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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Active Control

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.

Intervention(s) in this Clinical Trial

• Drug: bicalutamide
• Drug: exemestane

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

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Swiss Group for Clinical Cancer Research

Overall Clinical Trial Officials and Contacts

Marco Bonomo, MD Study Chair Ospedale Beata Vergine  

Information obtained from ClinicalTrials.gov on January 06, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00031889

Study ID Number: CDR0000069237

ClinicalTrials.gov Identifier: NCT00031889

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database