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

Sponsor

Joel Nelson, MD (Other)

Overall Status

Completed

CT.gov ID

NCT00020735

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: toremifene Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Apr 1, 2001

Actual Primary Completion Date :

Jan 1, 2005

Actual Study Completion Date :

Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: oral toremifene	Drug: toremifene Procedure: neoadjuvant therapy
Other: observation	Procedure: conventional surgery

Arm

Intervention/Treatment

Experimental: oral toremifene

Drug: toremifene

Procedure: neoadjuvant therapy

Other: observation

Procedure: conventional surgery

Outcome Measures

Primary Outcome Measures

Percent of radical prostatectomy tissue volume (exclusive of luminal area) with high-grade prostatic intraepithelial neoplasia (HGPIN) present []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232

Sponsors and Collaborators

Joel Nelson, MD
National Cancer Institute (NCI)

Investigators

Study Chair: Joel B. Nelson, MD, University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Joel Nelson, MD, Professor and Chairman, Department of Urology, University of Pittsburgh School of Medicine; Chief, Division of Surgery, UPMC Shadyside Hospital, University of Pittsburgh

ClinicalTrials.gov Identifier:

NCT00020735

Other Study ID Numbers:

PCI-00-105
CDR0000068708
PCI-N01-CN-75018
NCI-P01-0181

First Posted:

Jan 27, 2003

Last Update Posted:

Dec 2, 2015

Last Verified:

Dec 1, 2015

Keywords provided by Joel Nelson, MD, Professor and Chairman, Department of Urology, University of Pittsburgh School of Medicine; Chief, Division of Surgery, UPMC Shadyside Hospital, University of Pittsburgh

adenocarcinoma of the prostate

stage I prostate cancer

stage II prostate cancer

Additional relevant MeSH terms:

Prostatic Neoplasms

Toremifene

Study Results

No Results Posted as of Dec 2, 2015