AVE0005 (VEGF Trap) in Patients With Recurrent Symptomatic Malignant Ascites

Ovarian Neoplasms Clinical Trial

Official title:

A Multicenter, Open-label, Single-arm Study of the Efficacy and Safety of Intravenous AVE0005 (VEGF Trap) Administered Every 2 Weeks in Advanced Ovarian Cancer Patients With Recurrent Symptomatic Malignant Ascites

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00396591
• Other study ID #: ARD6772
• Secondary ID: EUDRACT: 2006-00
• Status: Completed
• Phase: Phase 2
• First received: November 6, 2006
• Last updated: January 9, 2013
• Start date: October 2006
• Est. completion date: November 2008

Study information

• Verified date: July 2011
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationItaly: Ethics CommitteeSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to compare the time between paracenteses before and after administration of Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) in ovarian cancer participants with symptomatic malignant ascites.

The secondary objectives were to further assess efficacy and safety of Aflibercept treatment, and the exploratory objectives were to assess pharmacokinetics, immunogenicity and health-related quality of life.

Description:

The study consisted of:

• A 30-day screening phase prior to Day 1

• Day 1 registration and pre-treatment paracentesis

• Aflibercept administration within 1-day of registration

• Two-week study treatment cycles (for efficacy data, the cut-off date was 6 months post-registration

• A 60-day post-treatment follow-up phase

During the study, participants were treated with Aflibercept study treatment through the duration of the study unless they met one the following criteria for discontinuation:

• Participant (or legal representative) chose to withdraw from treatment

• The investigator or sponsor thought that continuation of the study would be detrimental to the participants well-being

• Participant had intercurrent illness that prevented further administration of investigational product (IP)

• Participant had more than 2 IP dose reductions

• Participant had unacceptable adverse events (AEs)

• Participant had arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset angina, or worsening of preexisting angina

• Participant required surgical intervention for intestinal obstruction or gastrointestinal perforation

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Participants that met the following criteria were eligible.

Inclusion Criteria:

• Symptomatic malignant ascites resulting from advanced ovarian epithelial cancer (including fallopian tube and primary peritoneal adenocarcinoma) that required at least 3 previous therapeutic paracenteses at a frequency of 1 to 4 paracenteses per month for management.

• 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.

Exclusion Criteria:

• Peritoneovenous or other type of shunt that was placed for the management of ascites

• Prior treatment with a VEGF or VEGF receptor inhibitor

• Uncontrolled hypertension

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Neoplasms

Intervention

Drug:
• Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
4.0 mg/kg administered intravenously (IV) once every 2 weeks

Locations

Country	Name	City	State
Italy	Sanofi-Aventis Administrative Office	Milano
Sweden	Sanofi-Aventis Administrative Office	Bromma
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Italy,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a Repeat Paracentesis Response (RPR)	RPR was defined as at least a two-fold increase in the time to repeat paracentesis (TRP) as compared to the average duration of the 2 intervals between the 3 most recent paracenteses prior to study registration (ie, the baseline interval of paracentesis).; Percentage of participants with a repeat paracentesis response were the number of participants with RPR / number of total participants * 100.	up to 2 years post-registration	No
Secondary	Time to Repeat Paracentesis (TRP)	TRP is the number of days between the date of registration and the date of the first postregistration paracentesis. Median TRP was estimated from Kaplan-Meier curves. For participants who did not undergo a postregistration paracentesis while on study, TRP was censored at the end of the treatment period (last dose + 1 cycle), at the last visit known without repeat paracentesis, at 6 months postregistration, or at death, whichever was earlier.	up to 6 months from registration	No
Secondary	60-day Frequency of Paracentesis (FOP)	FOP was the total number of paracenteses performed within the first 60 days postregistration. For participants who had withdrawn after registration but prior to the 60-day cutoff date, the withdrawal would have been regarded as a paracentesis event and the 60-day FOP normalized and calculated as the nearest integer of the value corresponding to 60 × number of paracenteses / x, where x represents the number of days on study.	up to 60 days post-registration	No
Secondary	Progression-free Survival (PFS) Time	According to the Response Evaluation Criteria in Solid Tumors [RECIST], progression was at least a 20% increase in the sum of the longest diameter (LD) of tumors, compared to smallest sum LD recorded since treatment started, or the appearance of one or more new tumors.; PFS time was interval from the date of registration to the date of tumor progression or death from any cause, whichever was earlier. Median PFS time was estimated from Kaplan-Meier Plots.; If participants were alive and progression-free at 6 months postregistration, they were censored for PFS.	up to 6 months post-registration	No
Secondary	Overall Survival (OS) Time	OS time was the time interval between the date of registration to the date of death from any cause. Median OS was estimated from Kaplan-Meier curves. Participants who died after efficacy data cutoff date (6 months postregistration) were censored at the data cutoff date.	up to 6 months post-registration	No
Secondary	Number of Participants With a Positive Anti-drug Antibody Response	Anti-drug antibodies in participant's serum were measured using 2 different methods; an Enzyme Linked Immunosorbent Assay (ELISA) in which the lower limit of detection (LLOD) was 238.4 ng/mL; and; an Electrochemiluminescence-based, Bridging Assay in which the validated LLOD was about 5.4 ng/mL in the absence of aflibercept and about 25.2 ng/mL in the presence of 20 µg/mL of aflibercept.; Participants with detectable anti-drug antibodies by either method were considered to have a positive anti-drug antibody response.	up to 60 days after the last dose of treatment	No
Secondary	Safety - Number of Participants With Adverse Events (AE)	All AEs regardless of seriousness or relationship to study treatment, spanning from the first administration of study treatment until 60 days after the last administration of study treatment, were recorded, and followed until resolution or stabilization. The number of participants with all treatment emergent adverse events (TEAE), serious adverse events (SAE), TEAE leading to death, and TEAE leading to permanent treatment discontinuation are reported.	up to 60 days after last dose of treatment (approximately 2 years), or until TEAE was resolved or stabilized	Yes