Chemotherapy Plus Hormone Therapy Versus Androgen Suppression in Treating Patients With Metastatic or Unresectable Prostate Cancer

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT00002855
Collaborator
National Cancer Institute (NCI) (NIH)
306
1
2
106
2.9

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining hormone therapy with chemotherapy and androgen suppression may kill more tumor cells. It is not yet known which treatment regimen is more effective for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy plus hormone therapy versus androgen suppression alone as initial therapy in patients with prostate cancer that is metastatic or that cannot be removed surgically.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

OBJECTIVES:
  • Determine the clinical benefit, as measured by time to progression and overall survival, of chemo/hormonal therapy compared to androgen ablation alone, when given as the initial systemic treatment in patients with acinar adenocarcinoma of the prostate that is not amenable to local therapy.

  • Validate the clinical significance of PSA criteria for progression.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients are treated with medical or surgical castration followed by an anti-androgen therapy with either flutamide, bicalutamide, or nilutamide.

  • Arm II: Patients receive chemo/hormonal therapy for 3 eight week courses, followed by total androgen blockade. Each course consists of 6 weeks of cytotoxic therapy with doxorubicin, ketoconazole, vinblastine, and estramustine followed by 2 weeks of rest. These patients are also maintained on hydrocortisone both during treatment and during rest.

Patients in arm II have a long-term central venous access device inserted.

PROJECTED ACCRUAL: A total of 368 patients will be accrued for this study.

Study Design

Study Type:
Interventional
Actual Enrollment :
306 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 3 Trial of Androgen Ablation Alone vs. Chemo/Hormonal Therapy as Initial Treatment of Unresectable/Metastatic Adenocarcinoma of the Prostate
Study Start Date :
Aug 1, 1996
Actual Primary Completion Date :
Jun 1, 2005
Actual Study Completion Date :
Jun 1, 2005

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I

Arm I: Medical or surgical castration followed by an anti-androgen therapy with either flutamide, bicalutamide, or nilutamide.

Drug: Bicalutamide
Other Names:
  • Casodex
  • Drug: Flutamide
    Other Names:
  • Eulexin
  • Drug: Nilutamide
    Other Names:
  • Anandron
  • Nilandron
  • Procedure: Conventional Surgery
    Surgical castration
    Other Names:
  • Castration
  • Experimental: Arm II

    Arm II: Chemo/hormonal therapy for 3 x 8-week courses, followed by total androgen blockade. Each course consists of 6 weeks of cytotoxic therapy with doxorubicin, ketoconazole, vinblastine, and estramustine followed by 2 weeks rest. Maintained on hydrocortisone both during treatment and during rest.

    Drug: Doxorubicin hydrochloride
    Other Names:
  • Adriamycin
  • Adriamycin PFS
  • Adriamycin RDF
  • Rubex
  • Drug: Estramustine Phosphate Sodium
    Other Names:
  • Emcyt
  • Drug: Ketoconazole
    Other Names:
  • Nizoral
  • Drug: Therapeutic Hydrocortisone
    Other Names:
  • A-hydroCort
  • Cortef
  • Cortenema
  • Cortifoam
  • Hydrocortone
  • Solu-Cortef
  • Drug: Vinblastine
    Other Names:
  • Velban
  • Outcome Measures

    Primary Outcome Measures

    1. Time to Progression [From baseline to post treatment (minimally 24+ weeks)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    DISEASE CHARACTERISTICS:
    • Histologically proven acinar adenocarcinoma of the prostate

    • Metastatic or locally advanced disease that either is not appropriately treated with surgery or radiation, or has recurred following previous "definitive" local therapy

    • No CNS metastases

    • No histologic subtypes, such as pure ductal or any component of small cell carcinoma

    • Elevated PSA (at least 1.0 ng/mL in patients with prior prostatectomy or 4.0 ng/mL in those with prostate in place)

    PATIENT CHARACTERISTICS:
    Age:
    • Not specified
    Performance status:
    • Zubrod 0-2
    Life expectancy:
    • At least 3 years
    Hematopoietic:
    • Absolute neutrophil count greater than 1,500/mm^3

    • Platelet count greater than 100,000/mm^3

    Hepatic:
    • Conjugated bilirubin no greater than 0.8 mg/dL or total bilirubin no greater than 1.5 mg/dL

    • Transaminase no greater than 4 times upper limit of normal

    Renal:
    • Creatinine clearance at least 40 mL/min
    Cardiovascular:
    • No evidence of bifascicular block on EKG

    • No evidence of active ischemia on EKG

    • No prior history of transient ischemic attack

    • No evidence of congestive heart failure

    Other:
    • No active peptic ulcer disease

    • No regular use of antacid or H2 blockers

    • No known or predicted achlorhydria

    • No concurrent use of terfenadine, astemizole, omeprazole, or cisapride

    • No second malignancy unless curatively treated

    • No history of deep venous thrombosis

    • No history of pulmonary embolism

    • No serious co-morbidity

    • HIV negative

    PRIOR CONCURRENT THERAPY:
    Biologic therapy:
    • Not specified
    Chemotherapy:
    • No prior cytotoxic systemic therapy
    Endocrine therapy:
    • Prior androgen deprivation therapy allowed if given for no more than 6 months to downstage primary

    • No androgen deprivation therapy within 1 year prior to study

    Radiotherapy:
    • No prior cytotoxic systemic therapy (including systemic strontium-89 irradiation)

    • Prior definitive radiotherapy to the prostate and/or one metastatic site allowed

    • At least 8 weeks since radiotherapy to the pelvis

    • At least 3 weeks since radiotherapy to a single metastatic site

    Surgery:
    • Prior prostatectomy allowed
    Other:
    • No concurrent anti-anginal therapy or aggressive anticoagulants

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Texas - MD Anderson Cancer Center Houston Texas United States 77030-4009

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Study Chair: Randall E. Millikan, MD, PhD, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00002855
    Other Study ID Numbers:
    • DM95-231
    • P30CA016672
    • MDA-DM-95231
    • NCI-G96-1044
    • CDR0000065105
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Oct 31, 2018
    Last Verified:
    Oct 1, 2018

    Study Results

    No Results Posted as of Oct 31, 2018