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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00002855
First received: November 1, 1999
Last updated: July 27, 2012
Last verified: July 2012

November 1, 1999
July 27, 2012
August 1996
June 2005   (final data collection date for primary outcome measure)
Time to Progression [ Time Frame: From baseline to post treatment (minimally 24+ weeks) ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00002855 on ClinicalTrials.gov Archive Site
Not Provided
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Not Provided
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Chemotherapy Plus Hormone Therapy Versus Androgen Suppression in Treating Patients With Metastatic or Unresectable Prostate Cancer
A Phase 3 Trial of Androgen Ablation Alone vs. Chemo/Hormonal Therapy as Initial Treatment of Unresectable/Metastatic Adenocarcinoma of the Prostate

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Drug: Bicalutamide
    Other Name: Casodex
  • Drug: Doxorubicin hydrochloride
    Other Names:
    • Adriamycin
    • Adriamycin PFS
    • Adriamycin RDF
    • Rubex
  • Drug: Estramustine Phosphate Sodium
    Other Name: Emcyt
  • Drug: Flutamide
    Other Name: Eulexin
  • Drug: Ketoconazole
    Other Name: Nizoral
  • Drug: Nilutamide
    Other Names:
    • Anandron
    • Nilandron
  • Drug: Therapeutic Hydrocortisone
    Other Names:
    • A-hydroCort
    • Cortef
    • Cortenema
    • Cortifoam
    • Hydrocortone
    • Solu-Cortef
  • Drug: Vinblastine
    Other Name: Velban
  • Procedure: Conventional Surgery
    Surgical castration
    Other Name: Castration
  • Experimental: Arm I
    Arm I: Medical or surgical castration followed by an anti-androgen therapy with either flutamide, bicalutamide, or nilutamide.
    Interventions:
    • Drug: Bicalutamide
    • Drug: Flutamide
    • Drug: Nilutamide
    • Procedure: Conventional Surgery
  • 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.
    Interventions:
    • Drug: Doxorubicin hydrochloride
    • Drug: Estramustine Phosphate Sodium
    • Drug: Ketoconazole
    • Drug: Therapeutic Hydrocortisone
    • Drug: Vinblastine
Millikan RE, Wen S, Pagliaro LC, Brown MA, Moomey B, Do KA, Logothetis CJ. Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. J Clin Oncol. 2008 Dec 20;26(36):5936-42. Epub 2008 Nov 24.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
306
June 2005
June 2005   (final data collection date for primary outcome measure)

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
Male
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00002855
DM95-231, P30CA016672, MDA-DM-95231, NCI-G96-1044, CDR0000065105
No
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Study Chair: Randall E. Millikan, MD, PhD M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP