Pomegranate Extract in Treating Patients With Rising Prostate-Specific Antigen Levels After Surgery or Radiation Therapy for Localized Prostate Cancer

OBJECTIVES:

Primary

• Evaluate the effects of pomegranate extract in patients with and rising prostate-specific antigen (PSA) levels after surgery or radiotherapy for localized prostate cancer.
• Determine the effect of a daily oral dose of pomegranate extract on the absolute value of PSA and on the change in PSA doubling time in these patients.

Secondary

• Assess toxicities associated with daily oral dosing of pomegranate extract in these patients.
• Determine the effect of pomegranate extract on positive PSA doubling-time outcome, defined as greater than 150% baseline or a negative post-treatment PSA doubling time (i.e., declining PSA).

OUTLINE: This is a multicenter, double-blind, placebo-controlled, randomized study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral pomegranate extract daily.
• Arm II: Patients receive oral placebo daily. Treatment in both arms continues for up to 1 year in the absence of disease progression.

PROJECTED ACCRUAL: A total of 180 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate
• Must have completed prior surgery, cryotherapy, or radiotherapy for the primary tumor
• Documented rising prostate-specific antigen (PSA)

• Absolute level of PSA > 0.2 ng/mL after surgery
• Absolute level of PSA > 1.0 ng/mL after radiation or cryotherapy
• Absolute level of PSA ≥ 0.4 ng/mL after multiple treatment modalities (e.g., surgery with radiotherapy or radiotherapy with cryotherapy)
• PSA must be ≥ 100% above best nadir achieved
• PSA doubling time > 3 months or ≤ 24 months

• Patients must have ≥ 3 rising PSA time points above the minimum nadir achieved over ≥ 6 months

• The interval between PSA time points must be > 2 weeks
• PSA ≤ 7.0 ng/mL
• Patients who underwent radical prostatectomy and never achieved undetectable serum PSA after surgery are not eligible
• Gleason score ≤ 7
• No histologically positive lymph nodes
• No evidence of metastatic disease by physical examination, CT scan, or bone scan

PATIENT CHARACTERISTICS:

• Life expectancy ≥ 6 months
• ECOG performance status 0 or 1
• No significant concomitant medical or psychiatric conditions that would limit study compliance
• No known allergies to pomegranate extract
• No known diabetes with hemoglobin A_1c level > 7.0% in the past 3 months

• Diabetic patients entering study who have not had hemoglobin A_1c level measured in the past 3 months must have levels measured at study initiation
• No clinically abnormal laboratory values > 2 times the upper limit of normal

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 4 weeks since prior and no concurrent experimental drugs, high-dose steroids, or other cancer treatment
• No hormonal therapy, with the exception of neoadjuvant androgen-deprivation therapy (ADT), prior to or concurrent with primary therapy

• Patients who received prior neoadjuvant ADT must have serum testosterone ≥ 150 ng/dL
• No prior or concurrent hormonal therapy for rising PSA after primary therapy for prostate cancer
• No finasteride or dutasteride at any time point after primary therapy and during study therapy
• No other concurrent commercial pomegranate products
• No other concurrent systemic or local therapy for prostate cancer
• Concurrent dietary/herbal supplements (e.g., saw palmetto or selenium) allowed provided dose has been stable for ≥ 2 months prior to study entry and there are no plans to change or stop the supplements during study therapy