Study of AVE0005 (VEGF Trap) in Patients With Chemoresistant Advanced Ovarian Cancer

NCT ID: NCT00327171

Last Updated: 2016-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 218 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2010-03-31

Brief Summary

This study evaluated outcomes in participants with advanced ovarian epithelial adenocarcinoma receiving aflibercept.

The primary objective was to compare the objective response rate of Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) 4.0 mg/kg and 2.0 mg/kg, administered intravenously (IV) every 2 weeks with historical control in participants with advanced ovarian epithelial (including fallopian tube and primary peritoneal) adenocarcinoma resistant to platinum and topotecan and/or liposomal doxorubicin.

The secondary objectives was to further assess efficacy, safety, pharmacokinetics, potential biological and pharmacogenomic markers of study drug activity, and health-related quality of life.

This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation. If an endpoint was evaluated by the IRC, the IRC reviewed data is reported for this study.

Detailed Description

The study included:

• A screening period for 21 days
• Randomization at baseline (Treatment was initiated with 5 days of randomization)
• A treatment period with 14-day study treatment cycles until a study withdrawal criterion was met
• A follow-up period up to 60 days after the end of treatment

Withdrawal criteria that led to treatment discontinuation were:

• The participant or their legally authorized representative requested to withdraw
• In the investigator's opinion, continuation of the study would be detrimental to the participant's well being, due to reasons such as disease progression, unacceptable toxicity, noncompliance, or logistical considerations.
• A specific request by the Sponsor
• Participant had intercurrent illness that prevented further administration of study treatment
• Participant had more than 2 aflibercept dose reductions
• Participant had arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset or worsening of pre-existing angina
• Participant had radiographic evidence of intestinal obstruction (e.g., dilated loops of bowel accompanied by air-fluid levels) or gastrointestinal perforation (e.g., presence of extraluminal gas) requiring surgical intervention
• Participant was lost to follow-up

After discontinuing treatment, participants remained on the study until the last post-treatment visit or until recovery of drug related toxicities, whichever was later.

Conditions

Neoplasms; Cancer of the Ovary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Aflibercept 2.0 mg/kg

Participants with advanced ovarian epithelial adenocarcinoma administered 2.0 mg/kg Aflibercept.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

Aflibercept 2.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.

Aflibercept could be reduced by 1 dose level (to 1.0 mg/kg) or 2 dose levels (to 0.5 mg/kg) in case of uncontrolled hypertension or urinary protein >3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.

Aflibercept 4.0 mg/kg

Participants with advanced ovarian epithelial adenocarcinoma administered 4.0 mg/kg Aflibercept.

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

Aflibercept 4.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.

Aflibercept could be reduced by 1 dose level ( to 2.0 mg/kg) or 2 dose levels (to 1.0 mg/kg) in case of uncontrolled hypertension or urinary protein >3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.

Interventions

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

Aflibercept 4.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.

Aflibercept could be reduced by 1 dose level ( to 2.0 mg/kg) or 2 dose levels (to 1.0 mg/kg) in case of uncontrolled hypertension or urinary protein >3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.

Intervention Type: DRUG

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

Aflibercept 2.0 mg/kg administered intravenously (IV) over 1 hour once every 2 weeks.

Aflibercept could be reduced by 1 dose level (to 1.0 mg/kg) or 2 dose levels (to 0.5 mg/kg) in case of uncontrolled hypertension or urinary protein >3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically-confirmed ovarian epithelial (including fallopian tube and primary peritoneal) adenocarcinoma.
• Prior treatment with at least 2 treatment regimens in the advanced disease treatment setting
• Platinum-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance
• Topotecan- and/or liposomal doxorubicin-resistant disease defined by relapse or progression of disease during or after treatment, or drug intolerance
• Evidence of at least one unidimensional measurable tumor lesion by computed tomography (CT) or magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria in Solid Tumors (RECIST) that has not been treated with surgery or radiation therapy

Exclusion Criteria

• Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the cervix uteri
• Prior treatment with a vascular endothelial growth factor (VEGF) or VEGF receptor inhibitor
• More than 3 chemotherapy regimens in the advanced disease treatment setting
• Uncontrolled hypertension

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ICD CSD

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States

Sanofi-Aventis Administrative Office

Macquarie Park, , Australia

Sanofi-Aventis Administrative Office

Laval, , Canada

Sanofi-Aventis Administrative Office

Paris, , France

Sanofi-Aventis Administrative Office

Berlin, , Germany

Sanofi-Aventis Administrative Office

Milan, , Italy

Sanofi-Aventis Administrative Office

Gouda, , Netherlands

Sanofi-Aventis Administrative Office

Porto Salvo, , Portugal

Sanofi-Aventis Administrative Office

Barcelona, , Spain

Sanofi-Aventis Administrative Office

Bromma, , Sweden

Sanofi-Aventis Administrative Office

Geneva, , Switzerland

Countries

United States; Australia; Canada; France; Germany; Italy; Netherlands; Portugal; Spain; Sweden; Switzerland

References

Tew WP, Colombo N, Ray-Coquard I, Del Campo JM, Oza A, Pereira D, Mammoliti S, Matei D, Scambia G, Tonkin K, Shun Z, Sternas L, Spriggs DR. Intravenous aflibercept in patients with platinum-resistant, advanced ovarian cancer: results of a randomized, double-blind, phase 2, parallel-arm study. Cancer. 2014 Feb 1;120(3):335-43. doi: 10.1002/cncr.28406. Epub 2013 Oct 11.

Reference Type: RESULT

PMID: 24127346 (View on PubMed)

Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

Reference Type: DERIVED

PMID: 37185961 (View on PubMed)

Other Identifiers

AVE0005

Identifier Type: -

Identifier Source: secondary_id

ARD6122

Identifier Type: -

Identifier Source: org_study_id