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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00519285




Registration number
NCT00519285
Ethics application status
Date submitted
21/08/2007
Date registered
22/08/2007
Date last updated
22/07/2016

Titles & IDs
Public title
Aflibercept in Combination With Docetaxel in Metastatic Androgen Independent Prostate Cancer
Scientific title
A Multicenter, Randomized, Double Blind Study Comparing the Efficacy and Safety of Aflibercept Versus Placebo Administered Every 3 Weeks in Patients Treated With Docetaxel/ Prednisone for Metastatic Androgen-independent Prostate Cancer
Secondary ID [1] 0 0
2006-004756-20
Secondary ID [2] 0 0
EFC6546
Universal Trial Number (UTN)
Trial acronym
VENICE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms 0 0
Neoplasm Metastasis 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Aflibercept
Treatment: Drugs - Placebo (for aflibercept)
Treatment: Drugs - Docetaxel
Treatment: Drugs - Prednisone or Prednisolone

Placebo Comparator: Placebo - Placebo added to standard chemotherapy with docetaxel plus prednisone or prednisolone

Experimental: Aflibercept - Aflibercept added to standard chemotherapy with docetaxel plus prednisone or prednisolone


Treatment: Drugs: Aflibercept
25 mg/ml solution
6 mg/kg, 1-hour IV on Day 1 of each 3-Week cycle

Treatment: Drugs: Placebo (for aflibercept)
Sterile aqueous buffered solution identical to aflibercept
1-hour IV on Day 1 of each 3-Week cycle

Treatment: Drugs: Docetaxel
Marketed formulation
75 mg/m², 1 hour IV on Day 1 of each 3-week cycle (immediately after Aflibercept or placebo)

Treatment: Drugs: Prednisone or Prednisolone
Marketed formulation
5 mg twice daily PO from day 1 continuously

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival Time - Overall survival (OS) time was measured as the time from date of randomization to the date of death due to any cause.
The median OS time and its 95.6% confidence interval were estimated using the Kaplan-Meier method. In the absence of confirmation of death, the participant was censored at the last date he/she was known to be alive or the study cut-off date (when 873 deaths have occurred), whichever was earlier.
Timepoint [1] 0 0
From randomization up to the cut-off date (median follow-up of 35.4 months)
Secondary outcome [1] 0 0
Prostate Specific Antigen Response Rate - Prostate specific antigen (PSA) response was defined as =50% decrease from baseline in serum PSA levels, confirmed at least 3 weeks later. Increases of any magnitude during the first 12 weeks were ignored in determining PSA response.
Timepoint [1] 0 0
Before randomization (baseline) then every 3 weeks up to PSA progression (=25% increase) or the cut-off date, whichever occurred first
Secondary outcome [2] 0 0
Time to Skeletal Related Events - Skeletal Related Events (SRE) included pathological fractures and/or spinal cord compression, need for bone irradiation, including radioisotopes or bone surgery, change in antineoplastic therapy to treat bone pain.
Time to SRE was defined as the time from the date of randomization to the date of occurence of the first event defining a SRE or death due to any cause, whichever occurred first.
The median time to SRE and its 95% confidence interval were estimated using the Kaplan-Meier method. In the absence of SRE, the participant was censored at the last date he/she was known to be alive or the study cut-off date, whichever was earlier.
Timepoint [2] 0 0
From randomization up to the cut-off date (median follow-up of 35.4 months)
Secondary outcome [3] 0 0
Progression Free Survival Time - Disease progression was defined as a composite of: Radiological tumor progression (=20% increase in target lesions, or appearance of at least 2 new bone lesions); PSA progression (=25% increase in PSA level confirmed 3 weeks later); Pain progression (increase in pain intensity or in analgesic consumption for cancer related pain confirmed 3 weeks later); Radiotherapy for cancer related symptoms; Occurence of Skeletal related events (SRE).
Progression Free survival (PFS) time was measured as the time from the date of randomization up to the date of occurrence of the first event defining a disease progression or death due to any cause, whichever occurred first.
The median PFS time and its 95% confidence interval were estimated using the Kaplan-Meier method. In the absence of disease progression, the participant was censored at the the date of last assessment without evidence of progression or the study cut-off date, whichever was earlier.
Timepoint [3] 0 0
From randomization up to the cut-off date (median follow-up of 35.4 months)
Secondary outcome [4] 0 0
Tumor Response Rate in Participants With Measurable Disease - Tumor response was defined as either a Complete Response (disappearance of all target lesions) or a Partial Response (=30% decrease from baseline in target lesions) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST)version 1.0.
Timepoint [4] 0 0
Before randomization (baseline) then every 3 months up to tumor progression (=25% increase) or the cut-off date, whichever occurred first
Secondary outcome [5] 0 0
Prostate Specific Antigen Progression-free Survival Time - Prostate specific antigen (PSA) progression was defined as =25% increase in PSA level confirmed 3 weeks later, above the nadir in participants who had achieved a PSA response, or above the baseline in participants who hadn't achieved a PSA response.
PSA progression-free survival (PFS) time was defined as the time from the date of randomization up to the date of the first documented PSA progression or death due to any cause, whichever occurred first.
The median PSA-PFS time and its 95% confidence interval were estimated using the Kaplan-Meier method. In the absence of PSA progression or death, the participant was censored at the the date of last assessment without evidence of progression or the study cut-off date, whichever was earlier.
Timepoint [5] 0 0
From randomization up to the cut-off date (median follow-up of 35.4 months)
Secondary outcome [6] 0 0
Pain Progression-free Survival Time - Pain progression was defined as either =1-point increase in Present Pain Intensity (PPI) score or =25% increase in Analgesics Score (AS) confirmed at least 3 weeks later, or requirement for palliative radiotherapy. PPI scale is a self-report 0-5 scale to assess pain intensity - a score 0 reflects no pain, a score 5 reflects excruciating pain. AS is a scoring method to assess analgesics consumption. Each analgesic is scored 1 or 4 depending on the analgesic type and dose. AS is the sum of the analgesic scores.
Pain progression-free survival (PFS) time was measured as the time from the date of randomization up to the date of first pain progression or death due to any cause, whichever occurred first.
The median pain-PFS and its 95% confidence interval were estimated using the Kaplan-Meier method. In the absence of event, the participant was censored at the the date of last assessment without evidence of pain progression or the study cut-off date, whichever was earlier.
Timepoint [6] 0 0
From randomization up to the cut-off date (median follow-up of 35.4 months)
Secondary outcome [7] 0 0
Pain Response Rate - Pain response was defined as either a =2-point decrease from baseline in Present Pain Intensity (PPI) score without increase in Analgesics Score (AS), or a =50% decrease from baseline in AS without increase in the PPI score confirmed at least 3 weeks later. Increases in PPI or AS during the first 12 weeks were ignored in determining pain response.
Timepoint [7] 0 0
Before randomization (baseline) then every 3 weeks up to pain progression or the cut-off date, whichever occurred first
Secondary outcome [8] 0 0
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate Total Score as a Measure of Health Related Quality of Life - Functional Assessment of Cancer Therapy-Prostate (FACT-P) is a 39-item participant questionnaire that measures the concerns of patients with prostate cancer. It consists of 5 subscales assessing physical well-being, social/family well-being, emotional well-being, functional well-being, and prostate-specific concerns.
FACT-P total score is the sum of the 5 subscores. It ranges from 0 to 156 with higher score indicating better quality of life.
Timepoint [8] 0 0
Before randomization (baseline) then every 3 weeks until disease progression or administration of further antitumor therapy, whichever came first
Secondary outcome [9] 0 0
Number of Participants With Adverse Events as a Measure of Safety - Adverse Events (AE) are any unfavorable and unintended sign, symptom, syndrome or illness observed by the investigator or reported by the participant during the study.
AE were collected at regular intervals throughout the study then graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v.3.0).
Timepoint [9] 0 0
From first dose of study treatment (aflibercept/placebo or docetaxel whichever came first) to last dose of study treatment (aflibercept/placebo or docetaxel whichever came last) + 30 days
Secondary outcome [10] 0 0
Number of Participants With Positive Anti-aflibercept Antibody Levels as a Measure of Immunogenicity of Aflibercept - Serum for detection of anti-drug antibodies (ADA) was collected in patients treated in selected centers only. Samples were analyzed using a titer-based, bridging immunoassay developed and validated to detect ADAs in human serum.
Samples with positive antibody levels were further analyzed using a validated, non-quantitative ligand binding assay to detect neutralizing antibodies Ab).
A participant was considered to have positive antibody levels if antibodies were detected above the quantification limits.
Timepoint [10] 0 0
Pre-dose of cycle 1 (baseline), pre-dose of each every other cycle, then 30 and 90 days after the last administration of the study drug

Eligibility
Key inclusion criteria
- Histologically- or cytologically-confirmed prostate adenocarcinoma;

- Metastatic disease;

- Progressive disease while receiving hormonal therapy or after surgical castration;

- Effective castration.
Minimum age
18 Years
Maximum age
No limit
Gender
Males
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior cytotoxic chemotherapy for prostate cancer, except estramustine and except
adjuvant/neoadjuvant treatment completed >3 years ago;

- Prior treatment with Vascular Endothelial Growth Factor (VEGF) inhibitors or VEGF
receptor inhibitors;

- Eastern Cooperative Oncology Group (ECOG) performance status >2.

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sanofi-Aventis Administrative Office - Macquarie Park
Recruitment postcode(s) [1] 0 0
- Macquarie Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
Argentina
State/province [2] 0 0
Buenos Aires
Country [3] 0 0
Belgium
State/province [3] 0 0
Diegem
Country [4] 0 0
Brazil
State/province [4] 0 0
Sao Paulo
Country [5] 0 0
Canada
State/province [5] 0 0
Laval
Country [6] 0 0
Chile
State/province [6] 0 0
Providencia Santiago
Country [7] 0 0
Croatia
State/province [7] 0 0
City of Zagreb
Country [8] 0 0
Czech Republic
State/province [8] 0 0
Praha
Country [9] 0 0
Denmark
State/province [9] 0 0
Horsholm
Country [10] 0 0
Estonia
State/province [10] 0 0
Tallinn
Country [11] 0 0
France
State/province [11] 0 0
Paris
Country [12] 0 0
Germany
State/province [12] 0 0
Frankfurt
Country [13] 0 0
Hong Kong
State/province [13] 0 0
Hong Kong
Country [14] 0 0
Hungary
State/province [14] 0 0
Budapest
Country [15] 0 0
Israel
State/province [15] 0 0
Natanya
Country [16] 0 0
Italy
State/province [16] 0 0
Milan
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Seoul
Country [18] 0 0
Netherlands
State/province [18] 0 0
Gouda
Country [19] 0 0
Poland
State/province [19] 0 0
Warsaw
Country [20] 0 0
Portugal
State/province [20] 0 0
Porto Salvo
Country [21] 0 0
Russian Federation
State/province [21] 0 0
Moscow
Country [22] 0 0
Singapore
State/province [22] 0 0
Singapore
Country [23] 0 0
South Africa
State/province [23] 0 0
Gauteng
Country [24] 0 0
Spain
State/province [24] 0 0
Barcelona
Country [25] 0 0
Sweden
State/province [25] 0 0
Bromma
Country [26] 0 0
Switzerland
State/province [26] 0 0
Geneva
Country [27] 0 0
Taiwan
State/province [27] 0 0
Taipei
Country [28] 0 0
Turkey
State/province [28] 0 0
Istanbul
Country [29] 0 0
Ukraine
State/province [29] 0 0
Kiev
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Guildford Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Regeneron Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Primary objective was to demonstrate overall survival improvement with aflibercept compared
to placebo in patients receiving docetaxel / prednisone for metastatic androgen-independent
prostate cancer (MAIPC).

The secondary objectives were:

- To assess the efficacy of aflibercept compared to placebo on other parameters such
prostate-specific antigen (PSA) level, cancer related pain, progression free survival
(PFS), tumor-based and skeletal events and health-related quality of life (HRQL);

- To assess the overall safety in both treatment arms;

- To determine the pharmacokinetics of intravenous (IV) aflibercept in this population;

- to determine immunogenicity of IV aflibercept.
Trial website
https://clinicaltrials.gov/show/NCT00519285
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications