Neoadjuvant Exisulind in Treating Patients Who Are Undergoing Radical Prostatectomy for Stage II or Stage III Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as exisulind, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink the tumor so that it can be removed. PURPOSE: This phase II trial is studying how well neoadjuvant exisulind works in treating patients who are undergoing radical prostatectomy for stage II or stage III prostate cancer.

Detailed Description
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OBJECTIVES: Primary Compare the effect of neoadjuvant exisulind vs no neoadjuvant treatment on apoptosis in patients with stage II or III prostate cancer undergoing radical prostatectomy. Secondary Determine the effect of this drug (preoperatively) on surrogate endpoint biomarkers (i.e., prostate-specific antigen, high-grade prostatic intraepithelial neoplasia, MIB-1, and DNA ploidy) in these patients. OUTLINE: This is a nonrandomized, controlled study. Patients are assigned to 1 of 2 groups based on the treating physician. Control group: Patients undergo radical prostatectomy only. Treatment group: Patients receive oral exisulind once daily for 4 weeks. Patients then undergo radical prostatectomy. Patients are followed at 1 month. PROJECTED ACCRUAL: A total of 130 patients (65 per group) will be accrued for this study within approximately 10-12 months.

Official Title
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A Prospective Phase II Study of Preoperative, Controlled Exisulind Therapy Initiated Prior to Radical Prostatectomy: Effect on Apoptosis

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: exisulind
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Clinical stage T1c-3b, N0-X, M0 Gleason score ≥ 6 Planning to undergo pelvic lymphadenectomy and radical prostatectomy at Mayo Clinic Rochester Interval from biopsy to prostatectomy is at least 4, but no more than 14, weeks Selected patients of Dr. R. P. Myers who are undergoing prostatectomy during the enrollment period will be assigned to the control group* NOTE: *Additional historical controls may be selected from Dr. Myers' patients who underwent prostatectomy within the past 4 years PATIENT CHARACTERISTICS: Age 40 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Not specified Hepatic ALT normal (10-45 U/L) AST normal (12-31 U/L) Alkaline phosphatase normal (119-309 U/L) Bilirubin normal (0.1-1.0 mg/dL) No history of hepatitis, cirrhosis, or other hepatic dysfunction Renal Creatinine < 1.5 mg/dL Other Fertile patients must use effective contraception No hypersensitivity to sulindac (treatment group) PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy Chemotherapy No other concurrent chemotherapy Endocrine therapy No prior ablation (treatment group) No prior hormone replacement or antiandrogen therapy (e.g., testosterone, diethylstilbestrol, leuprolide, goserelin, flutamide, bicalutamide, finasteride, nilutamide, or megestrol) No concurrent antiandrogen therapy, luteinizing hormone-releasing hormone agonists, finasteride, or diethylstilbestrol Radiotherapy No prior pelvic radiotherapy No concurrent radiotherapy Surgery See Disease Characteristics Other No prior treatment for prostate cancer before prostatectomy (control group) No concurrent cyclooxygenase-2 inhibitors No concurrent sulindac No concurrent nonsteroidal anti-inflammatory drugs except low-dose (no more than 325 mg/day) aspirin for cardiovascular prophylaxis

Ages Eligible for Study
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Minimum Age: 40 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: Non-Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: exisulind|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apoptosis 4 weeks after completion of study as assessed by marker analysis (bcl-2, Bax, Par-4, M30, TUNEL assay, PTEN) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modulation of other surrogate endpoint biomarkers (prostate-specific antigen high-grade prostatic intraepithelial neoplasia, MIB-1, and DNA ploidy) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer