S0032, Combination Chemotherapy Plus Hormone Therapy in Treating Patients With Metastatic Prostate Cancer

Phase II Evaluation of Early Oral Estramustine, Oral Etoposide and Intravenous Paclitaxel in Combination With Hormone Therapy in Patients With High-Risk Metastatic Adenocarinoma of the Prostate

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Androgens can stimulate the growth of prostate cancer cells. Drugs such as goserelin, leuprolide, flutamide, or bicalutamide may stop the adrenal glands from producing androgens. Combining chemotherapy with hormone therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus hormone therapy in treating patients who have metastatic prostate cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: etoposide; Drug: leuprolide; Drug: paclitaxel; Drug: flutamide; Drug: bicalutamide; Drug: goserelin; Drug: estramustine; Drug: nilutamide

Detailed Description

OBJECTIVES:

• Determine the progression-free and overall survival in patients with high-risk metastatic adenocarcinoma of the prostate treated with early estramustine, etoposide, and paclitaxel with combined androgen-blockade therapy.
• Determine the type, frequency, and severity of toxicity of this regimen in this patient population.

OUTLINE: This is a multicenter study.

• Androgen-blockade therapy: Patients receive a standard regimen of luteinizing hormone-releasing hormone agonist therapy comprising either goserelin subcutaneously once monthly or once every 3 months or leuprolide intramuscularly once monthly, once every 3 months, or once every 4 months. Patients also receive a standard regimen of antiandrogen therapy comprising oral bicalutamide, oral flutamide, or oral nilutamide once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
• Chemotherapy: Beginning 14-30 days after initiation of androgen-blockade therapy, patients receive oral estramustine three times daily and oral etoposide once daily on days 1-14 and paclitaxel IV over 1 hour on day 2. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression, every 6 months for 2 years, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 2 years.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36607
      • MBCCOP - Gulf Coast
  • Arizona
    • Phoenix, Arizona, United States, 85006-2726
      • CCOP - Western Regional, Arizona
    • Phoenix, Arizona, United States, 85012
      • Veterans Affairs Medical Center - Phoenix (Carl T. Hayden)
    • Tucson, Arizona, United States, 85723
      • Veterans Affairs Medical Center - Tucson
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center at University of Arizona Health Sciences Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
    • Little Rock, Arkansas, United States, 72205
      • Veterans Affairs Medical Center - Little Rock
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Los Angeles, California, United States, 90073
      • Veterans Affairs Medical Center - West Los Angeles
    • Martinez, California, United States, 94553
      • Veterans Affairs Outpatient Clinic - Martinez
    • Oakland, California, United States, 94609-3305
      • CCOP - Bay Area Tumor Institute
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Santa Rosa, California, United States, 95403
      • CCOP - Santa Rosa Memorial Hospital
  • Colorado
    • Aurora, Colorado, United States, 80010
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
    • Denver, Colorado, United States, 80220
      • Veterans Affairs Medical Center - Denver
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • MBCCOP - Howard University Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Veterans Affairs Medical Center - Tampa (Haley)
  • Georgia
    • Atlanta, Georgia, United States, 30342-1701
      • CCOP - Atlanta Regional
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • MBCCOP - Hawaii
  • Illinois
    • Chicago, Illinois, United States, 60612
      • MBCCOP - University of Illinois at Chicago
    • Chicago, Illinois, United States, 60612
      • Veterans Affairs Medical Center - Chicago Westside Hospital
    • Decatur, Illinois, United States, 62526
      • CCOP - Central Illinois
    • Hines, Illinois, United States, 60141
      • Veterans Affairs Medical Center - Hines
    • Maywood, Illinois, United States, 60153-5500
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160-7390
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67218
      • Veterans Affairs Medical Center - Wichita
  • Kentucky
    • Lexington, Kentucky, United States, 40502-2236
      • Veterans Affairs Medical Center - Lexington
    • Lexington, Kentucky, United States, 40536-0084
      • Markey Cancer Center at University of Kentucky Chandler Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Veterans Affairs Medical Center - New Orleans
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
    • New Orleans, Louisiana, United States, 70112
      • Tulane Cancer Center at Tulane University Hospital and Clinic
    • Shreveport, Louisiana, United States, 71130-3932
      • Feist-Weiller Cancer Center at Louisiana State University Health Sciences
    • Shreveport, Louisiana, United States, 71101-4295
      • Veterans Affairs Medical Center - Shreveport
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Cancer Research Center at Boston Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Ann Arbor, Michigan, United States, 48109-0946
      • University of Michigan Comprehensive Cancer Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48201-1932
      • Veterans Affairs Medical Center - Detroit
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Health System
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Royal Oak, Michigan, United States, 48073-6769
      • CCOP - Beaumont
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Institute at Providence Hospital - Southfield Campus
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Medical Center
    • Jackson, Mississippi, United States, 39216
      • Veterans Affairs Medical Center - Jackson
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
    • Saint Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center
    • Springfield, Missouri, United States, 65807
      • CCOP - Cancer Research for the Ozarks
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108-5138
      • Veterans Affairs Medical Center - Albuquerque
    • Albuquerque, New Mexico, United States, 87131
      • MBCCOP - University of New Mexico HSC
  • New York
    • Cheektowaga, New York, United States, 14225
      • Western New York Urology Associates
    • New York, New York, United States, 10016
      • NYU Cancer Institute at New York University Medical Center
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534-9479
      • CCOP - Southeast Cancer Control Consortium
  • Ohio
    • Cincinnati, Ohio, United States, 45220-2288
      • Veterans Affairs Medical Center - Cincinnati
    • Cincinnati, Ohio, United States, 45267-0501
      • Charles M. Barrett Cancer Center at University Hospital
    • Cleveland, Ohio, United States, 44195-9001
      • Cleveland Clinic Taussig Cancer Center
    • Columbus, Ohio, United States, 43206
      • CCOP - Columbus
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Dayton, Ohio, United States, 45428-1002
      • Veterans Affairs Medical Center - Dayton
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97201-3098
      • Cancer Institute at Oregon Health and Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Charleston, South Carolina, United States, 29401-5799
      • Veterans Affairs Medical Center - Charleston
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • University of Tennessee Cancer Institute at Methodist Central Hospital
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Tech University Health Sciences Center School of Medicine
    • Amarillo, Texas, United States, 79106
      • Harrington Cancer Center
    • Amarillo, Texas, United States, 79106
      • Veterans Affairs Medical Center - Amarillo
    • Fort Sam Houston, Texas, United States, 78234-6200
      • Brooke Army Medical Center
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030-4095
      • M.D. Anderson Cancer Center at University of Texas
    • Lubbock, Texas, United States, 79415-3364
      • UMC Southwest Cancer and Research Center
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
    • Temple, Texas, United States, 76504
      • Veterans Affairs Medical Center - Temple
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84148
      • Veterans Affairs Medical Center - Salt Lake City
    • Salt Lake City, Utah, United States, 84132
      • Huntsman Cancer Institute at University of Utah
  • Virginia
    • Norfolk, Virginia, United States, 23510-1115
      • Sentara Cancer Institute at Sentara Norfolk General Hospital
  • Washington
    • Seattle, Washington, United States, 98101
      • CCOP - Virginia Mason Research Center
    • Seattle, Washington, United States, 98108
      • Veterans Affairs Medical Center - Seattle
    • Seattle, Washington, United States, 98109
      • Puget Sound Oncology Consortium
    • Tacoma, Washington, United States, 98405-0986
      • CCOP - Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed high-risk adenocarcinoma of the prostate

  • Clinical stage D2 disease as evidenced by one of the following:

    • Visceral disease (liver, lung, or other viscera)
    • Bone metastases to sites in both the axial (spine, pelvis, ribs, or skull) and appendicular (claviculae, humeri, or femora) skeleton

• No prior or concurrent (treated or untreated) brain metastases

  • Patients with clinical evidence of brain metastasis must have a negative brain CT or MRI
• No evidence of untreated spinal cord compression

PATIENT CHARACTERISTICS:

Age:

• Over 18

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No active hypercoagulability

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No transient ischemic attacks, stroke, or myocardial infarction within the past 6 months
• No active coronary artery disease requiring antianginal therapy
• No active thrombophlebitis

Pulmonary:

• No history of pulmonary embolus

Other:

• No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior biologic therapy and recovered
• No concurrent biologic therapy

Chemotherapy:

• No prior cytotoxic chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• Prior androgen-blockade therapy (e.g., luteinizing hormone-releasing hormone agonist and antiandrogen therapy) allowed if administered for a duration of less than 30 days
• Prior neoadjuvant hormonal therapy allowed

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• At least 4 weeks since prior surgery and recovered

Other:

• No concurrent bisphosphonates

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hormone therapy, estramustine, etoposide and paclitaxel; Hormone therapy (leuprolide, bicalutamide, nilutamide, goserelin, flutamide), estramustine, etoposide and paclitaxel	Drug: etoposide; Drug: leuprolide; Other Names: leuprolide acetate; Drug: paclitaxel; Drug: flutamide; Drug: bicalutamide; Drug: goserelin; Drug: estramustine; Other Names: estramustine phosphate sodium; Drug: nilutamide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	Measured from time of registration to time of first documentation of progression determined from the prostate-specific antigen (PSA) level, clinical criteria, or symptomatic deterioration. PSA progression is defined as a 25% increase greater than baseline. If the patient's PSA level had decrease during the study, a 25% increase from the nadir PSA level, with absolute value of >=5 ng/mL is considered progression. CLinical progress is defined as the appearance of any new lesion at any site or death without documented progression. Symptomatic deterioration is defined as a global deterioration of the health status requiring discontinuation of treatment without objective evidence of progression.	0-5 years (assessed every 3 months if no progression when the chemotherapy had been finished. Once off chemotherapy, assessed every 3 months until progression)
Overall Survival (OS)	Overall survival is defined from the date of registration to date of death from any cause	0-5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug	Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.	up to 5 years after registration

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: David C. Smith, MD, University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start: December 1, 2001
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: January 4, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 16, 2013
• Last Update Submitted That Met QC Criteria: June 12, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: stage IV prostate cancer; recurrent prostate cancer; adenocarcinoma of the prostate
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Androgen Antagonists; Etoposide; Paclitaxel; Leuprolide; Goserelin; Bicalutamide; Estramustine; Flutamide; Nilutamide
• Other Study ID Numbers: CDR0000069132; U10CA032102 (U.S. NIH Grant/Contract); S0032 (Other Identifier: SWOG)