Treating Patients With Metastatic Prostate Cancer Not Responding to Hormone and Chemotherapy
Phase I/II Trial of Epothilone Analog BMS-247550 (Ixabepilone), Mitoxantrone, and Prednisone in Hormone Refractory Prostate Cancer (HRPC) Patients Previously Treated With Chemotherapy
4 other identifiers
interventional
100
1 country
2
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2006
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2006
CompletedFirst Submitted
Initial submission to the registry
May 30, 2006
CompletedFirst Posted
Study publicly available on registry
May 31, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2010
CompletedResults Posted
Study results publicly available
October 31, 2017
CompletedOctober 31, 2017
October 1, 2017
4.6 years
May 30, 2006
June 2, 2017
October 2, 2017
Conditions
Outcome Measures
Primary Outcomes (3)
Proportion Responding to Treatment With of the Combination of Ixabepilone and Mitoxantrone Hydrochloride With Prednisone in Hormone Refractory Prostate Cancer Patients Who Have Had Prior Taxane Chemotherapy Based Upon a PSA Decline of > 50% (Phase II)
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% Prostate Specific Antigen (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. 58 patients were enrolled for phase II, two were ineligible so 56 patients were analyzed.
Every 3 courses until cancer progression/excessive toxicity or death
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. The cumulative grade 3 or higher adverse events for all dose levels are noted below and in the table of adverse events.
Every 21 days until cancer progression/excessive toxicity or death
Dose Limiting Toxicities for Each Dose Level of Ixabepilone, Mitoxantrone Hydrochloride, and Prednisone in Patients With Hormone-refractory Metastatic Prostate Cancer That Progressed During or After Taxane-based Chemotherapy (Phase I).
Cohorts of 3 patients will be enrolled at each dose level; if 1 dose limiting toxicity (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 maximum tolerated dose (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.
Course 1 (first 21 days)
Secondary Outcomes (1)
Time to Progression (Phase II)
Every 3 months until cancer progression/excessive toxicity or death
Study Arms (1)
Treatment (combination chemotherapy)
EXPERIMENTALPatients 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.
Interventions
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Histologically confirmed adenocarcinoma of the prostate
- Progressive metastatic disease (i.e., positive bone scan or measurable disease) despite castrate levels of testosterone (either from orchiectomy or luteinizing hormone-releasing hormone \[LHRH\] agonist therapy)
- Progressive disease after discontinuing hormonal therapy
- Progressive disease is based on any of the following\*:
- Transaxial imaging
- Rise in prostate-specific antigen (PSA)
- Radionuclide bone scan (must show new metastatic lesions)
- Nonmeasurable or measurable disease
- For measurable disease, progression is defined by RECIST criteria
- Positive bone scan and elevated PSA required for nonmeasurable disease
- PSA evidence of progressive prostate cancer during or after first-line chemotherapy consists of a PSA level ≥ 2 ng/mL that has risen on ≥ 2 successive occasions ≥ 1 week apart
- Received ≥ 3 prior courses of paclitaxel- or docetaxel-based therapy, with disease progression documented during therapy or after cessation of therapy
- No more than 1 prior chemotherapy regimen
- Re-treatment with the same taxane-based regimen allowed
- Changes in prior chemotherapy regimen (addition of other agents) for disease progression are considered 2 chemotherapy regimens, and are not allowed
- +32 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94143-0875, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
Related Publications (2)
Rosenberg JE, Ryan CJ, Weinberg VK, Smith DC, Hussain M, Beer TM, Ryan CW, Mathew P, Pagliaro LC, Harzstark AL, Sharib J, Small EJ. Phase I study of ixabepilone, mitoxantrone, and prednisone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel-based therapy: a study of the department of defense prostate cancer clinical trials consortium. J Clin Oncol. 2009 Jun 10;27(17):2772-8. doi: 10.1200/JCO.2008.19.8002. Epub 2009 Apr 6.
PMID: 19349545RESULTHarzstark AL, Rosenberg JE, Weinberg VK, Sharib J, Ryan CJ, Smith DC, Pagliaro LC, Beer TM, Liu G, Small EJ. Ixabepilone, mitoxantrone, and prednisone for metastatic castration-resistant prostate cancer after docetaxel-based therapy: a phase 2 study of the Department Of Defense Prostate Cancer Clinical Trials Consortium. Cancer. 2011 Jun 1;117(11):2419-25. doi: 10.1002/cncr.25810. Epub 2010 Dec 29.
PMID: 24048789RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Andrea Harzstark, M.D.
- Organization
- Oakland Medical Center
Study Officials
- PRINCIPAL INVESTIGATOR
Andrea Harzstark
University of California San Francisco Medical Center-Mount Zion
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 30, 2006
First Posted
May 31, 2006
Study Start
April 1, 2006
Primary Completion
November 1, 2010
Study Completion
November 1, 2010
Last Updated
October 31, 2017
Results First Posted
October 31, 2017
Record last verified: 2017-10