Aflibercept in Combination With Docetaxel in Metastatic Androgen Independent Prostate Cancer (VENICE)

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00519285
First received: August 21, 2007
Last updated: August 2, 2013
Last verified: August 2013
Results First Received: April 25, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Conditions: Prostatic Neoplasms
Neoplasm Metastasis
Interventions: Drug: Aflibercept
Drug: Placebo (for aflibercept)
Drug: Docetaxel
Drug: Prednisone or Prednisolone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Between August 2007 and February 2010, a total of 1548 patients gave informed consent for this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Amongst these patients, a total of 324 were screening failures (primarily due to non-compliance with exclusion criteria) and did not get randomized.

Reporting Groups
  Description
Placebo Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily

Participant Flow:   Overall Study
    Placebo     Aflibercept  
STARTED     612 [1]   612 [1]
TREATED     604 [2]   605 [3]
Still Treated at Cut-off Date     1 [4]   2  
COMPLETED     0 [5]   0  
NOT COMPLETED     612     612  
Adverse Event                 127                 266  
Disease progression                 334                 186  
Physician Decision                 75                 47  
Participant's request                 53                 84  
Consent withdrawn                 4                 5  
Poor compliance to protocol                 5                 7  
Reason unspecified                 5                 8  
Not treated                 8                 7  
Treatment ongoing                 1                 2  
[1] Randomized
[2] Received at least part of one dose of placebo
[3] Received at least part of one dose of aflibercept
[4] The cut-off date for analysis was defined as 07 February 2012, date at which 873 deaths has occurred
[5] Participants were treated until progressive disease, unacceptable toxicity, or refusal of treatment



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Placebo, 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Aflibercept Aflibercept, 6 mg/kg 1 hour IV, immediately followed by docetaxel, 75 mg/m² 1 hour IV, every 3 weeks in combination with oral prednisone or prednisolone, 5 mg PO twice daily
Total Total of all reporting groups

Baseline Measures
    Placebo     Aflibercept     Total  
Number of Participants  
[units: participants]
  612     612     1224  
Age  
[units: Years]
Mean ± Standard Deviation
  67.6  ± 8.0     67.9  ± 7.8     67.8  ± 7.9  
Age, Customized  
[units: participants]
     
<65 years     225     195     420  
65-74 years     259     283     542  
≥75 years     128     134     262  
Gender, Customized  
[units: participants]
     
Male     612     612     1224  
Race/Ethnicity, Customized  
[units: participants]
     
Caucasian/White     552     560     1112  
Black     17     15     32  
Asian/Oriental     36     32     68  
Other     7     5     12  
Region of Enrollment  
[units: Participants]
     
Western Europe     219     227     446  
Eastern Europe     131     132     263  
North America     81     95     176  
South America     88     71     159  
Other region     93     87     180  
Body Surface Area (BSA)  
[units: m²]
Mean ± Standard Deviation
  2.0  ± 0.2     2.0  ± 0.2     2.0  ± 0.2  
Eastern Co-operative Group (ECOG) performance status [1]
[units: participants]
     
ECOG 0     285     283     568  
ECOG 1     299     303     602  
ECOG 2     28     26     54  
[1]

ECOG performance status:

  • 0 = Fully active, able to carry on all pre-disease performance without restriction
  • 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
  • 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours



  Outcome Measures
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1.  Primary:   Overall Survival Time   [ Time Frame: From randomization up to the cut-off date (median follow-up of 35.4 months) ]

2.  Secondary:   Prostate Specific Antigen Response Rate   [ Time Frame: Before randomization (baseline) then every 3 weeks up to PSA progression (≥25% increase) or the cut-off date, whichever occurred first ]

3.  Secondary:   Time to Skeletal Related Events   [ Time Frame: From randomization up to the cut-off date (median follow-up of 35.4 months) ]

4.  Secondary:   Progression Free Survival Time   [ Time Frame: From randomization up to the cut-off date (median follow-up of 35.4 months) ]

5.  Secondary:   Tumor Response Rate in Participants With Measurable Disease   [ Time Frame: Before randomization (baseline) then every 3 months up to tumor progression (≥25% increase) or the cut-off date, whichever occurred first ]

6.  Secondary:   Prostate Specific Antigen Progression-free Survival Time   [ Time Frame: From randomization up to the cut-off date (median follow-up of 35.4 months) ]

7.  Secondary:   Pain Progression-free Survival Time   [ Time Frame: From randomization up to the cut-off date (median follow-up of 35.4 months) ]

8.  Secondary:   Pain Response Rate   [ Time Frame: Before randomization (baseline) then every 3 weeks up to pain progression or the cut-off date, whichever occurred first ]

9.  Secondary:   Change From Baseline in Functional Assessment of Cancer Therapy-Prostate Total Score as a Measure of Health Related Quality of Life   [ Time Frame: Before randomization (baseline) then every 3 weeks until disease progression or administration of further antitumor therapy, whichever came first ]

10.  Secondary:   Number of Participants With Adverse Events as a Measure of Safety   [ Time Frame: 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 ]

11.  Secondary:   Number of Participants With Positive Anti-aflibercept Antibody Levels as a Measure of Immunogenicity of Aflibercept   [ Time Frame: 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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Pain response initially defined as a key secondary endpoint together with PSA response, time to occurence of SRE and PFS was finally considered as an exploratory endpoint in final statistical analysis plan.


  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Trial Transparency Team
Organization: Sanofi
e-mail: Contact-Us@sanofi.com


Publications of Results:
Publications automatically indexed to this study:

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00519285     History of Changes
Other Study ID Numbers: EFC6546, 2006-004756-20
Study First Received: August 21, 2007
Results First Received: April 25, 2013
Last Updated: August 2, 2013
Health Authority: United States: Food and Drug Administration