Eflornithine in Treating Patients At High Risk of Developing Prostate Cancer

Randomized Placebo-Controlled, Double-Blind Phase IIb Chemoprevention Trial of Difluoromethylornithine in Brothers and First Cousin Males of Familial Prostate Cancer Probands

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. The use of eflornithine (DMFO) may be an effective way to prevent the development of prostate cancer.

PURPOSE: Randomized phase II trial to determine the effectiveness of eflornithine in preventing prostate cancer in patients who are at high risk of developing the disease.

OBJECTIVES:

• Compare the levels of polyamines (putrescine, spermidine, and spermine) and progression-related genes in the prostate tissue of patients at high genetic risk for prostate cancer treated with eflornithine (DFMO) vs placebo.
• Determine the side effects of DFMO and compare them with the biological effect on the prostate gland in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to age (35 to 60 vs 61 to 70) and presence of localized cancer (yes vs no).

All patients receive oral placebo daily for 4 weeks. Patients who are compliant and take the placebo 5-7 days each week are randomized to one of two arms.

• Arm I: Patients receive oral placebo daily.
• Arm II: Patients receive high-dose oral eflornithine (DFMO) daily. Treatment continues for 1 year in the absence of unacceptable toxicity.

PROJECTED ACCRUAL: A total of 100 patients (50 per arm) will be accrued for this study within 3 years.

Criteria for Eligibility

1. Men between the ages of 35 and 70 with family history of prostate cancer, i.e., prostate cancer diagnosed in two first degree relatives before the age of 70 years. (First degree relatives include a brother, father, and son.) There will be occasions in which a second or even third degree relative will be eligible. Additional information regarding these criteria is provided below and in Attachment 1.)

   • Two or more affected relatives of which at least 1 is a first degree relative or
   • At least two affected relatives, both of which are at least a second degree relative or
   • One first degree relative diagnosed with prostate cancer at age 55 or less.

2. No history of invasive cancer within 5 years (though non-melanoma skin or papillary bladder cancer will not be reason to exclude a patient); no prior history of prostate cancer, no severe metabolic disorders or other life-threatening acute or chronic disease; no additional x-ray or chemotherapy anticipated.

   • Men found to have localized prostate cancer (Gleason score ≤7) as part of the screening for the current trial, and opt for watchful waiting as their standard of care treatment for their condition, will be eligible to sign an additional consent form to continue with the randomization and on-study activities of this trial. On-study activities for these individuals will not differ from the on-study activities for the other men enrolled in this trial.

3. Must not require a medically mandated special diet which precludes compliance with study requirements

4. Not requiring regular use of anticoagulants on a regular basis. Prior use of chemoprevention agent(s) (such as Proscar) is allowed as long as the subject has been off the agent(s) for at least 3 months. Not currently participating in another prostate prevention trial.

5. Absence of history of current documented or symptomatic gastric or duodenal ulcer within 12 months prior to study entry, or of significant kidney or liver disease. No chronic anemia (hematocrit < 35 volume %), leukopenia (WEB <4,000) with normal differential, or thrombocytopenia (platelets <100,000) and with serum creatinine <1.5 mg/dl, serum bilirubin <2.0 mg/dl, and serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) <2× normal. Urinalysis should have <1+ protein, 0-3 casts, 0-5 white blood cell count (WBC) and red blood cell count (RBC).

6. Absence of any condition that predisposes to difficulties with hearing, wound healing or repair.

7. Must meet Southwest Oncology Group performance status criteria of 0-1 (0 = fully active, able to carry on all predisease activities without restriction [Karnofsky scale 90-100]; 1 = restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, i.e., light housework or office work [Karnofsky scale 70-80].

8. Subjects must be willing and able to keep required visits for study procedures and to complete study questionnaires.

9. Patient must not have had radiation therapy in the pelvic area.