Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00003881

Trial Description

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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

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Trial Acronym

VENICE

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URL of the Trial

[---]*

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

The study consisted in 3-week treatment cycles until progressive disease, unacceptable
toxicity, or participant's refusal of further study treatment. After disease progression,
participants were to be followed every 3 months until death or the study cutoff date,
whichever came first.

The study cut-off date was event-driven and was defined as the date when 873 deaths had
occurred.

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Organizational Data

  •   DRKS00003881
  •   2012/04/30
  •   2007/08/21
  •   no
  •   [---]*
  •   [---]*
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Secondary IDs

  •   2006-004756-20 
  •   NCT00519285  (ClinicalTrials.gov)
  •   EFC6546  (Sanofi-Aventis)
  •   2006-004756-20 
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Health Condition or Problem studied

  •   Prostatic Neoplasms
  •   Neoplasm Metastasis
  •   C61 -  Malignant neoplasm of prostate
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Interventions/Observational Groups

  •   Drug: Aflibercept
  •   Drug: Placebo (for aflibercept)
  •   Drug: Docetaxel
  •   Drug: Prednisone or Prednisolone
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, caregiver, investigator/therapist
  •   Placebo
  •   Treatment
  •   Parallel
  •   III
  •   [---]*
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Primary Outcome

- Overall Survival Time; time frame: From randomization up to the cut-off date (median follow-up of 35.4 months); 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.

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Secondary Outcome

- 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; 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.
- Time to Skeletal Related Events; time frame: From randomization up to the cut-off date (median follow-up of 35.4 months); 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.
- Progression Free Survival Time; time frame: From randomization up to the cut-off date (median follow-up of 35.4 months); 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.
- 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; 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.
- Prostate Specific Antigen Progression-free Survival Time; time frame: From randomization up to the cut-off date (median follow-up of 35.4 months); 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.
- Pain Progression-free Survival Time; time frame: From randomization up to the cut-off date (median follow-up of 35.4 months); 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.
- Pain Response Rate; time frame: Before randomization (baseline) then every 3 weeks up to pain progression or the cut-off date, whichever occurred first; 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.
- 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; 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.
- 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; 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).
- 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; 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.

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Countries of Recruitment

  •   United States
  •   Argentina
  •   Australia
  •   Belgium
  •   Brazil
  •   Canada
  •   Chile
  •   Croatia
  •   Czech Republic
  •   Denmark
  •   Estonia
  •   France
  •   Germany
  •   Hong Kong
  •   Hungary
  •   Israel
  •   Italy
  •   Korea, Republic of
  •   Netherlands
  •   Poland
  •   Portugal
  •   Russian Federation
  •   Singapore
  •   South Africa
  •   Spain
  •   Sweden
  •   Switzerland
  •   Taiwan, Province of China
  •   Turkey
  •   Ukraine
  •   United Kingdom
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Locations of Recruitment

  •  
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Recruitment

  •   [---]*
  •   2007/08/31
  •   1224
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Male
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- Histologically- or cytologically-confirmed prostate adenocarcinoma;

- Metastatic disease;

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

- Effective castration.

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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.

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Addresses

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    • Sanofi
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    • Sanofi
    • Clinical Sciences & Operations 
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  • start of 1:1-Block address public-contact
    • Sanofi
    • Clinical Sciences & Operations 
    end of 1:1-Block address public-contact
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting complete, follow-up complete
  •   2012/04/01
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Trial Publications, Results and other Documents

  •   Tannock IF, Fizazi K, Ivanov S, Karlsson CT, Fléchon A, Skoneczna I, Orlandi F, Gravis G, Matveev V, Bavbek S, Gil T, Viana L, Arén 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.; 23742877
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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   9
  •   2016/01/14


* This entry means the parameter is not applicable or has not been set.