Ixabepilone Compared With Mitoxantrone and Prednisone in Treating Patients With Refractory Metastatic Prostate Cancer

Tracking Information
First Submitted Date ICMJE	April 7, 2003
First Posted Date ICMJE	April 9, 2003
Last Update Posted Date	February 23, 2017
Study Start Date ICMJE	March 2003
Actual Primary Completion Date	October 1, 2007 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 14, 2013)	Response to the randomized treatment as determined by > 50% PSA response as measured by RECIST criteria [ Time Frame: Up to 3 months ]; The frequency of response with 95% confidence limits for a binomial outcome will be calculated.
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00058084 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: January 14, 2013)	Frequency of any toxicity by grade [ Time Frame: Up to 3 months ]; Response duration [ Time Frame: From the date PR or CR is first determined until the first evidence of progressive disease, assessed up to 3 months ]Will be estimated using the Kaplan-Meier product limit method.; Time to progressive disease [ Time Frame: From the date protocol therapy is started until the first evidence of progressive disease, assessed up to 3 months ]Will be estimated using the Kaplan-Meier product limit method.; Frequency of response to third-line (crossover) therapy [ Time Frame: Up to 3 months ]Estimates of response to third line treatment along with 95% confidence intervals will be calculated.
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Ixabepilone Compared With Mitoxantrone and Prednisone in Treating Patients With Refractory Metastatic Prostate Cancer
Official Title ICMJE	A Randomized Phase II Study Of BMS 247550 Or Mitoxantrone And Prednisone In Patients With Taxane Resistant Hormone Refractory Prostate Cancer
Brief Summary	This randomized phase II trial is studying ixabepilone to see how well it works compared to mitoxantrone and prednisone in treating patients with metastatic prostate cancer that has not responded to paclitaxel, docetaxel, or hormone therapy. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Some tumors become resistant to chemotherapy drugs. Ixabepilone may reduce resistance to the drugs and allow the tumor cells to be killed. It is not yet known which chemotherapy regimen is more effective in treating metastatic prostate cancer
Detailed Description	PRIMARY OBJECTIVES: I. Determine the efficacy of ixabepilone (BMS-247550) vs mitoxantrone and prednisone, in terms of decline in prostate-specific antigen (PSA) levels, in patients with taxane-resistant, hormone-refractory metastatic prostate cancer. SECONDARY OBJECTIVES: I. Determine the safety of these regimens in these patients. II. Determine the objective response rate in patients with measurable disease who are treated with these regimens. III. Determine the clinical activity of each of these regimens after crossover in patients who experience disease progression on their originally assigned treatment arm and switch to the other treatment arm. OUTLINE: This is a randomized, crossover, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1 or 2). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive ixabepilone (BMS-247550) IV over 3 hours on day 1. ARM II: Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21.In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients who progress while on treatment after at least 2 courses or discontinue treatment for any other reason may cross over to the other arm and receive treatment as above, beginning within 12 weeks of last study treatment on original arm. Patients are followed every 3 months.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Adenocarcinoma of the Prostate; Recurrent Prostate Cancer; Stage IV Prostate Cancer
Intervention ICMJE	Drug: ixabepilone Given IV Other Names: BMS-247550 epothilone B lactam Ixempra; Drug: mitoxantrone hydrochloride Given IV Other Names: CL 232315 DHAD DHAQ Novantrone; Drug: prednisone Given orally Other Names: DeCortin Deltra
Study Arms	Experimental: Arm I Patients receive ixabepilone (BMS-247550) IV over 3 hours on day 1. Intervention: Drug: ixabepilone; Experimental: Arm II Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Interventions: Drug: mitoxantrone hydrochloride Drug: prednisone
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: January 14, 2013)	80
Original Enrollment ICMJE	Not Provided
Study Completion Date	Not Provided
Actual Primary Completion Date	October 1, 2007 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate; Metastatic disease (positive bone scan or measurable disease); Progressive hormone-refractory disease Based on 1 of the following: Transaxial imaging Rise in prostate-specific antigen (PSA) Radionuclide bone scan Must have undergone primary hormonal treatment (e.g., orchiectomy or gonadotropin-releasing hormone analog with or without an antiandrogen) and demonstrated disease progression after antiandrogen discontinuation as defined below: Two consecutive rising PSA values, obtained at least 2 weeks apart, or documented osseous or soft tissue progression For patients receiving flutamide, at least 1 PSA value must be obtained at least 4 weeks after flutamide discontinuation For patients receiving bicalutamide or nilutamide, at least 1 PSA value must be obtained at least 6 weeks after antiandrogen discontinuation Ineligible if sole manifestation of progression is an increase in disease-related symptoms; Meets 1 of the following criteria: Measurable disease and an elevated PSA Nonmeasurable disease and an elevated PSA, as follows: Positive bone scan PSA level at least 5 ng/mL, with increases on at least 2 successive occasions at least 2 weeks apart New metastatic lesions by radionuclide bone scan; Must have received at least 2 courses of paclitaxel- or docetaxel-based therapy, with disease progression documented during therapy or no more than 60 days after cessation of therapy*; Testosterone < 50 ng/dL; No known active brain metastases; Performance status - ECOG 0-2; At least 12 weeks; Granulocyte count ≥ 1,500/mm^3; Platelet count ≥ 100,000/mm^3; Bilirubin < 1.5 times upper limit of normal (ULN); AST and ALT < 3 times ULN; Creatinine ≤ 1.5 times ULN; Creatinine clearance > 40 mL/min; Ejection fraction ≥ lower limit of normal by MUGA or echocardiogram; No myocardial infarction within the past 6 months; No significant cardiovascular disease; No New York Heart Association class III or IV congestive heart failure; No active angina pectoris; Fertile patients must use effective contraception before, during, and for 3 months after study therapy; No prior hypersensitivity reaction to agents containing Cremophor®EL; No serious infection; No nonmalignant medical illnesses that are uncontrolled or whose control would be jeopardized by complications of study therapy; No psychiatric illness or social situation that would preclude study compliance; No motor or sensory neuropathy grade 2 or greater; No "currently active" second malignancy except nonmelanoma skin cancer Patients are not considered to have a "currently active" malignancy provided they have completed therapy and are considered to have less than a 30% risk of relapse; No concurrent prophylactic colony-stimulating factors for myelosuppression; See Disease Characteristics; No more than 1 prior chemotherapy regimen; No prior mitoxantrone or epothilone; No other concurrent chemotherapy; See Disease Characteristics; At least 4 weeks since prior antiandrogens (e.g., flutamide) (6 weeks for bicalutamide or nilutamide) Patients must continue primary androgen deprivation therapy with luteinizing hormone-releasing hormone agonist during study if prior orchiectomy was not performed; At least 4 weeks since prior systemic (including oral) corticosteroids except corticosteroids as part of first-line chemotherapy tapered off over 10-14 days prior to study entry; At least 4 weeks since any prior hormonal therapy, including megestrol or finasteride; No other concurrent systemic steroids; At least 4 weeks since prior radiotherapy; More than 8 weeks since prior radiopharmaceuticals (e.g., strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium); No concurrent radiotherapy; See Disease Characteristics; At least 4 weeks since prior herbal products known to decrease PSA levels (e.g., Saw Palmetto or PC-SPES); More than 4 weeks since other prior antiprostate cancer therapy; More than 4 weeks since prior systemic therapies for prostate cancer; No other concurrent investigational agents
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00058084
Other Study ID Numbers ICMJE	NCI-2012-02526; UCSF-02555; N01CM62206 ( U.S. NIH Grant/Contract ); CDR0000285731 ( Registry Identifier: PDQ (Physician Data Query) )
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	National Cancer Institute (NCI)
Study Sponsor ICMJE	National Cancer Institute (NCI)
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Jonathan Rosenberg University of California, San Francisco
PRS Account	National Cancer Institute (NCI)
Verification Date	February 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP