Ixabepilone in Treating Patients With Metastatic Prostate Cancer

Phase 2

Completed

Conditions: Adenocarcinoma of the Prostate
Recurrent Prostate Cancer
Stage IV Prostate Cancer

Interventions: Drug: ixabepilone

Registration Number: NCT00087139

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 124

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	ixabepilone	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.

Primary Outcome Measures

Name	Time	Method
Proportion of Patients With PSA Response	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	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

Name	Time	Method
Proportion of Patients With Measurable Disease Response (Best Overall Response)	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	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	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	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	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	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.

Trial Locations

Locations (162): Elkhart General Hospital
🇺🇸
Elkhart, Indiana, United States
Saint Luke's Regional Medical Center
🇺🇸
Sioux City, Iowa, United States
Methodist Medical Center of Illinois
🇺🇸
Peoria, Illinois, United States
Garneau, Stewart C MD (UIA Investigator)
🇺🇸
Moline, Illinois, United States
Hopedale Medical Complex - Hospital
🇺🇸
Hopedale, Illinois, United States
Saint Mary Corwin Medical Center
🇺🇸
Pueblo, Colorado, United States
Rush - Copley Medical Center
🇺🇸
Aurora, Illinois, United States
Illinois CancerCare Galesburg
🇺🇸
Galesburg, Illinois, United States
Exempla Lutheran Medical Center
🇺🇸
Wheat Ridge, Colorado, United States
Stoffel, Thomas J MD (UIA Investigator)
🇺🇸
Moline, Illinois, United States
Mcdonough District Hospital
🇺🇸
Macomb, Illinois, United States
Eureka Hospital
🇺🇸
Eureka, Illinois, United States
Boulder Community Hospital
🇺🇸
Boulder, Colorado, United States
Saint Anthony Hospital
🇺🇸
Lakewood, Colorado, United States
McKee Medical Center
🇺🇸
Loveland, Colorado, United States
Lakeland Regional Cancer Center
🇺🇸
Lakeland, Florida, United States
Kewanee Hospital
🇺🇸
Kewanee, Illinois, United States
Memorial Hospital
🇺🇸
Carthage, Illinois, United States
Galesburg Cottage Hospital
🇺🇸
Galesburg, Illinois, United States
Pekin Hospital
🇺🇸
Pekin, Illinois, United States
Nanticoke Memorial Hospital
🇺🇸
Seaford, Delaware, United States
Mason District Hospital
🇺🇸
Havana, Illinois, United States
Saint Francis Hospital - Wilmington
🇺🇸
Wilmington, Delaware, United States
North Colorado Medical Center
🇺🇸
Greeley, Colorado, United States
Advocate Sherman Hospital
🇺🇸
Elgin, Illinois, United States
Alexian Brothers Medical and Cancer Center
🇺🇸
Elk Grove Village, Illinois, United States
Joliet Oncology-Hematology Associates Limited
🇺🇸
Joliet, Illinois, United States
Penrose-Saint Francis Healthcare
🇺🇸
Colorado Springs, Colorado, United States
MetroHealth Medical Center
🇺🇸
Cleveland, Ohio, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸
Denver, Colorado, United States
Rose Medical Center
🇺🇸
Denver, Colorado, United States
Colorado Cancer Research Program CCOP
🇺🇸
Denver, Colorado, United States
Porter Adventist Hospital
🇺🇸
Denver, Colorado, United States
Exempla Saint Joseph Hospital
🇺🇸
Denver, Colorado, United States
Saint John Hospital and Medical Center
🇺🇸
Detroit, Michigan, United States
Longmont United Hospital
🇺🇸
Longmont, Colorado, United States
Sky Ridge Medical Center
🇺🇸
Lone Tree, Colorado, United States
North Suburban Medical Center
🇺🇸
Thornton, Colorado, United States
Graham Hospital Association
🇺🇸
Canton, Illinois, United States
Porubcin, Michael MD (UIA Investigator)
🇺🇸
Moline, Illinois, United States
Sharis, Christine M MD (UIA Investigator)
🇺🇸
Moline, Illinois, United States
Community Cancer Center Foundation
🇺🇸
Normal, Illinois, United States
Pekin Cancer Treatment Center
🇺🇸
Pekin, Illinois, United States
Cedar Rapids Oncology Association
🇺🇸
Cedar Rapids, Iowa, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸
Ottawa, Illinois, United States
Saint Mary's Hospital and Regional Medical Center
🇺🇸
Grand Junction, Colorado, United States
Edna Williams Cancer Center at the Baptist Cancer Institute
🇺🇸
Jacksonville, Florida, United States
Vigliotti, Antonio, P.G. M.D. (UIA Investigator)
🇺🇸
Moline, Illinois, United States
Bromenn Regional Medical Center
🇺🇸
Normal, Illinois, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸
Ottawa, Illinois, United States
Proctor Hospital
🇺🇸
Peoria, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸
Peoria, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸
Peoria, Illinois, United States
Perry Memorial Hospital
🇺🇸
Princeton, Illinois, United States
Illinois Oncology Research Association CCOP
🇺🇸
Peoria, Illinois, United States
Illinois Valley Hospital
🇺🇸
Peru, Illinois, United States
Saint Margaret's Hospital
🇺🇸
Spring Valley, Illinois, United States
Memorial Medical Center
🇺🇸
Springfield, Illinois, United States
Carle Clinic-Urbana Main
🇺🇸
Urbana, Illinois, United States
Community Howard Regional Health
🇺🇸
Kokomo, Indiana, United States
Saint Joseph Regional Medical Center - Mishawaka
🇺🇸
Plymouth, Indiana, United States
Memorial Hospital of South Bend
🇺🇸
South Bend, Indiana, United States
Indiana University Health La Porte Hospital
🇺🇸
La Porte, Indiana, United States
Franciscan Saint Anthony Health-Michigan City
🇺🇸
Michigan City, Indiana, United States
Saint Joseph Regional Medical Center-Mishawaka
🇺🇸
Mishawaka, Indiana, United States
Northern Indiana Cancer Research Consortium
🇺🇸
South Bend, Indiana, United States
South Bend Clinic
🇺🇸
South Bend, Indiana, United States
McFarland Clinic PC-William R Bliss Cancer Center
🇺🇸
Ames, Iowa, United States
Mercy Hospital
🇺🇸
Cedar Rapids, Iowa, United States
Constantinou, Costas L MD (UIA Investigator)
🇺🇸
Bettendorf, Iowa, United States
Saint Luke's Hospital
🇺🇸
Cedar Rapids, Iowa, United States
Saint Anthony Regional Hospital
🇺🇸
Carroll, Iowa, United States
Medical Oncology and Hematology Associates-West Des Moines
🇺🇸
Clive, Iowa, United States
Alegent Health Mercy Hospital
🇺🇸
Council Bluffs, Iowa, United States
Community Memorial Hospital
🇺🇸
Missouri Valley, Iowa, United States
Burgess Memorial Hospital
🇺🇸
Onawa, Iowa, United States
Siouxland Regional Cancer Center
🇺🇸
Sioux City, Iowa, United States
Siouxland Hematology Oncology Associates
🇺🇸
Sioux City, Iowa, United States
Mercy Medical Center-Sioux City
🇺🇸
Sioux City, Iowa, United States
Greater Baltimore Medical Center
🇺🇸
Baltimore, Maryland, United States
Eastern Cooperative Oncology Group
🇺🇸
Boston, Massachusetts, United States
Morton Hospital and Medical Center
🇺🇸
Taunton, Massachusetts, United States
Oakwood Hospital
🇺🇸
Dearborn, Michigan, United States
Green Bay Oncology - Escanaba
🇺🇸
Escanaba, Michigan, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Genesys Regional Medical Center-West Flint Campus
🇺🇸
Flint, Michigan, United States
Green Bay Oncology - Iron Mountain
🇺🇸
Iron Mountain, Michigan, United States
Allegiance Health
🇺🇸
Jackson, Michigan, United States
Sparrow Hospital
🇺🇸
Lansing, Michigan, United States
Kalamazoo Center for Medical Studies
🇺🇸
Kalamazoo, Michigan, United States
Saint Joseph Mercy Oakland
🇺🇸
Pontiac, Michigan, United States
Saint Mary's of Michigan
🇺🇸
Saginaw, Michigan, United States
Saint Joseph Mercy Port Huron
🇺🇸
Port Huron, Michigan, United States
Lakeland Hospital
🇺🇸
St. Joseph, Michigan, United States
Essentia Health Duluth Clinic CCOP
🇺🇸
Duluth, Minnesota, United States
Essentia Health Saint Mary's Medical Center
🇺🇸
Duluth, Minnesota, United States
Miller-Dwan Hospital
🇺🇸
Duluth, Minnesota, United States
Meeker County Memorial Hospital
🇺🇸
Litchfield, Minnesota, United States
Virginia Piper Cancer Institute
🇺🇸
Minneapolis, Minnesota, United States
Saint Joseph's Hospital - Healtheast
🇺🇸
Saint Paul, Minnesota, United States
Bryan LGH Medical Center West
🇺🇸
Lincoln, Nebraska, United States
Woodwinds Health Campus
🇺🇸
Woodbury, Minnesota, United States
Fremont Area Medical Center
🇺🇸
Fremont, Nebraska, United States
Midlands Community Hospital
🇺🇸
Papillion, Nebraska, United States
Bryan LGH Medical Center East
🇺🇸
Lincoln, Nebraska, United States
Cancer Institute of New Jersey At Hamilton
🇺🇸
Hamilton, New Jersey, United States
Saint Elizabeth Regional Medical Center
🇺🇸
Lincoln, Nebraska, United States
Ocean Medical Center
🇺🇸
Brick, New Jersey, United States
Hunterdon Medical Center
🇺🇸
Flemington, New Jersey, United States
Morristown Memorial Hospital
🇺🇸
Morristown, New Jersey, United States
Mountainside Hospital
🇺🇸
Montclair, New Jersey, United States
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
🇺🇸
Mount Holly, New Jersey, United States
Virtua West Jersey Hospital Voorhees
🇺🇸
Voorhees, New Jersey, United States
Overlook Hospital
🇺🇸
Summit, New Jersey, United States
Mary Imogene Bassett Hospital
🇺🇸
Cooperstown, New York, United States
Lehigh Valley Hospital
🇺🇸
Allentown, Pennsylvania, United States
Bryn Mawr Hospital
🇺🇸
Bryn Mawr, Pennsylvania, United States
Saint Luke's University Hospital-Bethlehem Campus
🇺🇸
Bethlehem, Pennsylvania, United States
Penn State Milton S Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
Lewistown Hospital
🇺🇸
Lewistown, Pennsylvania, United States
Mount Nittany Medical Center
🇺🇸
State College, Pennsylvania, United States
Paoli Memorial Hospital
🇺🇸
Paoli, Pennsylvania, United States
Sanford Cancer Center-Oncology Clinic
🇺🇸
Sioux Falls, South Dakota, United States
Medical X-Ray Center
🇺🇸
Sioux Falls, South Dakota, United States
Mainline Health CCOP
🇺🇸
Wynnewood, Pennsylvania, United States
Lankenau Hospital
🇺🇸
Wynnewood, Pennsylvania, United States
Sanford USD Medical Center - Sioux Falls
🇺🇸
Sioux Falls, South Dakota, United States
Sacred Heart Hospital
🇺🇸
Eau Claire, Wisconsin, United States
Green Bay Oncology at Saint Vincent Hospital
🇺🇸
Green Bay, Wisconsin, United States
Saint Vincent Hospital
🇺🇸
Green Bay, Wisconsin, United States
Green Bay Oncology Limited at Saint Mary's Hospital
🇺🇸
Green Bay, Wisconsin, United States
Saint Mary's Hospital
🇺🇸
Green Bay, Wisconsin, United States
Gundersen Lutheran
🇺🇸
La Crosse, Wisconsin, United States
Bay Area Medical Center
🇺🇸
Marinette, Wisconsin, United States
Green Bay Oncology - Oconto Falls
🇺🇸
Oconto Falls, Wisconsin, United States
Marshfield Clinic-Rice Lake Center
🇺🇸
Rice Lake, Wisconsin, United States
Marshfield Clinic - Weston Center
🇺🇸
Weston, Wisconsin, United States
Green Bay Oncology - Sturgeon Bay
🇺🇸
Sturgeon Bay, Wisconsin, United States
Oncology Associates at Mercy Medical Center
🇺🇸
Cedar Rapids, Iowa, United States
Saint John Macomb-Oakland Hospital
🇺🇸
Warren, Michigan, United States
Saint Joseph Medical Center
🇺🇸
Bloomington, Illinois, United States
Swedish Medical Center
🇺🇸
Englewood, Colorado, United States
Mercy Medical Center
🇺🇸
Canton, Ohio, United States
Saint Mary Mercy Hospital
🇺🇸
Livonia, Michigan, United States
Cancer Institute of New Jersey
🇺🇸
New Brunswick, New Jersey, United States
UW Cancer Center Johnson Creek
🇺🇸
Johnson Creek, Wisconsin, United States
Marshfield Clinic - Wisconsin Rapids Center
🇺🇸
Wisconsin Rapids, Wisconsin, United States
The Medical Center of Aurora
🇺🇸
Aurora, Colorado, United States
Mercy Capitol
🇺🇸
Des Moines, Iowa, United States
Iowa Methodist Medical Center
🇺🇸
Des Moines, Iowa, United States
Iowa Oncology Research Association CCOP
🇺🇸
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Laurel
🇺🇸
Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸
Des Moines, Iowa, United States
Iowa Lutheran Hospital
🇺🇸
Des Moines, Iowa, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
Michigan Cancer Research Consortium Community Clinical Oncology Program
🇺🇸
Ann Arbor, Michigan, United States
Albert Einstein College of Medicine
🇺🇸
Bronx, New York, United States
Montefiore Medical Center-Wakefield Campus
🇺🇸
Bronx, New York, United States
UW Health Oncology - 1 South Park
🇺🇸
Madison, Wisconsin, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States