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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: bicalutamide
* Drug: eflornithine
* Drug: oral eflornithine placebo
* Drug: oral bicalutamide placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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<br> <br> Drug: eflornithine<br> <br> |
| Experimental: Arm II<br>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<br> <br> Drug: oral bicalutamide placebo<br> <br> |
| Experimental: Arm III<br>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<br> <br> Drug: oral eflornithine placebo<br> <br> |
| Experimental: Arm IV<br>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 eflornithine placebo<br> <br> Drug: oral bicalutamide placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer