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Clinical Trial Summary

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.


Clinical Trial Description

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. ;


Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention


Related Conditions & MeSH terms


NCT number NCT00020735
Study type Interventional
Source University of Pittsburgh
Contact
Status Completed
Phase Phase 2
Start date April 2001
Completion date June 2009

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