Hormone Therapy Plus Chemotherapy in Treating Patients With Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Eastern Cooperative Oncology Group
Cancer and Leukemia Group B
Southwest Oncology Group
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00030654
First received: February 14, 2002
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as luteinizing hormone-releasing hormone agonist, flutamide, and bicalutamide may stop the adrenal glands from producing androgens. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining hormone therapy with chemotherapy may kill more tumor cells. It is not yet known whether chemotherapy given at the same time as hormone therapy is more effective than chemotherapy given after hormone therapy in treating prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy given at the same time as hormone therapy with that of chemotherapy given after hormone therapy in treating patients who have prostate cancer.


Condition Intervention Phase
Prostate Cancer
Drug: bicalutamide
Drug: docetaxel
Drug: doxorubicin hydrochloride
Drug: estramustine phosphate sodium
Drug: flutamide
Drug: ketoconazole
Drug: paclitaxel
Drug: releasing hormone agonist therapy
Drug: vinblastine sulfate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized Study of Patients With High Risk, Hormone-Naive Prostate Cancer: Androgen Blockade With 4 Cycles of Immediate Chemotherapy Versus Androgen Blockade With Delayed Chemotherapy

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From date of randomization to the date of death due to any cause ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Biochemical control [ Time Frame: From date of randomization to the date of first PSA failure defined as a PSA doubling time <= 32 weeks ] [ Designated as safety issue: No ]
  • Time to Clinical Failure [ Time Frame: Time from study entry to positive scan or positive disease evaluation of the pelvis or chest or a PSA doubling time ≤ 32 weeks ] [ Designated as safety issue: No ]
  • Frequency of non-hematologic (>= grade 3), hematologic (grade >=4) and fatal (grade 5) toxicities [ Time Frame: From the beginning of treatment to 90 days post treatment ] [ Designated as safety issue: Yes ]

Enrollment: 21
Study Start Date: October 2002
Primary Completion Date: February 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Androgen blockade + immediate chemotherapy
Androgen blockade with immediate chemotherapy
Drug: bicalutamide Drug: docetaxel Drug: doxorubicin hydrochloride Drug: estramustine phosphate sodium Drug: flutamide Drug: ketoconazole Drug: paclitaxel Drug: releasing hormone agonist therapy Drug: vinblastine sulfate
Experimental: Androgen blockade + delayed chemotherapy
Androgen blockade with delayed chemotherapy
Drug: bicalutamide Drug: docetaxel Drug: doxorubicin hydrochloride Drug: estramustine phosphate sodium Drug: flutamide Drug: ketoconazole Drug: paclitaxel Drug: releasing hormone agonist therapy Drug: vinblastine sulfate

Detailed Description:

OBJECTIVES:

Primary

  • Compare the survival of patients with high-risk hormone-naive prostate cancer treated with androgen blockade with concurrent chemotherapy vs delayed chemotherapy.

Secondary

  • Compare biochemical control in patients treated with these regimens.
  • Determine the toxicity of these regimens in these patients.
  • Compare the time to clinical failure, as measured by progression on bone scan or CT scan or a prostate-specific antigen doubling time of ≤ 32 weeks, in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior therapy (surgery vs radiotherapy and/or brachytherapy vs both), original combined Gleason score (6 vs 7 vs 8-10), and prior vaccine therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive androgen blockade (AB) comprising a luteinizing-hormone releasing-hormone agonist continuously and oral flutamide or oral bicalutamide once daily for at least 1 month. Within 4 weeks of initiation of AB, patients begin chemotherapy. Patients receive 1, and only 1, of the following chemotherapy regimens:

    • Regimen A: Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV on day 3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
    • Regimen B: Patients receive oral estramustine 3 times daily on days 1-5 and paclitaxel IV on days 3, 10, 17, 24, 31, and 38. Treatment repeats every 56 days for 4 courses in the absence of disease progression or unacceptable toxicity.
    • Regimen C: Patients receive oral ketoconazole 3 times daily on days 1-7, 15-21, and 29-35; doxorubicin IV on days 1, 15, and 29; vinblastine IV on days 8, 22, and 36; and oral estramustine 3 times daily on days 8-14, 22-28, and 36-42. Treatment repeats every 56 days for 4 courses in the absence of disease progression or unacceptable toxicity.
    • Regimen D: Patients receive oral estramustine 3 times daily on days 1-4 and docetaxel IV over 1 hour on days 3, 10, and 17. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
    • Regimen E: Patients receive docetaxel IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
    • Regimen F: Patients receive docetaxel IV on days 1, 8, and 15. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
    • Regimen G: With approval from the protocol chair, patients may receive a regimen that has been demonstrated in a published phase II study to have at least a 50% response rate as measured by PSA decrease from baseline over 2 measurements 28 days apart or a decrease in measurable soft tissue disease by 50% in 2 dimensions.
  • Arm II: Patients receive AB as in arm I. Patients continue with AB until clinical failure, at which time patients receive chemotherapy as in arm I. Patients who have a response may continue to receive chemotherapy beyond 4 courses.

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

PROJECTED ACCRUAL: A total of 1,050 patients will be accrued for this study within 4-6 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of adenocarcinoma of the prostate

    • Failed local treatments (surgery and/or radiotherapy and/or brachytherapy) as defined by a rising prostate-specific antigen level of at least 2.0 ng/mL (confirmed by 2 measurements at least 2 weeks apart) and a doubling time of 32 weeks or less
    • No clinical or radiographic evidence of disease
    • Original Gleason score of at least 7 OR Gleason score of 6 with capsular penetration or positive seminal vesicles or lymph nodes
  • No metastases

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Zubrod 0-1

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 10 g/dL
  • No history of bleeding disorders that would contraindicate warfarin, including clotting factor defects

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • AST/ALT no greater than 1.5 times upper limit of normal

Renal:

  • Creatinine no greater than 1.5 mg/dL
  • BUN no greater than 1.2 times normal

Cardiovascular:

  • No symptomatic heart disease
  • No history of myocardial infarction
  • No history of thromboembolic events (e.g., deep vein thrombosis, symptomatic cerebrovascular events, or pulmonary embolism)

Other:

  • No other major medical or psychiatric illness that would preclude study entry
  • No other prior or concurrent invasive malignancy within the past 5 years except superficial skin cancer
  • No history of esophageal varices
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 6 weeks since prior vaccine therapy

Chemotherapy:

  • At least 5 years since prior chemotherapy

Endocrine therapy:

  • Prior adjuvant or neoadjuvant hormonal therapy of less than 8 months duration allowed
  • At least 1 year since prior androgen therapy

Radiotherapy:

  • See Disease Characteristics
  • At least 5 years since prior radiotherapy to sites other than prostate

Surgery:

  • See Disease Characteristics

Other:

  • Concurrent warfarin allowed
  • Concurrent bisphosphonate therapy initiated prior to or after randomization allowed
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00030654

  Hide Study Locations
Locations
United States, Arizona
Foundation for Cancer Research and Education
Phoenix, Arizona, United States, 85013
Veterans Affairs Medical Center - Tucson
Tucson, Arizona, United States, 85723
United States, Arkansas
Veterans Affairs Medical Center - Little Rock
Little Rock, Arkansas, United States, 72205
United States, California
Veterans Affairs Outpatient Clinic - Martinez
Martinez, California, United States, 94553
United States, Colorado
Medical Center of Aurora - South Campus
Aurora, Colorado, United States, 80012-0000
Boulder Community Hospital
Boulder, Colorado, United States, 80301-9019
Penrose Cancer Center at Penrose Hospital
Colorado Springs, Colorado, United States, 80933
Memorial Hospital Cancer Center
Colorado Springs, Colorado, United States, 80909
St. Joseph Hospital
Denver, Colorado, United States, 80218-1191
Rocky Mountain Cancer Centers - Denver Rose
Denver, Colorado, United States, 80220
Porter Adventist Hospital
Denver, Colorado, United States, 80210
CCOP - Colorado Cancer Research Program, Incorporated
Denver, Colorado, United States, 80224
Presbyterian - St. Luke's Medical Center
Denver, Colorado, United States, 80218
Swedish Medical Center
Englewood, Colorado, United States, 80112
Sky Ridge Medical Center
Lone Tree, Colorado, United States, 80124
Hope Cancer Care Center at Longmont United Hospital
Longmont, Colorado, United States, 80501
St. Mary-Corwin Regional Medical Center
Pueblo, Colorado, United States, 81004
Rocky Mountain Cancer Centers - Thornton
Thornton, Colorado, United States, 80221
United States, Florida
Shands Cancer Center at the University of Florida Health Science Center
Gainesville, Florida, United States, 32610-0385
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Gulf Coast Cancer Treatment Center
Panama City, Florida, United States, 32405-4587
Tallahassee Memorial Hospital
Tallahassee, Florida, United States, 32308
Veterans Affairs Medical Center - Tampa (Haley)
Tampa, Florida, United States, 33612
United States, Idaho
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
Boise, Idaho, United States, 83706
United States, Illinois
Veterans Affairs Medical Center - Hines
Hines, Illinois, United States, 60141
United States, Iowa
John Stoddard Cancer Center at Iowa Lutheran Hospital
Des Moines, Iowa, United States, 50316-2301
John Stoddard Cancer Center at Iowa Methodist Medical Center
Des Moines, Iowa, United States, 50309
Mercy Cancer Center at Mercy Medical Center - Des Moines
Des Moines, Iowa, United States, 50314
Wendt Regional Cancer Center at Finley Hospital
Dubuque, Iowa, United States, 52001
United States, Kansas
Veterans Affairs Medical Center - Wichita
Wichita, Kansas, United States, 67218
United States, Kentucky
Veterans Affairs Medical Center - Lexington
Lexington, Kentucky, United States, 40502-2236
United States, Louisiana
Veterans Affairs Medical Center - New Orleans
New Orleans, Louisiana, United States, 70112
Veterans Affairs Medical Center - Shreveport
Shreveport, Louisiana, United States, 71101-4295
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0010
Veterans Affairs Medical Center - Detroit
Detroit, Michigan, United States, 48201-1932
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007
United States, Mississippi
Veterans Affairs Medical Center - Jackson
Jackson, Mississippi, United States, 39216
United States, Missouri
Cancer Research for the Ozarks
Springfield, Missouri, United States, 65807
United States, Nebraska
Midlands Cancer Center at Midlands Community Hospital
Papillion, Nebraska, United States, 68128-4157
United States, New Mexico
MBCCOP - University of New Mexico HSC
Albuquerque, New Mexico, United States, 87131
Veterans Affairs Medical Center - Albuquerque
Albuquerque, New Mexico, United States, 87108-5138
United States, New York
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, United States, 10016
Lipson Cancer and Blood Center at Rochester General Hospital
Rochester, New York, United States, 14621
United States, North Carolina
CCOP - Southeast Cancer Control Consortium
Goldsboro, North Carolina, United States, 27534-9479
United States, Ohio
Akron General's McDowell Cancer Center
Akron, Ohio, United States, 44302
Akron City Hospital at Summa Health System
Akron, Ohio, United States, 44304
Veterans Affairs Medical Center - Cincinnati
Cincinnati, Ohio, United States, 45220-2288
Veterans Affairs Medical Center - Dayton
Dayton, Ohio, United States, 45428-1002
Cancer Care Center, Incorporated
Salem, Ohio, United States, 44460
Cancer Treatment Center
Wooster, Ohio, United States, 44691
United States, Oregon
Veterans Affairs Medical Center - Portland
Portland, Oregon, United States, 97207
United States, Pennsylvania
Mercy Fitzgerald Hospital
Darby, Pennsylvania, United States, 19023
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Mercy Hospital Cancer Center - Scranton
Scranton, Pennsylvania, United States, 18501
United States, South Carolina
Veterans Affairs Medical Center - Charleston
Charleston, South Carolina, United States, 29401-5799
CCOP - Greenville
Greenville, South Carolina, United States, 29615
United States, South Dakota
Rapid City Regional Hospital
Rapid City, South Dakota, United States, 57709
United States, Tennessee
Erlanger Cancer Center
Chattanooga, Tennessee, United States, 37403
Veterans Affairs Medical Center - Memphis
Memphis, Tennessee, United States, 38104
Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
Nashville, Tennessee, United States, 37232-5671
United States, Texas
Veterans Affairs Medical Center - Amarillo
Amarillo, Texas, United States, 79106
University of Texas Medical Branch
Galveston, Texas, United States, 77555-0209
Veterans Affairs Medical Center - San Antonio (Murphy)
San Antonio, Texas, United States, 78229
Veterans Affairs Medical Center - Temple
Temple, Texas, United States, 76504
United States, Utah
Cottonwood Hospital Medical Center
Murray, Utah, United States, 84107
McKay-Dee Hospital Center
Ogden, Utah, United States, 84403
Utah Valley Regional Medical Center - Provo
Provo, Utah, United States, 84604
Dixie Regional Medical Center
Saint George, Utah, United States, 84770
Veterans Affairs Medical Center - Salt Lake City
Salt Lake City, Utah, United States, 84148
United States, Washington
Veterans Affairs Medical Center - Seattle
Seattle, Washington, United States, 98108
United States, Wisconsin
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, United States, 54301
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449
All Saints Cancer Center at All Saints Healthcare
Racine, Wisconsin, United States, 53405
Australia, New South Wales
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Peru
Instituto de Enfermedades Neoplasicas
Lima, Peru, 34
Puerto Rico
San Juan City Hospital
San Juan, Puerto Rico, 00936-7344
Sponsors and Collaborators
Radiation Therapy Oncology Group
Eastern Cooperative Oncology Group
Cancer and Leukemia Group B
Southwest Oncology Group
Investigators
Study Chair: Kenneth J. Pienta, MD, FACP University of Michigan Cancer Center
Study Chair: Naomi S. Balzer-Haas, MD Fox Chase Cancer Center
Study Chair: Arif Hussain, MD University of Maryland Greenebaum Cancer Center
Study Chair: Gregory P. Swanson, MD Deaconess Medical Center, Spokane, Washington
Study Chair: Primo N. Lara, MD University of California, Davis
  More Information

Additional Information:
Publications:
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00030654     History of Changes
Other Study ID Numbers: RTOG-P-0014, CDR0000069186, RTOG-DEV-1028, ECOG-RTOG-P-0014, CALGB-RTOG-P-0014, SWOG-RTOG-P-0014
Study First Received: February 14, 2002
Last Updated: November 12, 2013
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
adenocarcinoma of the prostate
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IV prostate cancer
recurrent prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Hormones
Bicalutamide
Liposomal doxorubicin
Doxorubicin
Estramustine
Vinblastine
Androgens
Ketoconazole
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Androgen Antagonists
Hormone Antagonists
Antineoplastic Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on September 30, 2014