Ixabepilone in Treating Patients With Metastatic Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00087139
First received: July 8, 2004
Last updated: April 21, 2014
Last verified: April 2013
  Purpose

Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop tumor cells from dividing so they stop growing or die. 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
Adenocarcinoma of the Prostate
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Drug: ixabepilone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: 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:


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.

    Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.

    Objective response = CR + PR


  • 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
Study Completion Date: February 2011
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I

Patients are stratified according to prior chemotherapy (none vs 1 prior taxane-containing regimen vs 2 prior cytotoxic regimens).

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

Drug: ixabepilone
Given IV
Other Names:
  • BMS-247550
  • epothilone B lactam
  • Ixempra

Detailed Description:

PRIMARY OBJECTIVE:

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

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

SECONDARY OBJECTIVES:

I. Determine measurable disease response in patients with measurable disease treated with this drug and overall response rate.

II. Determine the toxic effects of this drug in these patients. III. Determine the duration of PSA and measurable disease response in patients treated with this drug.

IV. 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 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.

  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
  • Metastatic disease
  • Evidence of disease progression (e.g., new lesions on bone scan or new/enlarging lesions on CT scan) OR rising prostate-specific antigen (PSA) within the past 4 weeks
  • Radiologic evidence of hydronephrosis alone is not considered evidence of metastatic disease (e.g., increasing PSA)
  • Patients with bone metastases only (i.e., lacking soft tissue disease) must have a PSA level >= 10 ng/mL within the past week
  • Patients with stable 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 the past 4 weeks
  • Disease progression after prior anti-androgen withdrawal must be confirmed by a rising PSA after the 4-6 week washout period (e.g., PSA level higher than the last PSA obtained while on anti-androgen therapy)
  • 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 AND must have a serum testosterone level =< 50 ng/dL within the past 4 weeks to confirm androgen suppression
  • ECOG 0-2
  • Granulocyte count >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • WBC >= 4,000/mm^3
  • SGPT =< 2 times upper limit of normal
  • Bilirubin =< 1.5 mg/dL
  • INR normal
  • Creatinine =< 1.5 mg/dL
  • Creatinine clearance >= 50 mL/min
  • No New York Heart Association class III-IV heart disease
  • No myocardial infarction within the past 6 months
  • No active angina pectoris
  • No evidence of ventricular dysrhythmias or other unstable arrhythmia
  • Rate-controlled atrial fibrillation allowed provided the patient is asymptomatic
  • No other malignancy within the past 5 years except curatively treated nonmelanoma skin cancer
  • No serious medical illness or active infection that would preclude study participation
  • No concurrent prophylactic filgrastim (G-CSF)
  • No more than 2 prior cytotoxic chemotherapy regimens for hormone-refractory disease
  • At least 4 weeks since prior chemotherapy with a taxane-based regimen, mixantrone, or another cytotoxic chemotherapy regimen provided there is evidence of progressive disease
  • 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
  • At least 4 weeks since prior estrogen or estrogen-like agents (e.g., PC-SPES, saw palmetto, or other herbal products which may contain phytoestrogens)
  • At least 4 weeks since prior hormonal therapy, including megestrol, finasteride, ketoconazole, or systemic corticosteroids
  • No concurrent estrogen or estrogen-like agents (e.g., PC-SPES, saw palmetto, or other herbal products which may contain phytoestrogens)
  • More than 4 weeks since prior radiotherapy
  • No prior strontium chloride Sr 89 or samarium Sm 153 lexidronam pentasodium
  • No other prior radioisotope
  • No concurrent radiotherapy for pain control
  • No more than 1 prior experimental (non-cytotoxic) therapy AND evidence of progressive disease
  • At least 4 weeks since prior experimental therapy
  • Concurrent bisphosphonates (e.g., pamidronate or zoledronate) allowed provided treatment was initiated at least 4 weeks ago and there is evidence of progressive disease
  • No other concurrent investigational agents
  • No concurrent therapeutic warfarin
  • Concurrent prophylactic or therapeutic doses of low molecular weight heparin allowed provided criterion for INR is met
  • No carcinomatous meningitis or brain metastases
  • Fertile patients must use effective contraception
  • No peripheral neuropathy > grade 1
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00087139

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Sponsors and Collaborators
Investigators
Principal Investigator: Glenn Liu Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00087139     History of Changes
Other Study ID Numbers: NCI-2009-00548, NCI-2009-00548, CDR0000372946, E3803, E3803, E3803, U10CA021115
Study First Received: July 8, 2004
Results First Received: November 25, 2012
Last Updated: April 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Epothilone B
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014