Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.
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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/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
Query!
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
Query!
Secondary ID [1]
0
0
2006-004756-20
Query!
Secondary ID [2]
0
0
EFC6546
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
VENICE
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms
0
0
Query!
Neoplasm Metastasis
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Prostate
Query!
Intervention/exposure
Study type
Interventional
Query!
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
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Overall Survival Time
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
From randomization up to the cut-off date (median follow-up of 35.4 months)
Query!
Secondary outcome [1]
0
0
Prostate Specific Antigen Response Rate
Query!
Assessment method [1]
0
0
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.
Query!
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
Query!
Secondary outcome [2]
0
0
Time to Skeletal Related Events
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
From randomization up to the cut-off date (median follow-up of 35.4 months)
Query!
Secondary outcome [3]
0
0
Progression Free Survival Time
Query!
Assessment method [3]
0
0
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.
Query!
Timepoint [3]
0
0
From randomization up to the cut-off date (median follow-up of 35.4 months)
Query!
Secondary outcome [4]
0
0
Tumor Response Rate in Participants With Measurable Disease
Query!
Assessment method [4]
0
0
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.
Query!
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
Query!
Secondary outcome [5]
0
0
Prostate Specific Antigen Progression-free Survival Time
Query!
Assessment method [5]
0
0
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.
Query!
Timepoint [5]
0
0
From randomization up to the cut-off date (median follow-up of 35.4 months)
Query!
Secondary outcome [6]
0
0
Pain Progression-free Survival Time
Query!
Assessment method [6]
0
0
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.
Query!
Timepoint [6]
0
0
From randomization up to the cut-off date (median follow-up of 35.4 months)
Query!
Secondary outcome [7]
0
0
Pain Response Rate
Query!
Assessment method [7]
0
0
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.
Query!
Timepoint [7]
0
0
Before randomization (baseline) then every 3 weeks up to pain progression or the cut-off date, whichever occurred first
Query!
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
Query!
Assessment method [8]
0
0
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.
Query!
Timepoint [8]
0
0
Before randomization (baseline) then every 3 weeks until disease progression or administration of further antitumor therapy, whichever came first
Query!
Secondary outcome [9]
0
0
Number of Participants With Adverse Events as a Measure of Safety
Query!
Assessment method [9]
0
0
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).
Query!
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
Query!
Secondary outcome [10]
0
0
Number of Participants With Positive Anti-aflibercept Antibody Levels as a Measure of Immunogenicity of Aflibercept
Query!
Assessment method [10]
0
0
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.
Query!
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
Query!
Eligibility
Key inclusion criteria
* Histologically- or cytologically-confirmed prostate adenocarcinoma;
* Metastatic disease;
* Progressive disease while receiving hormonal therapy or after surgical castration;
* Effective castration.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Males
Query!
Can healthy volunteers participate?
No
Query!
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.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Blinded (masking used)
Query!
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people analysing the results/data
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 3
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/08/2007
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
1/04/2012
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
1224
Query!
Recruitment in Australia
Recruitment state(s)
Query!
Recruitment hospital [1]
0
0
Sanofi-Aventis Administrative Office - Macquarie Park
Query!
Recruitment postcode(s) [1]
0
0
- Macquarie Park
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
New Jersey
Query!
Country [2]
0
0
Argentina
Query!
State/province [2]
0
0
Buenos Aires
Query!
Country [3]
0
0
Belgium
Query!
State/province [3]
0
0
Diegem
Query!
Country [4]
0
0
Brazil
Query!
State/province [4]
0
0
Sao Paulo
Query!
Country [5]
0
0
Canada
Query!
State/province [5]
0
0
Laval
Query!
Country [6]
0
0
Chile
Query!
State/province [6]
0
0
Providencia Santiago
Query!
Country [7]
0
0
Croatia
Query!
State/province [7]
0
0
City of Zagreb
Query!
Country [8]
0
0
Czech Republic
Query!
State/province [8]
0
0
Praha
Query!
Country [9]
0
0
Denmark
Query!
State/province [9]
0
0
Horsholm
Query!
Country [10]
0
0
Estonia
Query!
State/province [10]
0
0
Tallinn
Query!
Country [11]
0
0
France
Query!
State/province [11]
0
0
Paris
Query!
Country [12]
0
0
Germany
Query!
State/province [12]
0
0
Frankfurt
Query!
Country [13]
0
0
Hong Kong
Query!
State/province [13]
0
0
Hong Kong
Query!
Country [14]
0
0
Hungary
Query!
State/province [14]
0
0
Budapest
Query!
Country [15]
0
0
Israel
Query!
State/province [15]
0
0
Natanya
Query!
Country [16]
0
0
Italy
Query!
State/province [16]
0
0
Milan
Query!
Country [17]
0
0
Korea, Republic of
Query!
State/province [17]
0
0
Seoul
Query!
Country [18]
0
0
Netherlands
Query!
State/province [18]
0
0
Gouda
Query!
Country [19]
0
0
Poland
Query!
State/province [19]
0
0
Warsaw
Query!
Country [20]
0
0
Portugal
Query!
State/province [20]
0
0
Porto Salvo
Query!
Country [21]
0
0
Russian Federation
Query!
State/province [21]
0
0
Moscow
Query!
Country [22]
0
0
Singapore
Query!
State/province [22]
0
0
Singapore
Query!
Country [23]
0
0
South Africa
Query!
State/province [23]
0
0
Gauteng
Query!
Country [24]
0
0
Spain
Query!
State/province [24]
0
0
Barcelona
Query!
Country [25]
0
0
Sweden
Query!
State/province [25]
0
0
Bromma
Query!
Country [26]
0
0
Switzerland
Query!
State/province [26]
0
0
Geneva
Query!
Country [27]
0
0
Taiwan
Query!
State/province [27]
0
0
Taipei
Query!
Country [28]
0
0
Turkey
Query!
State/province [28]
0
0
Istanbul
Query!
Country [29]
0
0
Ukraine
Query!
State/province [29]
0
0
Kiev
Query!
Country [30]
0
0
United Kingdom
Query!
State/province [30]
0
0
Guildford Surrey
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Sanofi
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Commercial sector/industry
Query!
Name [1]
0
0
Regeneron Pharmaceuticals
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Ethics approval
Ethics application status
Query!
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.
Query!
Trial website
https://clinicaltrials.gov/study/NCT00519285
Query!
Trial related presentations / publications
Tannock IF, Fizazi K, Ivanov S, Karlsson CT, Flechon A, Skoneczna I, Orlandi F, Gravis G, Matveev V, Bavbek S, Gil T, Viana L, Aren O, Karyakin O, Elliott T, Birtle A, Magherini E, Hatteville L, Petrylak D, Tombal B, Rosenthal M; VENICE investigators. Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial. Lancet Oncol. 2013 Jul;14(8):760-8. doi: 10.1016/S1470-2045(13)70184-0. Epub 2013 Jun 4. van Soest RJ, Templeton AJ, Vera-Badillo FE, Mercier F, Sonpavde G, Amir E, Tombal B, Rosenthal M, Eisenberger MA, Tannock IF, de Wit R. Neutrophil-to-lymphocyte ratio as a prognostic biomarker for men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy: data from two randomized phase III trials. Ann Oncol. 2015 Apr;26(4):743-749. doi: 10.1093/annonc/mdu569. Epub 2014 Dec 15. de Liano AG, Reig O, Mellado B, Martin C, Rull EU, Maroto JP. Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer. Br J Cancer. 2014 Apr 29;110(9):2201-8. doi: 10.1038/bjc.2014.189. Epub 2014 Apr 10.
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Clinical Sciences & Operations
Query!
Address
0
0
Sanofi
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
Type
Citations or Other Details
Journal
Tannock IF, Fizazi K, Ivanov S, Karlsson CT, Flech...
[
More Details
]
Results are available at
https://clinicaltrials.gov/study/NCT00519285
Download to PDF