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
  Purpose

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 Intervention Phase
Prostate Cancer
Drug: Bicalutamide
Drug: Doxorubicin hydrochloride
Drug: Estramustine Phosphate Sodium
Drug: Flutamide
Drug: Ketoconazole
Drug: Nilutamide
Drug: Therapeutic Hydrocortisone
Drug: Vinblastine
Procedure: Conventional Surgery
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Time to Progression [ Time Frame: From baseline to post treatment (minimally 24+ weeks) ] [ Designated as safety issue: No ]

Enrollment: 306
Study Start Date: August 1996
Study Completion Date: June 2005
Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Arm I: Medical or surgical castration followed by an anti-androgen therapy with either flutamide, bicalutamide, or nilutamide.
Drug: Bicalutamide
Other Name: Casodex
Drug: Flutamide
Other Name: Eulexin
Drug: Nilutamide
Other Names:
  • Anandron
  • Nilandron
Procedure: Conventional Surgery
Surgical castration
Other Name: 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 Name: Emcyt
Drug: Ketoconazole
Other Name: Nizoral
Drug: Therapeutic Hydrocortisone
Other Names:
  • A-hydroCort
  • Cortef
  • Cortenema
  • Cortifoam
  • Hydrocortone
  • Solu-Cortef
Drug: Vinblastine
Other Name: Velban

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.

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
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: NCT00002855

Locations
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Randall E. Millikan, MD, PhD M.D. Anderson Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00002855     History of Changes
Other Study ID Numbers: DM95-231, P30CA016672, MDA-DM-95231, NCI-G96-1044, CDR0000065105
Study First Received: November 1, 1999
Last Updated: July 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
adenocarcinoma of the prostate
stage III prostate cancer
stage IV prostate cancer
recurrent prostate cancer

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Androgens
Doxorubicin
Liposomal doxorubicin
Nilutamide
Bicalutamide
Estramustine
Flutamide
Vinblastine
Ketoconazole
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Hydrocortisone-17-butyrate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on July 31, 2014