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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00086736
First received: July 8, 2004
Last updated: November 17, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: bicalutamide
Drug: eflornithine
Drug: oral eflornithine placebo
Drug: oral bicalutamide placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Mean difference in levels of Polyamine spermine, polyamine putrescine, and spermidine between subjects in each of the 4 groups [ Time Frame: 4 weeks after surgical intervention ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: November 2001
Study Completion Date: November 2003
Primary Completion Date: November 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 eflornithine placebo Drug: oral bicalutamide 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086736

Locations
United States, Alabama
University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294-3300
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Donald A. Urban, MD University of Alabama at Birmingham
  More Information

Additional Information:
No publications provided

Responsible Party: University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00086736     History of Changes
Other Study ID Numbers: CDR0000353198, UAB-9921, UAB-F990728039
Study First Received: July 8, 2004
Last Updated: November 17, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Alabama at Birmingham:
stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Bicalutamide
Eflornithine
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 18, 2014