Extension to Study of Effects of Pomegranate Extract on Rising PSA Levels After Primary Therapy for Prostate Cancer

• The mean change in PSA doubling time from baseline to end-of-treatment. [ Time Frame: 48 months ] [ Designated as safety issue: No ]
• Response rates in positive and negative PSA doubling times with a clinically significant positive doubling time is defined as >150% of baseline. [ Time Frame: 48 months ] [ Designated as safety issue: No ]
• Overall efficacy responses categorized as Objective Response, Progressive Disease, Stable Disease. [ Time Frame: 48 months ] [ Designated as safety issue: No ]
• Measures of tolerability (adverse events) and toxicity (clinical chemistries, etc.). [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]

High concentrations of anti-oxidants in pomegranate seeds present a potential strategy to delay clinical prostate cancer progression and prolong the interval from primary treatment failure to hormonal ablation. This is a 48 month extension to the double-blind GUP-0205-1 study, to compare the effects of daily consumption of pomegranate liquid extract versus placebo on the absolute prostate-specific antigen (PSA) doubling time at the end of 12, 24, 36 and 48 months in male subjects who rolled-over from the GUP-0205-1 study.

The primary objectives are to compare the effects of daily consumption of pomegranate liquid extract versus placebo on the absolute prostate-specific antigen (PSA) doubling time at the end of 12,24, 36 and 48 months in male subjects who rolled-over from the GUP-0205-1 study. Secondary objectives are to determine the effect of the pomegranate treatment on the change in PSA doubling time from baseline to each 12-month visit, to determine the time to tumor recurrence, to assess the tolerability and toxicity of the pomegranate treatment and to determine the effect of the pomegranate treatment on response rates for positive PSA doubling times and for declining post-treatment PSA levels (negative doubling times).

• Dietary Supplement: pomegranate extract
  8 oz per day, 48 months
• Dietary Supplement: pomegranate juice
  8 oz per day, 48 months
  Other Name: PomWonderful
• Dietary Supplement: placebo
  8 oz per day, 48 months

• Experimental: 1
  Intervention: Dietary Supplement: pomegranate extract
• Experimental: 2
  Intervention: Dietary Supplement: pomegranate juice
• Placebo Comparator: 3
  Intervention: Dietary Supplement: placebo

Inclusion Criteria:

• No evidence of disease progression while on any of the three GUP-0205 study products (disease progression defined as > 100% increase in serum PSA [with a minimum value of 1.0 ng/mL]).
• Willingness and ability to sign an informed consent document.
• Agreement with complete abstinence from other commercially available pomegranate products during the course of the study.
• Use of dietary/herbal supplements (e.g., saw palmetto, selenium, etc) is acceptable provided the dose has been stable during the course of the GUP-0205- 1 study.

Exclusion Criteria:

• Significant concomitant medical or psychiatric condition that, in the opinion of the Principal Investigator, would put the subject at risk or compromise the protocol.
• Hormonal therapy, with the exception of neoadjuvant androgen deprivation therapy (ADT) prior to or concurrent with primary therapy. Subjects who underwent neoadjuvant ADT cannot have a serum testosterone of ≤150 ng/mL at study entry.
• Concomitant or antecedent hormonal therapy for rising serum PSA after initial therapy of prostate cancer.
• Subjects unable or unwilling to comply with protocol requirements.
• Prior treatment with experimental drugs, high dose steroids, or with any other cancer treatment within 4 weeks prior to the first dose of study product and for the duration of the study.
• Serum PSA >7.0 ng/mL (assessed at termination of the double-blind study; at any PSA level, the subject will be excluded if determined by the Principal Investigator that the subject's continued participation would not be in their best interest).
• Serum PSA doubling time <13 weeks (assessed at termination of the double-blind study).
• Evidence of metastatic disease on physical examination or on CT or bone scan.
• Use of finasteride, dutasteride at any point since primary therapy or during the study.
• Clinically significant abnormal laboratory value greater than 2 times the upper limit of normal (>2XULN).