracentesis. For participants who did not undergo a postrandomization paracentesis on study, TRP was calculated from randomization to the end of the double-blind treatment period.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

58 participants

Primary outcome timeframe

From Day 1 up to 6 months from randomization

Results posted on

2013-01-01

Participant Flow

Fifty-eight (58) participants from a total of 23 sites in 7 countries were enrolled in the study.

55 were randomized (started population). 3 participants were not randomized but they were treated, and permanently withdrawn from the study due to disease progression (1 participant), fatal disease progression (1 participant) and a treatment emergent adverse event (1 participant).

Participant milestones

Participant milestones
Measure	Placebo Participants with advanced ovarian cancer administered placebo intravenously, once every two weeks in the DB period and 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period.	Aflibercept Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period and the OL period.
Double Blind Treatment (DB) Period STARTED	26	29
Double Blind Treatment (DB) Period SAFETY	25	30
Double Blind Treatment (DB) Period COMPLETED	0	0
Double Blind Treatment (DB) Period NOT COMPLETED	26	29
Open Label Treatment (OL) Period STARTED	11	10
Open Label Treatment (OL) Period ONGOING TREATMENT	1	0
Open Label Treatment (OL) Period COMPLETED	0	0
Open Label Treatment (OL) Period NOT COMPLETED	11	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants with advanced ovarian cancer administered placebo intravenously, once every two weeks in the DB period and 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period.	Aflibercept Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period and the OL period.
Double Blind Treatment (DB) Period Disease progression	10	13
Double Blind Treatment (DB) Period Adverse Event	5	5
Double Blind Treatment (DB) Period Subject request	0	1
Double Blind Treatment (DB) Period Withdrew DB and continued to OL	11	10
Open Label Treatment (OL) Period Disease progression	8	7
Open Label Treatment (OL) Period Adverse Event	2	2
Open Label Treatment (OL) Period Worsening dyspnea	0	1
Open Label Treatment (OL) Period Ongoing Treatment	1	0

Baseline Characteristics

Study of the Effect of Intravenous AVE0005 (VEGF Trap) in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=26 Participants Participants with advanced ovarian cancer administered placebo intravenously, once every two weeks in the DB period and 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period.	Aflibercept n=29 Participants Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period and the OL period.	Total n=55 Participants Total of all reporting groups
Age, Customized < 35 years	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants
Age, Customized >=35 to <45 years	5 participants n=93 Participants	1 participants n=4 Participants	6 participants n=27 Participants
Age, Customized >=45 to <55 years	10 participants n=93 Participants	7 participants n=4 Participants	17 participants n=27 Participants
Age, Customized >=55 to <65 years	4 participants n=93 Participants	11 participants n=4 Participants	15 participants n=27 Participants
Age, Customized >=65 to <75 years	6 participants n=93 Participants	7 participants n=4 Participants	13 participants n=27 Participants
Age, Customized >=75 years	1 participants n=93 Participants	2 participants n=4 Participants	3 participants n=27 Participants
Sex: Female, Male Female	26 Participants n=93 Participants	29 Participants n=4 Participants	55 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race/Ethnicity, Customized Caucasian	19 participants n=93 Participants	22 participants n=4 Participants	41 participants n=27 Participants
Race/Ethnicity, Customized Black	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Race/Ethnicity, Customized Asian, Oriental	6 participants n=93 Participants	7 participants n=4 Participants	13 participants n=27 Participants

PRIMARY outcome

Timeframe: From Day 1 up to 6 months from randomization

Population: The intent-to-treat (ITT) population - all participants who were randomized in the study.

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Participants with advanced ovarian cancer administered placebo intravenously, once every two weeks in the DB period and 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period.	Aflibercept n=29 Participants Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period and the OL period.
Time to Repeat Paracentesis (TRP)	23.3 days Standard Error 7.70	55.1 days Standard Error 7.25

SECONDARY outcome

Timeframe: From Day 1 up to 60 days from randomization to the first postrandomization paracentesis

Population: The intent-to-treat (ITT) population - all participants who were randomized in the study, and had evaluable AIM scores.

AIM 4 symptoms (abdominal discomfort, abdominal bloating, abdominal pain, and ability to move normally) are scored from 0 to 5, where higher scores represent worst outcomes. An AIM total score ranges from 0-20. A plot for (The AIM questionnaire total score - Baseline score) versus time were generated. AIM AUC represents the overall improvement (scored positive) if the area is below the baseline value or worsening (scored negative) if the area is above the baseline. AIM AUC for a participant is the sum of individual areas representing improvement (+) or worsening (-).

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Participants with advanced ovarian cancer administered placebo intravenously, once every two weeks in the DB period and 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period.	Aflibercept n=16 Participants Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period and the OL period.
Area Under the Curve (AUC) for Participant Assessed Ascites Impact Measure (AIM)	29.8 (units on a 4-symptom scale)*day Standard Error 148.07	405.3 (units on a 4-symptom scale)*day Standard Error 143.21

SECONDARY outcome

Timeframe: From Day 1 up to 60 days from randomization

Population: The intent-to-treat (ITT) population - all participants who were randomized in the study.

60-Day FOP was defined as the total number of paracenteses performed within the first 60 days after randomization during the double blind treatment period.

Outcome measures

Outcome measures
Measure	Placebo n=26 Participants Participants with advanced ovarian cancer administered placebo intravenously, once every two weeks in the DB period and 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period.	Aflibercept n=29 Participants Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period and the OL period.
60-Day Frequency of Paracentesis (FOP)	5.1 paracentesis Standard Error 0.69	2.7 paracentesis Standard Error 0.65

SECONDARY outcome

Timeframe: Following every biweekly treatment administration up to 60 days after treatment discontinuation

Population: The analysis was performed using the safety population with evaluable blood samples. 42 participants were evaluated.

Free aflibercept and VEGF-bound aflibercept plasma concentrations were measured by separate enzyme-linked immunosorbent assay (ELISA). The limit of quantitation of free aflibercept was 15.6 ng/mL, and of VEGF-bound aflibercept was 43.9 ng/mL. Peak free aflibercept was estimated at the end of Cycle 1 (C1) administration. The median free and VEGF-bound trough concentrations were determined for each participant beyond Cycle 3 (C3), then mean values were estimated from these median values.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Participants with advanced ovarian cancer administered placebo intravenously, once every two weeks in the DB period and 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period.	Aflibercept n=21 Participants Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period and the OL period.
Plasma Levels of Free and VEGF-bound Aflibercept Peak Free Aflibercept (C1) (N=20, N=15)	69.8 μg/mL Standard Deviation 29.7	62.1 μg/mL Standard Deviation 29.5
Plasma Levels of Free and VEGF-bound Aflibercept Trough Free Aflibercept (Beyond C3) (N=15, N=19)	5.33 μg/mL Standard Deviation 3.67	5.10 μg/mL Standard Deviation 5.29
Plasma Levels of Free and VEGF-bound Aflibercept Trough Bound Aflibercept (Beyond C3) (N=16, N=17)	3.02 μg/mL Standard Deviation 1.29	3.49 μg/mL Standard Deviation 1.48

Adverse Events

Placebo

Serious events: 18 serious events

Other events: 22 other events

Deaths: 0 deaths

Aflibercept

Serious events: 27 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator shall have the right to independently publish study results from his site after a multicenter publication, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication derived from the study for review and comment at least 45 days (20 days) in advance of any submission, and delay publication till the approval of the publication is given in writing by the Sponsor (not to exceed ninety days).
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Placebo n=25 participants at risk Participants with advanced ovarian cancer administered placebo intravenously, once every two weeks in the DB period and 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period.	Aflibercept n=30 participants at risk Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period and the OL period.
Blood and lymphatic system disorders Anaemia	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Blood and lymphatic system disorders Febrile neutropenia	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Blood and lymphatic system disorders Pancytopenia	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Cardiac disorders Cardiopulmonary failure	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Cardiac disorders Pericardial effusion	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Abdominal pain	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	10.0% 3/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Ascites	8.0% 2/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Colonic fistula	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Diarrhoea	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Gastric ulcer haemorrhage	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Intestinal obstruction	8.0% 2/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Intestinal perforation	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Large intestine perforation	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Nausea	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Obstruction gastric	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Small intestinal obstruction	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	10.0% 3/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Small intestinal perforation	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Vomiting	12.0% 3/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	20.0% 6/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Asthenia	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Death	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Disease progression	32.0% 8/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	33.3% 10/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Fatigue	8.0% 2/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Multi-organ failure	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Oedema peripheral	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Pain	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Pyrexia	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Infections and infestations Abscess	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Infections and infestations Fungal skin infection	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Infections and infestations Pneumonia	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Infections and infestations Sepsis	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Infections and infestations Upper respiratory tract infection	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Injury, poisoning and procedural complications Hip fracture	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Investigations Blood electrolytes abnormal	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Metabolism and nutrition disorders Anorexia	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Metabolism and nutrition disorders Dehydration	16.0% 4/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	13.3% 4/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Metabolism and nutrition disorders Hypoglycaemia	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Nervous system disorders Headache	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.

Other adverse events
Measure	Placebo n=25 participants at risk Participants with advanced ovarian cancer administered placebo intravenously, once every two weeks in the DB period and 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period.	Aflibercept n=30 participants at risk Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period and the OL period.
Blood and lymphatic system disorders Anaemia	16.0% 4/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	10.0% 3/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Cardiac disorders Tachycardia	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Abdominal distension	8.0% 2/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	16.7% 5/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Abdominal pain	20.0% 5/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	16.7% 5/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Abdominal pain upper	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	20.0% 6/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Constipation	12.0% 3/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	16.7% 5/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Diarrhoea	20.0% 5/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	40.0% 12/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Dyspepsia	8.0% 2/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	16.7% 5/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Nausea	36.0% 9/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	36.7% 11/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Oral pain	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Stomatitis	8.0% 2/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Gastrointestinal disorders Vomiting	52.0% 13/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	63.3% 19/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Asthenia	12.0% 3/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	23.3% 7/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Chest pain	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Fatigue	56.0% 14/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	33.3% 10/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Gait disturbance	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Mucosal inflammation	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Oedema peripheral	40.0% 10/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	36.7% 11/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
General disorders Pyrexia	8.0% 2/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	10.0% 3/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Infections and infestations Nasopharyngitis	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Infections and infestations Pneumonia	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	10.0% 3/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Infections and infestations Upper respiratory tract infection	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Infections and infestations Urinary tract infection	16.0% 4/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	3.3% 1/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Investigations Weight decreased	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	16.7% 5/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Metabolism and nutrition disorders Anorexia	36.0% 9/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	26.7% 8/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Metabolism and nutrition disorders Dehydration	8.0% 2/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	13.3% 4/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Metabolism and nutrition disorders Hypoalbuminaemia	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	10.0% 3/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Metabolism and nutrition disorders Hyponatraemia	8.0% 2/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Musculoskeletal and connective tissue disorders Arthralgia	12.0% 3/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	0.00% 0/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Musculoskeletal and connective tissue disorders Back pain	16.0% 4/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	23.3% 7/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Musculoskeletal and connective tissue disorders Muscle spasms	8.0% 2/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	10.0% 3/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Musculoskeletal and connective tissue disorders Muscular weakness	8.0% 2/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	10.0% 3/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Musculoskeletal and connective tissue disorders Myalgia	12.0% 3/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Musculoskeletal and connective tissue disorders Pain in extremity	8.0% 2/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Nervous system disorders Dizziness	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Nervous system disorders Dysgeusia	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Nervous system disorders Headache	4.0% 1/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	23.3% 7/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.
Psychiatric disorders Confusional state	0.00% 0/25 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.	6.7% 2/30 • From treatment initiation to October 30, 2009 Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.