Toremifene Followed by Radical Prostatectomy in Treating Patients With Stage I or Stage II 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 toremifene may fight prostate cancer by reducing the production of androgens. PURPOSE: Randomized phase II trial to study the effectiveness of toremifene followed by radical prostatectomy in treating patients who have stage I or stage II prostate cancer.

Detailed Description
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OBJECTIVES: Compare the percent of high-grade prostatic intraepithelial neoplasia (HGPIN) present in the radical prostatectomy tissue (excluding the luminal area) of patients with stage I or II adenocarcinoma of the prostate treated with toremifene vs observation alone followed by radical prostatectomy. Compare the absolute and relative changes in HGPIN in patients treated with toremifene vs observation alone. Compare biomarkers (including DNA ploidy and nuclear morphology; Ki67 and MIB-1 expression; bcl-2 expression; frequency of cells expressing apoptotic bodies; microvessel density; and intraprostatic testosterone, dihydrotestosterone (DHT), and estradiol) in the radical prostatectomy tissue of patients treated with toremifene vs observation alone. Compare changes from baseline in serum biomarkers, particularly PSA and hormone profiles (testosterone, DHT, androstenedione, dehydroepiandrosterone, androstanediol-glucuronide, estradiol, and sex hormone binding globulin), in patients treated with toremifene vs observation alone. Compare the safety of toremifene in these patients. Determine the relationships among pairs of biomarkers, biomarker changes, and outcome measures, including toxicity of toremifene and posttreatment HGPIN in these patients. Determine the relationship between HGPIN or biomarker responses and antiandrogen germline CAG repeat length polymorphism in patients treated with toremifene. Compare the tumor volume, margin status, and pT stage in patients treated with toremifene vs observation alone. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center and baseline high-grade prostatic intraepithelial neoplasia (none vs more than 0% up to 10% vs more than 10%). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral toremifene daily for 3-6 weeks in the absence of unacceptable toxicity. Arm II: Patients undergo observation alone. Patients in both arms then undergo radical prostatectomy. PROJECTED ACCRUAL: A total of 78 patients (52 for arm I, 26 for arm II) will be accrued for this study at a rate of 6-7 patients per month.

Official Title
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A Phase II Randomized Controlled Clinical Trial Of The Antiestrogen GTx-006 In Subjects With Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: toremifene
* 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 Organ-confined (cT1-2) disease (stage I or II) Must be schedule to undergo radical prostatectomy Prior sextant biopsy required PATIENT CHARACTERISTICS: Age: Over 18 Performance status: ECOG 0-1 Life expectancy: Not specified Hematopoietic: Neutrophil count greater than 1,500/mm^3 Platelet count greater than 100,000/mm^3 Hepatic: Bilirubin less than 1.5 times upper limit of normal (ULN) ALT and AST less than 2 times ULN Alkaline phosphatase less than 2 times ULN No chronic hepatitis or cirrhosis Renal: Creatinine less than 1.5 times ULN Other: No severe mental or physical illness that would preclude radical prostatectomy Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: At least 5 years since prior antiestrogen, antiandrogen, LHRH agonist, estrogen, or progestational agent Radiotherapy: Not specified Surgery: See Disease Characteristics

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: oral toremifene<br> | Drug: toremifene<br> <br> Procedure: neoadjuvant therapy<br> <br> |
| Other: observation<br> | Procedure: conventional surgery<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of radical prostatectomy tissue volume (exclusive of luminal area) with high-grade prostatic intraepithelial neoplasia (HGPIN) present |  |  | 

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