Ixabepilone, Mitoxantrone Hydrochloride, and Prednisone in Treating Patients With Metastatic Prostate Cancer That Did Not Respond to Hormone Therapy and Chemotherapy
This phase I/II trial is studying the side effects and best dose of ixabepilone and mitoxantrone hydrochloride when given together with prednisone and to see how well they work in treating patients with metastatic prostate cancer that did not respond to hormone therapy and chemotherapy. Drugs used in chemotherapy, such as ixabepilone, mitoxantrone hydrochloride, and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells
Adenocarcinoma of the Prostate
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Drug: mitoxantrone hydrochloride
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Trial of Epothilone Analog BMS-247550 (Ixabepilone), Mitoxantrone, and Prednisone in Hormone Refractory Prostate Cancer Patients Previously Treated With Chemotherapy|
- Safety of the combination of ixabepilone, mitoxantrone hydrochloride, and prednisone in patients with hormone-refractory metastatic prostate cancer that progressed during or after taxane-based chemotherapy (phase I) [ Time Frame: Every 21 days ] [ Designated as safety issue: Yes ]This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 for adverse event monitoring and reporting. Toxicities will be tabulated by grade for each dose cohort and overall for all patients accrued to the phase I study.
- Maximum tolerated dose of the combination of ixabepilone, mitoxantrone hydrochloride, and prednisone in patients with hormone-refractory metastatic prostate cancer that progressed during or after taxane-based chemotherapy (phase I) [ Time Frame: Course 1 (first 21 days) ] [ Designated as safety issue: Yes ]Cohorts of 3 patients will be enrolled at each dose level; if 1 DLT is observed then the cohort will be expanded to 6 patients. If a second DLT is observed, the previous dose level will be considered the MTD. If all observed DLT are due to neuropathy (specific to ixabepilone), then we would consider the previous dose level of Ixabepilone the MTD for that drug, and escalate mitoxantrone hydrochloride as described above to a maximum dose of 12 mg/m^2. Toxicities will be tabulated by grade for each dose cohort and overall for all patients accrued to the phase I study.
- Proportion responding to treatment with of the combination of ixabepilone and mitoxantrone hydrochloride with prednisone in HRPC patients who have had prior taxane chemotherapy based upon a PSA decline of > 50% (phase II) [ Time Frame: Every 3 courses ] [ Designated as safety issue: No ]Descriptive statistics will be calculated to characterize the disease and treatment factors including the proportion responding with a 95% confidence interval. If accrual is completed and more than 15 of 58 patients show > 50% PSA declines after 3 courses, then the null hypothesis of a 20% response proportion will be rejected. PSA declines for individual patients will be plotted in the form of a waterfall diagram of maximal PSA declines.
- Time to progression (phase II) [ Time Frame: Every 3 months ] [ Designated as safety issue: Yes ]Estimated using the Kaplan-Meier product limit method.
|Study Start Date:||April 2006|
|Primary Completion Date:||November 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (combination chemotherapy)
Patients receive mitoxantrone hydrochloride IV over 30 minutes and ixabepilone IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.
Drug: mitoxantrone hydrochloride
Other Names:Drug: ixabepilone
Other Names:Drug: prednisone
I. Determine the maximum tolerated dose (MTD) and dose-limiting toxicities of the combination of ixabepilone, mitoxantrone hydrochloride, and prednisone in patients with hormone-refractory metastatic prostate cancer that progressed during or after taxane-based chemotherapy. (Phase I) II. Assess the efficacy, as measured by reduction in prostate-specific antigen, of this regimen in these patients. (Phase II)
I. Evaluate the overall safety of this regimen as second-line chemotherapy in these patients.
II. Evaluate the objective response rate in patients treated with this regimen.
OUTLINE: This is a multicenter, phase I, open label, dose-escalation study of mitoxantrone hydrochloride and ixabepilone followed by a phase II study.
PHASE I: Patients receive mitoxantrone hydrochloride intravenously (IV) over 30 minutes and ixabepilone IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of mitoxantrone hydrochloride and ixabepilone until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
PHASE II: Patients receive mitoxantrone hydrochloride and ixabepilone at the MTD determined in phase I and prednisone as in phase I.
After completion of study treatment, patients are followed every 3 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00331344
|United States, California|
|UCSF Helen Diller Family Comprehensive Cancer Center|
|San Francisco, California, United States, 94143-0875|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Andrea Harzstark||University of California San Francisco Medical Center-Mount Zion|