Toremifene Followed by Radical Prostatectomy in Treating Patients With Stage I or Stage II Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00020735
• Other study ID #: PCI-00-105
• Secondary ID: CDR0000068708PCI
• Status: Completed
• Phase: Phase 2
• First received: July 11, 2001
• Last updated: December 1, 2015
• Start date: April 2001
• Est. completion date: June 2009

Study information

• Verified date: December 2015
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: June 2009
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 120 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• toremifene

Procedure:
• conventional surgery

• neoadjuvant therapy

Locations

Country	Name	City	State
United States	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Joel Nelson, MD	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of radical prostatectomy tissue volume (exclusive of luminal area) with high-grade prostatic intraepithelial neoplasia (HGPIN) present			No