Symptoms and General Pathology

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Carcinoma, Ovarian Epithelial

Ascites

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Genital Diseases

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Female Urogenital Diseases and Pregnancy Complications

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Ovarian Cancer

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Angiogenesis Inhibitors

Aflibercept

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Growth Inhibitors

Participants with advanced ovarian cancer administered placebo in the double-blind (DB) period.

In the open-label (OL) period, participants had the option to receive aflibercept or be withdrawn from the study.

Participants with advanced ovarian cancer administered aflibercept in the double-blind (DB) period.

In the open-label (OL) period, participants had the option to continue to receive aflibercept or be withdrawn from the study.

4.0 mg/kg aflibercept was administered intravenously (IV) over 1 hour once every 2 weeks in the DB period.

aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)

Placebo was administered intravenously (IV) over 1 hour once every 2 weeks in the DB period.

Placebo

4.0 mg/kg aflibercept was administered intravenously (IV) over 1 hour once every 2 weeks in the OL period.

Walter GOTLIEB

This study was designed to characterize the effect of aflibercept in participants with advanced chemoresistant ovarian cancer.

Primary objective: Compare the effect of aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) to placebo treatment on repeat paracentesis in symptomatic malignant ascites in participants with advanced ovarian cancer

Secondary objectives: Safety, tolerability, paracentesis-related parameters, participant-reported outcome.

The study included:

* A Thirty (30)-day screening phase
* The double blind treatment period for a minimum of 60 days. Day 1 of the double-blind treatment period was defined as the date of the qualifying paracentesis (ie, withdrawal of \>= 1 Liter of ascitic fluid). Participants were randomized after adequate recovery from the qualifying paracentesis (The first dose was administered on Day 1 or Day 2).
* The optional open-label extension (until treatment discontinuation criteria were met)
* A posttreatment follow-up phase lasting 60 days.

Criteria for discontinuation included:

1. Participant or his legally authorized representative request discontinuation
2. In the Investigator's opinion, continuation of treatment would be detrimental to the participant's well being, such as disease progression, unacceptable toxicity, noncompliance, or logistical considerations
3. Sponsor request
4. Intercurrent illness that prevented further administration of investigational product(IP)
5. More than 2 IP dose reductions
6. Unacceptable adverse events (AE) not manageable by symptomatic therapy, dose delay, or dose modification
7. Arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset or worsening of preexisting angina
8. Radiographic evidence of intestinal obstruction (for example, dilated loops of bowel accompanied by air-fluid levels) or gastrointestinal perforation (for example, presence of extraluminal gas) requiring surgical intervention

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

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-arm Study of the Effect of Intravenous Aflibercept Administered Every 2 Weeks in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites

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.

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 (-).

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.

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.

Regeneron Pharmaceuticals

Sanofi

Adverse events were collected and reported per arm only as there was no washout period between the double-blind and open label treatment periods.

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.

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

< 35 years

>=35 to <45 years

>=45 to <55 years

>=55 to <65 years

>=65 to <75 years

>=75 years

Baseline characteristics are reported for the randomized population

Age, Customized

Sex: Female, Male

Caucasian

Black

Asian, Oriental

Race/Ethnicity, Customized

Trial Transparency Team

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

Time to Repeat Paracentesis (TRP)

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

Area Under the Curve (AUC) for Participant Assessed Ascites Impact Measure (AIM)

60-Day Frequency of Paracentesis (FOP)

Peak Free Aflibercept (C1) (N=20, N=15)

Trough Free Aflibercept (Beyond C3) (N=15, N=19)

Trough Bound Aflibercept (Beyond C3) (N=16, N=17)

Participants with advanced ovarian cancer administered placebo or 4.0 mg/kg aflibercept intravenously, once every two weeks in the DB period.

Double Blind (DB) Period

Participants with advanced ovarian cancer administered 4.0 mg/kg aflibercept intravenously, once every two weeks in the OL period.

Open-Label (OL) Period

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of the Effect of Intravenous AVE0005 (VEGF Trap) in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites	NCT00327444	Ovarian Neoplas... Ascites	aflibercept (zi... Placebo aflibercept (zi...	18 Years -	Sanofi
Study of the Effect of Intravenous AVE0005 (VEGF Trap) in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites	NCT00327444	Ovarian Neoplas... Ascites	aflibercept (zi... Placebo aflibercept (zi...	18 Years -	Sanofi

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