Clinical trial NCT00519285: Aflibercept in Combination With Docetaxel in Metastatic Androgen Independent Prostate Cancer
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostatic Neoplasms
Neoplasm Metastasis
Keywords: metastatic
prostate
cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2007-08-22
Enrollment: 1224
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Histologically- or cytologically-confirmed prostate adenocarcinoma;
* Metastatic disease;
* Progressive disease while receiving hormonal therapy or after surgical castration;
* Effective castration.

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.

Primary outcomes:
measure: Overall Survival Time
timeFrame: From randomization up to the cut-off date (median follow-up of 35.4 months)
Secondary outcomes:
measure: Prostate Specific Antigen Response Rate
timeFrame: Before randomization (baseline) then every 3 weeks up to PSA progression (≥25% increase) or the cut-off date, whichever occurred first
measure: Time to Skeletal Related Events
timeFrame: From randomization up to the cut-off date (median follow-up of 35.4 months)
measure: Progression Free Survival Time
timeFrame: From randomization up to the cut-off date (median follow-up of 35.4 months)
measure: Tumor Response Rate in Participants With Measurable Disease
timeFrame: Before randomization (baseline) then every 3 months up to tumor progression (≥25% increase) or the cut-off date, whichever occurred first
measure: Prostate Specific Antigen Progression-free Survival Time
timeFrame: From randomization up to the cut-off date (median follow-up of 35.4 months)
measure: Pain Progression-free Survival Time
timeFrame: From randomization up to the cut-off date (median follow-up of 35.4 months)
measure: Pain Response Rate
timeFrame: Before randomization (baseline) then every 3 weeks up to pain progression or the cut-off date, whichever occurred first
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Prostate Total Score as a Measure of Health Related Quality of Life
timeFrame: Before randomization (baseline) then every 3 weeks until disease progression or administration of further antitumor therapy, whichever came first
measure: Number of Participants With Adverse Events as a Measure of Safety
timeFrame: 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
measure: Number of Participants With Positive Anti-aflibercept Antibody Levels as a Measure of Immunogenicity of Aflibercept
timeFrame: 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
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Buenos Aires
country: Argentina
facility: Sanofi-Aventis Administrative Office
city: Macquarie Park
country: Australia
facility: Sanofi-Aventis Administrative Office
city: Diegem
country: Belgium
facility: Sanofi-Aventis Administrative Office
city: Sao Paulo
country: Brazil
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Providencia Santiago
country: Chile
facility: Sanofi-Aventis Administrative Office
city: City of Zagreb
country: Croatia
facility: Sanofi-Aventis Administrative Office
city: Praha
country: Czech Republic
facility: Sanofi-Aventis Administrative Office
city: Horsholm
country: Denmark
facility: Sanofi-Aventis Administrative Office
city: Tallinn
country: Estonia
facility: Sanofi-Aventis Administrative Office
city: Paris
country: France
facility: Sanofi-Aventis Administrative Office
city: Frankfurt
country: Germany
facility: Sanofi-Aventis Administrative Office
city: Hong Kong
country: Hong Kong
facility: Sanofi-Aventis Administrative Office
city: Budapest
country: Hungary
facility: Sanofi-Aventis Administrative Office
city: Natanya
country: Israel
facility: Sanofi-Aventis Administrative Office
city: Milan
country: Italy
facility: Sanofi-Aventis Administrative Office
city: Seoul
country: Korea, Republic of
facility: Sanofi-Aventis Administrative Office
city: Gouda
country: Netherlands
facility: Sanofi-Aventis Administrative Office
city: Warsaw
country: Poland
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis Administrative Office
city: Singapore
country: Singapore
facility: Sanofi-Aventis Administrative Office
city: Gauteng
country: South Africa
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Bromma
country: Sweden
facility: Sanofi-Aventis Administrative Office
city: Geneva
country: Switzerland
facility: Sanofi-Aventis Administrative Office
city: Taipei
country: Taiwan
facility: Sanofi-Aventis Administrative Office
city: Istanbul
country: Turkey
facility: Sanofi-Aventis Administrative Office
city: Kiev
country: Ukraine
facility: Sanofi-Aventis Administrative Office
city: Guildford Surrey
country: United Kingdom
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.