Ixabepilone in Treating Patients With Metastatic Prostate Cancer

Adenocarcinoma of the Prostate Clinical Trial

Official title:

Phase II Study of a Weekly Schedule of BMS-247550 for Patients With Hormone Refractory Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00087139
• Other study ID #: NCI-2009-00548
• Secondary ID: NCI-2009-00548CD
• Status: Completed
• Phase: Phase 2
• First received: July 8, 2004
• Last updated: April 21, 2014
• Start date: September 2004
• Est. completion date: February 2011

Study information

• Verified date: April 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: February 2011
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Prostate
• Prostatic Neoplasms
• Recurrent Prostate Cancer
• Stage IV Prostate Cancer

Intervention

Drug:
• ixabepilone
Given IV

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With PSA Response	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.	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	No
Secondary	Proportion of Patients With Measurable Disease Response (Best Overall Response)	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	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	No
Secondary	Duration of PSA Response	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.	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	No
Secondary	Duration of Measurable Disease Response	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.	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	No