Exemestane With or Without Bicalutamide in Treating Patients With Stage IV Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using exemestane plus bicalutamide may fight prostate cancer by reducing the production of androgens. It is not yet known if exemestane is more effective with or without bicalutamide in treating prostate cancer. PURPOSE: Randomized phase II trial to study the effectiveness of exemestane with or without bicalutamide in treating patients who have stage IV prostate cancer that has been previously treated with hormone therapy or surgery.

Detailed Description
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OBJECTIVES: Compare the efficacy and tolerability of exemestane with or without bicalutamide as second-line therapy after failure of androgen suppression (luteinizing hormone-releasing hormone agonist or orchiectomy) in patients with stage IV prostate cancer. Determine the potential antagonistic effect of the weak androgen action of exemestane when combined with bicalutamide in these patients. Compare the quality of life (QOL) in patients treated with these regimens. Correlate prostate-specific antigen response and data of QOL, including scores for pain intensity and analgesic consumption, in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (0 vs 1-2), pain (none or mild vs moderate or severe), and participating center. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral exemestane once daily. Arm II: Patients receive exemestane as in arm I and oral bicalutamide once daily. Treatment in both arms continues every 4 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity. Quality of life and pain are assessed at baseline, on day 1 of course 2 and any subsequent courses, and at disease progression or treatment failure (if applicable). Patients are followed monthly until disease progression. PROJECTED ACCRUAL: A total of 20-62 patients (10-31 per treatment arm) will be accrued for this study.

Official Title
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A Randomized Phase II Trial of Exemestane With and Without Bicalutamide as Second Line Therapy After Failure of Androgen Suppression in Advanced Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Exemestane
* Drug: Exemestane+bicalutamide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed stage IV adenocarcinoma of the prostate Documented disease progression based on prostate-specific antigen (PSA) progression during first-line androgen suppression (luteinizing hormone-releasing hormone agonist or orchiectomy) PSA progression is defined by the following: Interval of at least 1 week between reference value (time point value 1) and the next PSA level (time point value 2) PSA at time point value 3 is greater than PSA at time point value 2 OR PSA at time point value 3 is not greater than PSA at time point value 2, but PSA at time point value 4 is greater than PSA at time point value 2 PSA at least 5 ng/mL Must continue primary androgen suppression if no prior surgical castration No known leptomeningeal or brain metastases PATIENT CHARACTERISTICS: Age: 18 and over Performance status: WHO 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm^3 Neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST and ALT no greater than 2.5 times ULN Renal: Creatinine no greater than 1.5 times ULN Other: No acute concurrent severe infection No other concurrent significant disease that would preclude study therapy No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: No prior antibody or gene therapy Chemotherapy: No prior cytostatic agents Endocrine therapy: See Disease Characteristics No prior estramustine No prior antiandrogens (e.g., bicalutamide) No concurrent estrogen-containing medicine Radiotherapy: More than 4 weeks since prior radiotherapy No concurrent radiotherapy to more than 1 field Surgery: See Disease Characteristics Other: At least 4 weeks since prior investigational drugs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients receive oral exemestane once daily | Drug: Exemestane<br>* Exemestane<br>|
| Active Comparator: Arm II<br>Patients receive exemestane as in arm I and oral bicalutamide once daily | Drug: Exemestane+bicalutamide<br>* Exemestane as in arm I and oral bicalutamide once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

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