Official Title: “A Randomized, Placebo-Controlled Phase IIb Clinical Trial of 2-Difluoromethylornithine (DFMO) Versus Bicalutamide (CASODEX) Alone and in Combination in Patients With Prostate Cancer in the Period Prior to Radical Prostatectomy or Brachytherapy: Modulation of Tissue and Molecular Biomarkers in Human Prostate Tissue Serum”

RATIONALE: Drugs used in chemotherapy, such as eflornithine, work in different ways to stop tumor cells from dividing so they stop growing or die.

Androgens can stimulate the growth of prostate cancer cells. Drugs used in hormone therapy, such as bicalutamide, may fight prostate cancer by stopping the adrenal glands from producing androgens. Combining eflornithine with bicalutamide may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of neoadjuvant eflornithine and bicalutamide with that of eflornithine alone, bicalutamide alone, and no neoadjuvant therapy in treating patients who are undergoing brachytherapy or radical prostatectomy for localized prostate cancer.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control

OBJECTIVES: - Compare levels of polyamine spermine, polyamine putrescine, and spermidine in patients with localized prostate cancer undergoing brachytherapy or radical prostatectomy and treated with neoadjuvant eflornithine and bicalutamide vs eflornithine alone vs bicalutamide alone vs no neoadjuvant therapy. - Compare the expression of surrogate biomarkers (i.e., serum prostate-specific antigen, tissue levels of proliferating cell nuclear antigen, Ki67, and TGF-alpha, apoptosis assays [ICH-PARP and TUNEL], and cytomorphometric indices) in patients treated with these regimens. - Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to Gleason score (< 7 vs ≥ 7). Patients are randomized to 1 of 4 treatment arms. - Arm I: Patients receive oral eflornithine and oral bicalutamide once daily. - Arm II: Patients receive oral eflornithine and oral bicalutamide placebo once daily. - Arm III: Patients receive oral eflornithine placebo and oral bicalutamide once daily. - Arm IV: Patients receive oral eflornithine placebo and oral bicalutamide placebo once daily.

In all arms, treatment continues for 28 days in the absence of unacceptable toxicity.

Patients then undergo either prostatectomy or brachytherapy, as determined by the patient, on day 29.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 44 patients (11 per treatment arm) will be accrued for this study within 11 months.

Intervention(s) in this Clinical Trial

• Drug: bicalutamide
• Drug: eflornithine
• Procedure: conventional surgery
• Radiation: brachytherapy

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer
• Localized disease
• Paraffin blocks from diagnostic biopsies available
• Planning to undergo brachytherapy or prostatectomy

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• ECOG 0-3
• Life expectancy
• Not specified
• Hematopoietic
• Hemoglobin ≥ 10.0 g/dL
• WBC ≥ 3,500/mm^3
• Platelet count ≥ 125,000/mm^3
• Hepatic
• Bilirubin ≤ 2.0 mg/dL
• SGOT and SGPT ≤ 2 times normal
• No history of liver disease (e.g., hepatitis, cirrhosis, or jaundice)
• Renal
• Creatinine ≤ 2.0 mg/dL
• Cardiovascular
• No symptomatic coronary artery disease
• No uncontrolled hypertension
• No acute myocardial infarction within the past year
• Other
• Fertile patients must use effective contraception
• No more than 10 decibels baseline hearing loss at any frequency by full bilateral audiometry within the past month
• No hypersensitivity to eflornithine or bicalutamide
• No other prior or active malignancy except nonmelanoma skin cancer or other cancer curatively treated at least 5 years ago with no evidence of recurrent or residual disease
• No concurrent acute or chronic medical or psychiatric condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• No concurrent immunotherapy
• Chemotherapy
• No other concurrent chemotherapy
• Endocrine therapy
• More than 1 year since prior antiandrogen, luteinizing hormone-releasing hormone (LHRH) agonist, bicalutamide, finasteride, or diethylstilbestrol
• No other concurrent antiandrogen, LHRH agonist, finasteride, or diethylstilbestrol
• Radiotherapy
• See Disease Characteristics
• No other concurrent radiotherapy
• Surgery
• See Disease Characteristics

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Alabama at Birmingham

Overall Clinical Trial Officials and Contacts

Donald A. Urban, MD Principal Investigator University of Alabama at Birmingham  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00086736

Study ID Number: CDR0000353198

ClinicalTrials.gov Identifier: NCT00086736

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database