Clinical trial NCT00086736: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-07-12
Enrollment: 34
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Mean difference in levels of Polyamine spermine, polyamine putrescine, and spermidine between subjects in each of the 4 groups
timeFrame: 4 weeks after surgical intervention
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Donald A. Urban, MD
role: PRINCIPAL_INVESTIGATOR
References: