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Ixabepilone in Treating Patients With Metastatic Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00087139
First received: July 8, 2004
Last updated: January 3, 2013
Last verified: January 2013
History of Changes
  Purpose

RATIONALE: Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well ixabepilone works in treating patients with metastatic prostate cancer that has not responded to previous hormone therapy.


Condition Intervention Phase
Prostate Cancer
 Drug: ixabepilone
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of a Weekly Schedule of BMS-247550 for Patients With Hormone Refractory Prostate Cancer

Resource links provided by NLM:

Drug Information available for: Ixabepilone
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of Patients With PSA Response [ Time Frame: Every 4 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry ] [ Designated as safety issue: No ]
    PSA response is defined as a decline from baseline value by >=50%, or normalization of PSA (PSA < 0.2 ng/lm), confirmed by a second measurement >= 4 weeks later. The proportion of patients with PSA response was reported separately for 3 strata. Additional patients accrued to this study were not included in this analysis.


Secondary Outcome Measures:
  • Proportion of Patients With Measurable Disease Response (Best Overall Response) [ Time Frame: Every 8 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry ] [ Designated as safety issue: No ]
    Only patients with measurable disease were included in this analysis. The proportion of patients with measurable disease response (based on RECIST: Response Evaluation Criteria in Solid Tumors) was reported separately for 3 strata.

  • Duration of PSA Response [ Time Frame: Every 4 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry ] [ Designated as safety issue: No ]
    Duration of PSA response was defined as the time from the date of onset of PSA response until the date the criteria were met for PSA progression. Only patients with a PSA response were included in this analysis. The results were reported separately for 3 strata.

  • Duration of Measurable Disease Response [ Time Frame: Every 8 weeks during treatment; then every 3 months if <2 years from study entry; then every 6 months if 2-5 years from study entry ] [ Designated as safety issue: No ]
    Duration of measurable disease response was defined as the time from the date when measurement criteria were met for complete or partial response, whichever status was recorded first, until the first date that recurrent or progressive disease was objectively documented based on RECIST (Response Evaluation Criteria in Solid Tumors). Only patients with measurable disease response were included in this analysis.


Enrollment: 124
Study Start Date: September 2004
Estimated Study Completion Date: January 2014
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ixabepilone
There are three strata in this study: no prior chemo stratum, prior taxane stratum, and two prior chemo regimens stratum. All patients in the 3 strata received the same treatment, ixabepilone 20mg/m2 through IV over 1 hour on days 1, 8, and 15 (+/- 1 day) in 28-day cycles. Treatment continues until disease progression or unacceptable toxicity.
 Drug: ixabepilone

Premedication: (30-60 minutes prior to the infusion of ixabepilone)

  • Diphenhydramine (H1 receptor antagonist) 50 mg by mouth (PO)/IV
  • Ranitidine 50 mg IV or 150 mg PO (or H2 receptor antagonist equivalent, excluding cimetidine, which can inhibit Cytochrome P450 3A4 (CYP3A4) metabolism of ixabepilone).
Other Names:
  • BMS-247550
  • Ixempra

Detailed Description:

OBJECTIVES:

Primary

  • To determine the effect on percent with a 50% decrease in prostate specific antigen (PSA) response in patients with metastatic prostate cancer who have progressed on androgen ablation therapy and are classified into 1 of 3 separate categories:

    • Never received prior chemotherapy/cytotoxic therapy
    • Received prior taxane-based regimen
    • Received 2 prior cytotoxic chemotherapy regimens (including, but not limited to, prior taxane and anthracyclines)

Secondary

  • Determine measurable disease response in patients with measurable disease treated with this drug and overall response rate.
  • Determine the toxic effects of this drug in these patients.
  • Determine the duration of PSA and measurable disease response in patients treated with this drug.
  • Determine the expression of p53, multidrug resistance protein, and Bcl-2 by immunohistochemistry in the primary tumors of patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (none vs 1 prior taxane-containing regimen vs 2 prior cytotoxic regimens).

Patients receive ixabepilone intravenously (IV) over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

ACTUAL ACCRUAL: A total of 124 patients (39 for the no prior chemotherapy stratum; 49 for the prior taxane stratum; 36 for the 2 prior cytotoxic chemotherapy regimens) were accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate

  • Evidence of progressive metastatic disease OR metastatic disease and rising PSA within 4 weeks prior to registration

    • Patients with bone metastases only (i.e., lacking soft tissue disease) must have a PSA level > 10 ng/mL within a week of registration
    • Patients with soft tissue metastasis and/or visceral disease must have measurable disease OR a PSA level > 10 ng/mL within a week prior to registration
    • Patients with stable metastatic disease and rising PSA must show 2 consecutive rises in PSA measurements taken at least 2 weeks apart; most recent PSA level must be obtained within 4 weeks of registration

  • Failed prior bilateral orchiectomy or other primary hormonal therapy

    • Patients who have not undergone bilateral orchiectomy must continue on luteinizing hormone-releasing hormone (LHRH) agonist therapy (e.g., leuprolide or goserelin) or LHRH antagonist (e.g., abarelix) during study treatment
    • Patients without an orchiectomy must have a serum testosterone level < 50 ng/dL within 4 weeks of registration to confirm androgen suppression
  • No carcinomatous meningitis or brain metastases
  • At least 4 weeks since prior flutamide AND continued evidence of progressive disease
  • At least 6 weeks since prior bicalutamide or nilutamide AND continued evidence of progressive disease
  • Depending on the strata, no more than 2 prior cytotoxic chemotherapy regimens for hormone-refractory disease with a taxane-based regimen, mitoxantrone, or another cytotoxic chemotherapy regimen provided there is evidence of progressive disease
  • Up to 1 prior experimental (non-cytotoxic) therapy AND evidence of progressive disease
  • Concurrent bisphosphonates (e.g., pamidronate or zoledronate) allowed provided treatment was initiated at least 4 weeks ago and there is evidence of progressive disease
  • At least 4 weeks since prior estrogen or estrogen-like agents, or other hormonal therapy AND disease progression needs to be confirmed by a rising PSA after the required 4-week washout period
  • Adequate bone marrow function
  • Serum glutamic-pyruvic transaminase (SGPT) < 2 times the institutional upper limit of normal
  • Bilirubin < 1.5 mg/dL
  • Creatinine < 1.5 mg/dL OR a calculated creatinine clearance ≥ 50 mL/min
  • Normal international normalized ratio (INR)
  • Patients must have electrocardiography (ECG) within 4 weeks of registration
  • Patients with a history of prior malignancy are eligible provided they have been treated with curative intent and free of disease for > 5 years (excluding non-melanomatous skin cancers treated with curative intent)
  • Fertile patients must use effective contraception
  • All sites of disease must have been evaluated within 4 weeks of registration
  • Age 18 or older
  • ECOG performance status (PS) of 0-2

Exclusion Criteria:

  • Prior radiotherapy < 4 weeks prior to registration
  • Prior Strontium 89, Samarium 153, or other radioisotope
  • Concurrent estrogen or estrogen-like agents or any other hormonal therapy
  • Active angina pectoris
  • New York Heart Association class III-IV heart disease
  • Myocardial infarction within 6 months prior to registration
  • Evidence of ventricular dysrhythmias or unstable arrhythmia
  • Carcinomatous meningitis or brain metastases.
  • Peripheral neuropathy > grade 1
  • Serious medical illness or active infection that would preclude study participation
  • Concurrent investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00087139

  Show 175 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Study Chair: Glenn Liu, MD University of Wisconsin, Madison
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications:
Wilding G, Chen Y, DiPaola RP, et al.: E3803: Updated results on phase II study of a weekly schedule of BMS-247550 for patients with castrate refractory prostate cancer (CRPC). [Abstract] J Clin Oncol 26 (Suppl 15): A-5070, 2008.
Liu G, Wang W, DiPaola R, et al.: A phase II study of a weekly schedule of BMS-247550 for patients with hormone-refractory prostate cancer: a trial of the Eastern Cooperative Oncology Group (E3803). [Abstract] J Clin Oncol 24 (Suppl 18): A-4618, 2006.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00087139     History of Changes
Other Study ID Numbers: NCI-2009-00548, U10CA021115, E3803, CDR0000372946
Study First Received: July 8, 2004
Results First Received: November 25, 2012
Last Updated: January 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the prostate
recurrent prostate cancer
metastatic prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Epothilones
 Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2013