Castration-Resistant Prostate Cancer
Conditions
Interventions
Sponsors
Bristol-Myers Squibb
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Subjects must have signed an informed consent document stating that they understand the investigational nature of the proposed treatment. History of histologically diagnosed prostate cancer. Evidence of metastatic disease by any 1 of the following modalities: CT scan, MRI, bone scan, or skeletal survey. Evidence of progression, as defined by 1 of the following: Rising PSA values at least 1 week apart with the final value being >= 2 ng/mL,or Progression of measurable nodal or visceral disease: Nodal lesions must be >= 20 mm Visceral lesions must be measurable per RECIST criteria, or Two or more new lesions appearing on a bone scan compared with a prior scan, or Local recurrence in the prostate or prostate bed. Maintaining castrate status: Subjects who have not undergone surgical orchiectomy should have received and continue on medical therapies [eg, gonadotropin releasing hormone analogs (GnRH/LHRH analogs)] to maintain castrate levels of serum testosterone = 3,000/mm3. ANC >= 1,500/mm3. Platelet count >= 100,000/mm3. Creatinine <= 1.5 x upper limits of normal. Bilirubin <= upper limit of normal (does not apply for subjects with Gilbert’s Disease). SGOT (AST) <= 2.5 x upper limits of normal. SGPT (ALT) <= 2.5 x upper limits of normal. Men only, at least 18 years old.
Exclusion criteria
Exclusion criteria: Women. Sexually active fertile men not using effective birth control if their partners are WOCBP. Subjects with active brain metastases or leptomeningeal metastases are excluded from this clinical trial. Clinically significant cardiovascular disease, including myocardial infarction or ventricular tachyarrhythmia within 6 months, prolonged QTc > 450 msec, ejection fraction (EF) = 2. Subjects with a “currently active” second malignancy other than non-melanoma skin cancers are not to be enrolled into the study. Subjects are not considered to have a “currently active” malignancy if they have completed therapy and are now considered (by their physician) to be at less than 30% risk for relapse. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. HIV-positive subjects receiving combination anti-retroviral therapy. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the investigational agents. Subjects may not be receiving any other investigational agents for the treatment of prostate cancer. No prior cytotoxic chemotherapy in the metastatic setting, with the exception of estramustine. Subjects may continue on a daily multi-vitamin but all other herbal, alternative and food supplements (eg, PC-Spes, Saw Palmetto, St John’s Wort) must be discontinued before enrollment into the study. Ketoconazole must be discontinued 4 weeks prior to starting study therapy. Anti-androgens should be discontinued prior to starting study therapy. Subjects with a history of response to an anti-androgen and subsequent progression while on that anti-androgen should be assessed for anti-androgen withdrawal response for 4 weeks. Observation for anti-androgen withdrawal response is not necessary for subjects who have never responded to anti-androgens. Bisphosphonates must not be initiated within 28 days prior to starting study therapy. QT prolonging agents strongly associated with torsade de pointes. Prisoners or subjects who are involuntarily incarcerated. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival will be defined as the time from the date of randomization to the date of death. If the subject did not die, survival will be censored on the last date the subject was known to be alive.;The primary endpoint in this study is Overall Survival and will be based on the Intention To Treat (ITT) population. The primary analysis of Overall Survival will be a comparison between the 2 treatment arms using a two-sided, alpha = 0.0463 (0.0002, 0.012 for the first and second interim analyses respectively) log-rank test, stratified by ECOG - Eastern Cooperative Oncology Group performance status (0 - 1 vs 2), baseline biphosphonates intake (yes or no), and urinary N-telopeptide value (= 60 nmol/mmol creatinine). The alpha level is adjusted for 2 planned interim analyses using the O’Brien-Fleming alpha spending function. Further analysis of Overall Survival will include the computation of hazard ratios and the estimation of survival functions. The survival hazard ratio of dasatinib in combination with docetaxel and prednisone to placebo in combination with docetaxel and prednisone and an associated two-sided 95.37% (99.98% and 98.8% for the first and second interim analyses respectively) confidence interval, will be computed using unadjusted and adjusted Cox proportional hazards model stratified by ECOG - Eastern Cooperative Oncology Group performance status (0 - 1 vs 2), baseline bisphosphonate intake (yes/no), and urinary N-telopeptide value (= 60 nmol/mmol creatinine). The adjusted Cox proportional hazards model will include treatment and pre-specified prognostic factors including age (= 70 years), presence of bone metastases (any bone metastases vs no bone mestastases), baseline alkaline phosphatase, type of progression (PSA (prostatic specific antigen), measurable disease, bone scan progression), number of metastases sites (= 2), baseline hemoglobin, and baseline PSA (prostatic specific antigen)level. The proportional hazards assumption will be assessed | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary efficacy endpoints include rate of uNTx (Urinary N-Telopeptide) change from baseline, time to first skeletal-related event, change in pain intensity, time to PSA (prostatic specific antigen) progression, objective tumor response rate, and rate of stable disease by bone scans. Secondary efficacy endpoints will be tested hierarchically. Time to first skeletal-related event and time to PSA (prostatic specific antigen) progression in each arm will be estimated using the Kaplan-Meier product limit method. A two-sided 95% confidence interval for median TFSRE (time to free Slekeletal-Related Event) and time to PSA (prostatic specific antigen) progression will be computed using the methods of Brookmeyer and Crowley. TFSRE (time to free Slekeletal-Related Event) and time to PSA (prostatic specific antigen) progression will also be compared between treatment arms with a two-sided, alpha= 05 level, log-rank test, stratified by ECOG - Eastern Cooperative Oncology Group performance status (0 - 1 vs 2), baseline bisphosphonate intake (yes/no), and urinary N-telopeptide value (=60 nmol/mmol creatinine). The proportion change in pain intensity, the stable disease by bone scans rate and the objective tumor response rate (RR) will be summarized for the 2 treatment arms with a Cochran-Mantel-Haenszel (CMH) test, an associated odds ratio estimate and a 95% confidence interval, stratified by ECOG - Eastern Cooperative Oncology Group performance status (0 - 1 vs 2), baseline bisphosphonate intake (yes/no), and urinary N-telopeptide value (= 60 nmol/mmol creatinine). Secondary efficacy analyses will be performed at the time final survival analysis is performed. | — |
Countries
Australia, Brazil, Canada, Czech Republic, Finland, France, Germany, Greece, Hungary, India, Italy, Korea, Republic of, Norway, Poland, Romania, Russian Federation, South Africa, Switzerland, United Kingdom, United States
Contacts
Public ContactJuliana Castro
Bristol-Myers Squibb
Outcome results
None listed