Eflornithine in Treating Patients At High Risk of Developing Prostate Cancer

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.