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

October 30, 2018 updated by: M.D. Anderson Cancer Center

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.

Study Overview

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 Type

Interventional

Enrollment (Actual)

306

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Texas
      • Houston, Texas, United States, 77030-4009
        • University of Texas - MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
Arm I: Medical or surgical castration followed by an anti-androgen therapy with either flutamide, bicalutamide, or nilutamide.
Other Names:
  • Casodex
Other Names:
  • Eulexin
Other Names:
  • Anandron
  • Nilandron
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.
Other Names:
  • Nizoral
Other Names:
  • Velban
Other Names:
  • Adriamycin
  • Adriamycin PFS
  • Adriamycin RDF
  • Rubex
Other Names:
  • Emcyt
Other Names:
  • Cortef
  • Cortenema
  • Hydrocortone
  • Solu-Cortef
  • A-hydroCort
  • Cortifoam

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time to Progression
Time Frame: From baseline to post treatment (minimally 24+ weeks)
From baseline to post treatment (minimally 24+ weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 1996

Primary Completion (Actual)

June 1, 2005

Study Completion (Actual)

June 1, 2005

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

October 31, 2018

Last Update Submitted That Met QC Criteria

October 30, 2018

Last Verified

October 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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