Toremifene Followed by Radical Prostatectomy in Treating Patients With Stage I or Stage II Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Study type: Interventional
Phase: Phase 2

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.
    

Detailed 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.
    

Intervention name(s): toremifene; conventional surgery; neoadjuvant therapy
Intervention type(s): Drug; Procedure; Procedure
Intervention MeSH terms: Toremifene
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: adenocarcinoma of the prostate; stage I prostate cancer; stage II prostate cancer