Neoadjuvant Eflornithine and Bicalutamide Compared With Eflornithine Alone, Bicalutamide Alone, and No Neoadjuvant Therapy in Treating Patients With Localized Prostate Cancer Undergoing Brachytherapy or Radical Prostatectomy

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 Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: bicalutamide; Drug: eflornithine; Drug: oral bicalutamide placebo; Drug: oral eflornithine placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive oral eflornithine and oral bicalutamide once daily for 28 days in the absence of unacceptable toxicity. Patients then undergo either prostatectomy or brachytherapy, as determined by the patient, on day 29.	Drug: bicalutamide; Drug: eflornithine
Experimental: Arm II; Patients receive oral eflornithine and oral bicalutamide placebo once daily for 28 days in the absence of unacceptable toxicity. Patients then undergo either prostatectomy or brachytherapy, as determined by the patient, on day 29.	Drug: eflornithine; Drug: oral bicalutamide placebo
Experimental: Arm III; Patients receive oral eflornithine placebo and oral bicalutamide once daily for 28 days in the absence of unacceptable toxicity. Patients then undergo either prostatectomy or brachytherapy, as determined by the patient, on day 29.	Drug: bicalutamide; Drug: oral eflornithine placebo
Experimental: Arm IV; Patients receive oral eflornithine placebo and oral bicalutamide placebo once daily for 28 days in the absence of unacceptable toxicity. Patients then undergo either prostatectomy or brachytherapy, as determined by the patient, on day 29.	Drug: oral bicalutamide placebo; Drug: oral eflornithine placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean difference in levels of Polyamine spermine, polyamine putrescine, and spermidine between subjects in each of the 4 groups	4 weeks after surgical intervention

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Donald A. Urban, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: November 1, 2001
• Primary Completion (Actual): November 1, 2003
• Study Completion (Actual): November 1, 2003

Study Registration Dates

• First Submitted: July 8, 2004
• First Submitted That Met QC Criteria: July 9, 2004
• First Posted (Estimate): July 12, 2004

Study Record Updates

• Last Update Posted (Estimate): November 19, 2013
• Last Update Submitted That Met QC Criteria: November 17, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: stage III prostate cancer; stage I prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Antiprotozoal Agents; Antiparasitic Agents; Androgen Antagonists; Trypanocidal Agents; Ornithine Decarboxylase Inhibitors; Bicalutamide; Eflornithine
• Other Study ID Numbers: CDR0000353198; UAB-9921; UAB-F990728039