Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00396591
Recruitment Status : Completed
First Posted : November 7, 2006
Results First Posted : January 10, 2013
Last Update Posted : January 10, 2013
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Ovarian Neoplasms
Intervention Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Enrollment 16
Recruitment Details 17 participants were screened for this study, of which 16 participants were enrolled.
Pre-assignment Details  
Arm/Group Title Aflibercept
Hide Arm/Group Description Participants with advanced ovarian epithelial cancer treated with 4.0 mg/kg Aflibercept every 2 weeks until a criterion for treatment discontinuation was met
Period Title: Overall Study
Started 16
Completed 0
Not Completed 16
Reason Not Completed
Disease Progression             13
Adverse Event             2
Participant request             1
Arm/Group Title Aflibercept
Hide Arm/Group Description Participants with advanced ovarian epithelial cancer treated with 4.0 mg/kg Aflibercept every 2 weeks until a criterion for treatment discontinuation was met
Overall Number of Baseline Participants 16
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants
59.3  (8.9)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants
<65 years 11
>=65 years 5
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Female
16
 100.0%
Male
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Caucasian Number Analyzed 16 participants
16
Primary tumor site - Ovaries  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants
16
Time since initial cancer diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants
2.8  (1.7)
Histology  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants
Serous 9
Endometrioid 3
Clear cell (mesonephroid) 1
Other 1
Missing data 2
Histology grade  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants
Unknown 5
Moderately differentiated 1
Poorly differentiated 10
Prior anticancer surgeries,  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants
No 1
Yes 15
Baseline interval of paracentesis   [1] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 16 participants
16.5  (7.8)
[1]
Measure Description: Average of the two paracentesis intervals prior to the Day 1 paracentesis before registration.
Eastern Cooperative Oncology Group (ECOG) performance status score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 16 participants
ECOG Score = 0 3
ECOG Score = 1 10
ECOG Score = 2 3
[1]
Measure Description: The ECOG score assesses how the disease affects a participant's daily living abilities. It ranges from 0-5, with 0 being the best and 5 being the worst outcome. "0" reflects a fully active participant, able to carry on all pre-disease performance without restriction. "1" reflects a participant restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. "2" reflects an ambulatory participant, who is up and about more than 50% of waking hours, and capable of all self-care but unable to carry out any work activities.
1.Primary Outcome
Title Percentage of Participants With a Repeat Paracentesis Response (RPR)
Hide Description

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.

Time Frame up to 2 years post-registration
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aflibercept
Hide Arm/Group Description:
Participants with advanced ovarian epithelial cancer treated with 4.0 mg/kg Aflibercept every 2 weeks until a criterion for treatment discontinuation was met
Overall Number of Participants Analyzed 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
62.5
(35.43 to 84.80)
2.Secondary Outcome
Title Time to Repeat Paracentesis (TRP)
Hide Description 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.
Time Frame up to 6 months from registration
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were analyzed. 8 had one or more paracentesis events. Participants with no paracentesis events were censored at the end of the treatment period (last dose + 1 cycle).
Arm/Group Title Aflibercept
Hide Arm/Group Description:
Participants with advanced ovarian epithelial cancer treated with 4.0 mg/kg Aflibercept every 2 weeks until a criterion for treatment discontinuation was met
Overall Number of Participants Analyzed 16
Overall Number of Units Analyzed
Type of Units Analyzed: Paracentesis (>/= 1 per participant)
8
Median (95% Confidence Interval)
Unit of Measure: days
76.0
(64.0 to 178.0)
3.Secondary Outcome
Title 60-day Frequency of Paracentesis (FOP)
Hide Description 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.
Time Frame up to 60 days post-registration
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Aflibercept
Hide Arm/Group Description:
Participants with advanced ovarian epithelial cancer treated with 4.0 mg/kg Aflibercept every 2 weeks until a criterion for treatment discontinuation was met
Overall Number of Participants Analyzed 16
Mean (Standard Deviation)
Unit of Measure: paracenteses
1.5  (1.6)
4.Secondary Outcome
Title Progression-free Survival (PFS) Time
Hide Description

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.

Time Frame up to 6 months post-registration
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with a PFS event (tumor progression or death) were analyzed.
Arm/Group Title Aflibercept
Hide Arm/Group Description:
Participants with advanced ovarian epithelial cancer treated with 4.0 mg/kg Aflibercept every 2 weeks until a criterion for treatment discontinuation was met
Overall Number of Participants Analyzed 12
Median (95% Confidence Interval)
Unit of Measure: days
59.5
(41.0 to 83.0)
5.Secondary Outcome
Title Overall Survival (OS) Time
Hide Description 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.
Time Frame up to 6 months post-registration
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were analyzed. 5 participants who died after efficacy data cutoff date (6 months postregistration) were censored at the data cutoff date.
Arm/Group Title Aflibercept
Hide Arm/Group Description:
Participants with advanced ovarian epithelial cancer treated with 4.0 mg/kg Aflibercept every 2 weeks until a criterion for treatment discontinuation was met
Overall Number of Participants Analyzed 16
Overall Number of Units Analyzed
Type of Units Analyzed: Events (Death)
11
Median (95% Confidence Interval)
Unit of Measure: days
92.0 [1] 
(58.0 to NA)
[1]
Not calculable as some participants were still alive at the cut-off date.
6.Secondary Outcome
Title Number of Participants With a Positive Anti-drug Antibody Response
Hide Description

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.

Time Frame up to 60 days after the last dose of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least part of 1 dose of aflibercept and had evaluable blood samples
Arm/Group Title Aflibercept
Hide Arm/Group Description:
Participants with advanced ovarian epithelial cancer treated with 4.0 mg/kg Aflibercept every 2 weeks until a criterion for treatment discontinuation was met
Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: participants
0
7.Secondary Outcome
Title Safety - Number of Participants With Adverse Events (AE)
Hide Description 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.
Time Frame up to 60 days after last dose of treatment (approximately 2 years), or until TEAE was resolved or stabilized
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least part of 1 dose of the study treatment.
Arm/Group Title Aflibercept
Hide Arm/Group Description:
Participants with advanced ovarian epithelial cancer treated with 4.0 mg/kg Aflibercept every 2 weeks until a criterion for treatment discontinuation was met
Overall Number of Participants Analyzed 16
Measure Type: Number
Unit of Measure: participants
With at least one TEAE 16
With at least one serious TEAE 15
With a TEAE leading to death 8
With a TEAE resulting in discontinuation 2
Time Frame From treatment initiation to January 30, 2009
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Aflibercept
Hide Arm/Group Description Participants with advanced ovarian epithelial cancer treated with 4.0 mg/kg Aflibercept every 2 weeks until a criterion for treatment discontinuation was met
All-Cause Mortality
Aflibercept
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Aflibercept
Affected / at Risk (%)
Total   15/16 (93.75%) 
Blood and lymphatic system disorders   
Anaemia * 1  1/16 (6.25%) 
Cardiac disorders   
Tachyarrhythmia * 1  1/16 (6.25%) 
Gastrointestinal disorders   
Abdominal pain * 1  1/16 (6.25%) 
Intestinal obstruction * 1  5/16 (31.25%) 
Intestinal perforation * 1  1/16 (6.25%) 
Large intestinal obstruction * 1  1/16 (6.25%) 
Nausea * 1  2/16 (12.50%) 
Small intestinal obstruction * 1  1/16 (6.25%) 
Vomiting * 1  4/16 (25.00%) 
General disorders   
Disease progression * 1  4/16 (25.00%) 
General physical health deterioration * 1  1/16 (6.25%) 
Infections and infestations   
Gastroenteritis * 1  1/16 (6.25%) 
Metabolism and nutrition disorders   
Dehydration * 1  1/16 (6.25%) 
Nervous system disorders   
Cognitive disorder * 1  1/16 (6.25%) 
Respiratory, thoracic and mediastinal disorders   
Hydropneumothorax * 1  1/16 (6.25%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Aflibercept
Affected / at Risk (%)
Total   16/16 (100.00%) 
Blood and lymphatic system disorders   
Anaemia * 1  1/16 (6.25%) 
Lymphadenitis * 1  1/16 (6.25%) 
Cardiac disorders   
Tachyarrhythmia * 1  1/16 (6.25%) 
Eye disorders   
Conjunctivitis * 1  1/16 (6.25%) 
Gastrointestinal disorders   
Abdominal distension * 1  2/16 (12.50%) 
Abdominal pain * 1  6/16 (37.50%) 
Abdominal pain upper * 1  2/16 (12.50%) 
Colitis * 1  1/16 (6.25%) 
Constipation * 1  3/16 (18.75%) 
Diarrhoea * 1  2/16 (12.50%) 
Dyspepsia * 1  1/16 (6.25%) 
Gastritis * 1  1/16 (6.25%) 
Gastrooesophageal reflux disease * 1  1/16 (6.25%) 
Intestinal obstruction * 1  1/16 (6.25%) 
Intestinal perforation * 1  1/16 (6.25%) 
Nausea * 1  6/16 (37.50%) 
Oesophagitis * 1  1/16 (6.25%) 
Subileus * 1  1/16 (6.25%) 
Toothache * 1  1/16 (6.25%) 
Vomiting * 1  8/16 (50.00%) 
General disorders   
Asthenia * 1  5/16 (31.25%) 
Disease progression * 1  5/16 (31.25%) 
Early satiety * 1  2/16 (12.50%) 
Fatigue * 1  4/16 (25.00%) 
General physical health deterioration * 1  1/16 (6.25%) 
Mucosal inflammation * 1  1/16 (6.25%) 
Oedema peripheral * 1  3/16 (18.75%) 
Pain * 1  2/16 (12.50%) 
Pyrexia * 1  1/16 (6.25%) 
Hepatobiliary disorders   
Hepatic failure * 1  1/16 (6.25%) 
Infections and infestations   
Gastroenteritis * 1  2/16 (12.50%) 
Nasopharyngitis * 1  1/16 (6.25%) 
Rhinitis * 1  1/16 (6.25%) 
Tooth infection * 1  1/16 (6.25%) 
Urinary tract infection * 1  1/16 (6.25%) 
Investigations   
Cardiac murmur * 1  1/16 (6.25%) 
Urine output decreased * 1  1/16 (6.25%) 
Urine output increased * 1  1/16 (6.25%) 
Weight decreased * 1  2/16 (12.50%) 
Metabolism and nutrition disorders   
Anorexia * 1  5/16 (31.25%) 
Decreased appetite * 1  1/16 (6.25%) 
Dehydration * 1  2/16 (12.50%) 
Hypokalaemia * 1  1/16 (6.25%) 
Hyponatraemia * 1  2/16 (12.50%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  2/16 (12.50%) 
Back pain * 1  3/16 (18.75%) 
Musculoskeletal pain * 1  1/16 (6.25%) 
Neck pain * 1  1/16 (6.25%) 
Nervous system disorders   
Dizziness * 1  1/16 (6.25%) 
Dysgeusia * 1  1/16 (6.25%) 
Headache * 1  3/16 (18.75%) 
Neuropathy peripheral * 1  1/16 (6.25%) 
Peripheral sensory neuropathy * 1  1/16 (6.25%) 
Psychiatric disorders   
Insomnia * 1  2/16 (12.50%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  1/16 (6.25%) 
Dysphonia * 1  3/16 (18.75%) 
Pleural effusion * 1  1/16 (6.25%) 
Sinus congestion * 1  1/16 (6.25%) 
Skin and subcutaneous tissue disorders   
Alopecia * 1  1/16 (6.25%) 
Hyperhidrosis * 1  1/16 (6.25%) 
Palmar-plantar erythrodysaesthesia syndrome * 1  1/16 (6.25%) 
Rash * 1  2/16 (12.50%) 
Skin exfoliation * 1  1/16 (6.25%) 
Vascular disorders   
Hypertension * 1  7/16 (43.75%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The investigator has the right to independently publish study results from his site after a multicenter publication, or 12 months after the completion of the study by all sites. He must provide the sponsor a copy of any such publication derived from the study for review and comment at least 45 days (20 for abstracts) in advance of any submission for publication. The Sponsor may request for the publication to be delayed for a limited time, not to exceed 90 days to preserve its proprietary rights.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: sanofi-aventis
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00396591     History of Changes
Other Study ID Numbers: ARD6772
EUDRACT: 2006-000604-16
First Submitted: November 6, 2006
First Posted: November 7, 2006
Results First Submitted: August 17, 2012
Results First Posted: January 10, 2013
Last Update Posted: January 10, 2013