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

Sanofi

Status and phase: Completed; Phase 3; Phase 2

Conditions: Ovarian Neoplasms; Ascites

Treatments: Drug: aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00327444

AVE0005A /3001

EFC6125

EudraCT : 2005-005026-31

Details and patient eligibility

About

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.

Full description

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

Enrollment: 58 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Participants who met the following criteria were eligible to participate in this study.

Inclusion Criteria:

• Advanced ovarian epithelial cancer, treated with paracentesis
• Platinum-resistant, and topotecan-resistant and/or liposomal doxorubicin-resistant disease;
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2.

Exclusion Criteria:

• Pseudomyxoma peritonei or peritoneal mesothelioma;
• Transudative ascites;
• Peritoneovenous or other shunt placed for malignant ascites management;
• Recent (<6 months) cardiovascular event (pulmonary embolus, myocardial infarction, stroke) or gastrointestinal disease (ulcer, hepatic cirrhosis);
• Known brain metastases;
• Uncontrolled hypertension;
• Recent treatment with chemotherapy, surgery or radiotherapy;
• Prior treatment with VEGF or VEGFR inhibitor.

The above information is not intended to contain all considerations relevant to participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

58 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

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

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

Drug: Placebo

Aflibercept

Experimental group

Description:

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.

Treatment:

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

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