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

NCT ID: NCT00086736

Last Updated: 2013-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-11-30
• Study Completion Date: 2003-11-30

Brief Summary

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.

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.

Conditions

Prostate Cancer

Keywords

stage I prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer; stage III prostate cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

bicalutamide

Intervention Type: DRUG

eflornithine

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

eflornithine

Intervention Type: DRUG

oral bicalutamide placebo

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

bicalutamide

Intervention Type: DRUG

oral eflornithine placebo

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

oral eflornithine placebo

Intervention Type: DRUG

oral bicalutamide placebo

Intervention Type: DRUG

Interventions

bicalutamide

Intervention Type: DRUG

eflornithine

Intervention Type: DRUG

oral eflornithine placebo

Intervention Type: DRUG

oral bicalutamide placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald A. Urban, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, United States

Countries

United States

Other Identifiers

UAB-9921

Identifier Type: -

Identifier Source: secondary_id

UAB-F990728039

Identifier Type: -

Identifier Source: secondary_id

CDR0000353198

Identifier Type: -

Identifier Source: org_study_id