Trial Information

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

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.