Clinical trial NCT00327171: Study of AVE0005 (VEGF Trap) in Patients With Chemoresistant Advanced Ovarian Cancer
Official title: A Multicenter, Randomized, Double-blind, Parallel-arm, Two-stage Study of the Efficacy and Safety of AVE0005 (VEGF Trap) Administered Intravenously Every 2 Weeks in Patients With Platinum-resistant and topotecan-and/or Liposomal Doxorubicin-resistant Advanced Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neoplasms
Cancer of the Ovary
Keywords: ovarian cancer
angiogenesis
angiogenesis inhibition
VEGF-Trap fusion recombinant protein
Cancer and other neoplasms
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2006-05-18
Enrollment: 218
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Participants who met the following criteria were eligible for the study.

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.

Primary outcomes:
measure: Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by an Independent Review Committee (IRC) - Simon's Cohort
timeFrame: From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
measure: Number of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Based on the Analysis by the IRC - Efficacy Evaluable Population
timeFrame: From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
Secondary outcomes:
measure: Number of Participants With a Clinical Benefit Response (CBR) as Per RECIST Based on the Analysis by the IRC
timeFrame: From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
measure: Duration of Response (DR) Based on the Analysis by an Independent Review Committee (IRC)
timeFrame: From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
measure: Tumor Marker Response Rate (TMRR) Based on the Gynecologic Cancer Intergroup (GCIG) Definition
timeFrame: From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
measure: Time to Tumor Progression (TTP) as Per RECIST Based on the Analysis by the IRC
timeFrame: From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
measure: Time to Tumor Marker (CA-125) Progression (TTMP)
timeFrame: From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
measure: Number of Participants With Disease Progression Events for Progression-free Survival (PFS) Analysis by the IRC.
timeFrame: From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
measure: Progression-free Survival (PFS) Time Based on Analysis by the IRC
timeFrame: From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
measure: Overall Survival (OS) Time
timeFrame: From enrollment to efficacy cut-off date, 18 January 2008 (approximately 20 months)
measure: Overall Safety - Number of Participants With Adverse Events (AE)
timeFrame: up to 30+/-5 days after treatment discontinuation, or up to recovery or stabilization of a followed-up adverse event
measure: Participant's Assessment of Health Related Quality of Life (HRQL) Using a by Using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Questionnaire
timeFrame: On Day 1 of Cycle 1 (baseline) , and after Day 14 of Cycle 2
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Macquarie Park
country: Australia
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Paris
country: France
facility: Sanofi-Aventis Administrative Office
city: Berlin
country: Germany
facility: Sanofi-Aventis Administrative Office
city: Milano
country: Italy
facility: Sanofi-Aventis Administrative Office
city: Gouda
country: Netherlands
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Bromma
country: Sweden
facility: Sanofi-Aventis Administrative Office
city: Geneva
country: Switzerland
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: ICD CSD
role: STUDY_DIRECTOR
References:
citation: 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.