Phase I/II Trial of Epothilone Analog BMS-247550 (Ixabepilone), Mitoxantrone, and Prednisone in Hormone Refractory Prostate Cancer Patients Previously Treated With Chemotherapy
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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)
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.
Every 21 days
University of California San Francisco Medical Center-Mount Zion
United States: Food and Drug Administration
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|