Effects of Two Doses of MPX Capsules on Rising Prostate-specific Antigen Levels in Men Following Initial Therapy for Prostate Cancer

Study Overview
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Brief Summary
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This research is being done to test an investigational product called Muscadine Plus in the treatment of men who have received initial therapy (surgery and or radiation, cryotherapy or brachytherapy) for prostate cancer and are experiencing a rise in their prostate-specific antigens (PSA) level.

Detailed Description
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In phase I the investigators are evaluating the safety of the product and checking blood levels of the active components. In phase II the investigators are evaluating the effect of MPX on PSA doubling time

Official Title
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Phase I/II Study of Safety and Efficacy of Muscadine Plus (MPX) in Men With Prostate Cancer: a Randomized,Double-blind,Placebo Controlled Study of the Effects of Two Doses of MPX Capsules on Rising Prostate-specific Antigen Levels in Men Following Initial Therapy for Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Muscadine Plus Grape Skin Extract
* Drug: Low-dose MPX
* Drug: High-dose MPX
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the prostate. Undergone definitive treatment (surgery, surgery with radiation therapy, cryotherapy, radiation therapy or brachytherapy) for the primary prostate tumor. Rising PSA on a minimum of 3 time points (including screening psa) within the 12 months prior to study initiation. > 18 years of age. Life expectancy of greater than 6 months. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2. Testosterone level of ≥1.5 ng/mL at screening. Adequate kidney, liver and bone marrow function Agrees to abstain from other commercially available MP products while participating in this study. Subject's use of other dietary/herbal supplements (e.g. saw palmetto, selenium, etc) has been stable for at least 2 months prior to screening and the subject agrees not to stop or change the dose(s) while participating in the study. Signed a written informed consent document and agrees to comply with requirements of the study. Exclusion Criteria: Known radiographic evidence of metastatic disease, except for presence of positive lymph nodes from the surgical pathology. Pelvic/intraperitoneal lymph nodes less than 2.0 cm maybe considered nonspecific and the patient would be eligible Receipt of any therapies that modulate testosterone levels (e.g., androgen ablative/anti-androgen therapy, 5 alpha reductase inhibitors) for a minimum of 6 months prior to study Prior or concomitant treatment with experimental drugs, high dose steroids, or any other cancer treatment within 4 weeks prior to the first dose of the study product Consumption of Muscadine Plus over the past 2 months Known allergy to muscadine grapes or ellagic acid Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Negative PSA doubling time (1 time point may be excluded per 3e inclusion criteria)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Arm 1: participants in dose-escalation phase (Phase 1) Arms 2-4: Randomized, double-blind (Phase 2); control, low-dose, high-dose
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Dose-escalation of Muscadine Plus Grape Skin Extract<br>Muscadine Plus Grape Skin Extract (MPX): Phase I Dose-escalation starts at 500mg daily for 1 cycle (28 days), then increased to 1000mg for 2nd cycle, then increased to 2000mg daily for 3rd cycle, then increased to 3000mg daily for 4th cycle, then increased to maximum dose of 4000mg daily for final cycle. Pills given by mouth once daily for 28 days per cycle. | Drug: Muscadine Plus Grape Skin Extract<br>* Phase I: Dose escalation starts at 500mg pills given by mouth once daily for 28 days per cycle<br>|
| Placebo Comparator: Phase 2: Placebo control<br>Randomly-assigned participants receive 8 capsules once daily of placebo composed of pulverized rice for up to 12 cycles (28 days per cycle). | Drug: Placebo oral capsule<br>* Randomly-assigned participants receive 8 capsules once daily of placebo composed of pulverized rice for up to 12 cycles (28 days per cycle).<br>|
| Experimental: Phase 2: Low-dose MPX<br>Randomly-assigned participants receive low-dose (500mg) MPX | Drug: Low-dose MPX<br>* Randomly-assigned participants receive one capsule of drug (500mg MPX) and seven capsules of placebo composed of pulverized rice, once daily for up to 12 cycles (28 days per cycle).<br>|
| Experimental: Phase 2: High-dose MPX<br>Randomly-assigned participants receive high-dose (4000mg) MPX | Drug: High-dose MPX<br>* Randomly-assigned participants receive 8 capsules of drug (4000mg MPX) once daily for up to 12 cycles (28 days per cycle).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (Phase I) Maximum Tolerated Dose | To determine the recommended dosing for Muscadine Plus and to evaluate the safety and tolerability of Muscadine Plus in prostate cancer patients with rising PSA following definitive therapy. | Up to 7 months post-intervention | 
| (Phase II) Prostate Specific Antigen Doubling Time (PSADT) | To define the effects of placebo and two different daily doses of MPX on PSADT in men who have rising PSA after initial definitive therapy for localized prostate cancer. | Change from baseline to month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | Adverse events reported verbally by patient and documented in study notes. | At month 12 post-intervention | 
| (Phase II) Proportion of Men Whose PSADT Increases Greater Than 33% |  | At month 12 post-intervention | 
| (Phase II) Number of Men With Greater Than 50% Reduction in PSA Compared to Baseline | Change in PSA values drawn over study period, taken every 3 months. PSA is measured in ng/mL | At month 12 post-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rising psa