This partially randomized phase I/II trial studies cabazitaxel with or without carboplatin in treating patients with previously treated prostate cancer that has spread to other areas of the body and does not respond to treatment with hormones. Drugs used in chemotherapy, such as cabazitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving cabazitaxel alone or with carboplatin is more effective in treating prostate cancer.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dosage (MTD) of cabazitaxel-carboplatin in the phase I portion of the study. II. To evaluate progression free survival achieved with cabazitaxel-carboplatin versus cabazitaxel alone in men with metastatic castration resistant prostate cancer (mCRPC) in the phase II portion of the study. SECONDARY OBJECTIVES: I. To assess prostate-specific antigen (PSA) response rate (percentage of patients with \> 50 % decline). II. To correlate changes in bone specific alkaline phosphatase and urine n-telopeptides with response. III. To evaluate overall survival. IV. To evaluate safety and toxicity. V. To evaluate influence of the anaplastic phenotype on response to therapy. VI. To collect and archive serum, plasma, and urine samples in study patients for later hypothesis generating associations. OUTLINE: This is a phase I, dose-escalation study followed by a randomized phase II study. PHASE I: Patients receive cabazitaxel intravenously (IV) over 60-90 minutes and carboplatin IV over 60-90 minutes on day 1. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. PHASE II: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cabazitaxel IV over 60-90 minutes on day 1. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive cabazitaxel IV over 60-90 minutes and carboplatin IV over 60-90 minutes on day 1. Treatment repeats every 21 days for up to 10 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
170
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
M D Anderson Cancer Center
Houston, Texas, United States
Maximum Tolerated Dosage (MTD) of Cabazitaxel-carboplatin in the Phase I Portion of Study
The MTD was defined as the highest dose cohort studied in which one of six or fewer patients experienced a dose-limiting toxicity.
Time frame: 6 months
Progression Free Survival (PFS) of Cabazitaxel-carboplatin Versus Cabazitaxel in the Phase II Portion of Study
PFS is the time from the first dose until progression of disease or death, whichever comes first. PFS times will be estimated using the Kaplan-Meier method.
Time frame: From the first dose until progression of disease or death, whichever comes first, up to 5 years
Prostate Specific Antigen (PSA) Response Rate
Percentage of participants with a greater than 50% decrease in measurable values of PSA during treatment from their baseline PSA.
Time frame: 5 years
Bone-Specific Alkaline Phosphatase Response
Percentage of participants with a greater than 50% decrease in measurable values of bone-specific alkaline phosphatase during treatment from their baseline values
Time frame: 5 years
Urine N-Telopeptides Response
Percentage of participants with a greater than 50% decrease in measurable values of urine n-telopeptides during treatment from their baseline values.
Time frame: 5 years
Overall Survival (OS)
Time from date of treatment start until date of death due to any cause or last follow up.
Time frame: Time from date of treatment start until date of death due to any cause or last follow up, up to 5 years
Phase II Most Common Grade 3-5 Adverse Events
Grade 3: Serious reaction which requires medical treatment Grade 4: Life threatening. Grade 5 Death.
Time frame: Time from date of treatment start until date of death due to any cause or last follow up, up to 5 years
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