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

Study Overview
=================
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.

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.

Official Title
-----------------
A Phase 3 Trial of Androgen Ablation Alone vs. Chemo/Hormonal Therapy as Initial Treatment of Unresectable/Metastatic Adenocarcinoma of the Prostate

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Bicalutamide
* Drug: Doxorubicin hydrochloride
* Drug: Estramustine Phosphate Sodium
* Drug: Flutamide
* Drug: Ketoconazole
* Drug: Nilutamide
* Drug: Therapeutic Hydrocortisone
* Drug: Vinblastine
* Procedure: Conventional Surgery


Participation Criteria
=================
Eligibility 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
Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Arm I: Medical or surgical castration followed by an anti-androgen therapy with either flutamide, bicalutamide, or nilutamide. | Drug: Bicalutamide<br> <br> * Other names: Casodex;Drug: Flutamide<br> <br> * Other names: Eulexin;Drug: Nilutamide<br> <br> * Other names: Nilandron;Procedure: Conventional Surgery<br>* Surgical castration<br>* Other names: Castration;|
| Experimental: Arm II<br>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<br> <br> * Other names: Rubex;Drug: Estramustine Phosphate Sodium<br> <br> * Other names: Emcyt;Drug: Ketoconazole<br> <br> * Other names: Nizoral;Drug: Therapeutic Hydrocortisone<br> <br> * Other names: Solu-Cortef;Drug: Vinblastine<br> <br> * Other names: Velban;|

What is the study measuring?
-----------------
Primary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenocarcinoma of the prostate, stage III prostate cancer, stage IV prostate cancer, recurrent prostate cancer