The MAP Trial: Phase III Study Of Muscadine Plus (MPX) In Men With Prostate Cancer: A Randomized Double-Blind, Placebo-Controlled Study Of The Effects Of MPX Capsules On Rising Prostate-Specific Antigen Levels In Alanine/Alanine SOD2 Genotype Men Following Initial Therapy For Prostate Cancer

This research is being done to determine if men with rising PSA after initial therapy for
localized prostate cancer who display the Alanine/Alanine SOD2 genotype of MnSOD and
supplement their diet with MPX have greater decrease in PSA slope following treatment
compared to men that do not supplement with MPX.

Inclusion Criteria:

Patients meeting the following conditions are eligible for registration and participation
in the study:

1. Subject has histologically or cytologically confirmed adenocarcinoma of the prostate

2. Subject has undergone definitive treatment (surgery, surgery with radiation therapy,
cryotherapy, radiation therapy or brachytherapy) for the primary prostate tumor (prior
chemotherapy is not allowed) .

a. A subject with a rising PSA post-prostatectomy should consider radiation as a
potentially curative alternative. If subject declines radiation or is not a candidate
for radiation, he may be considered eligible in this setting.

3. Subject has a rising PSA on a minimum of 3 time points (2 rises) within the 12 months
prior to study initiation (this will include the PSA measurement taken at the
screening visit, but not at the baseline day 0 study visit).

For purposes of calculating PSA doubling time (PSADT):

1. All PSA values used in the calculation should be ≥ 0.20 ng/ml and overall should
follow a rising trend;

2. Record every available PSA drawn within the last 12 months of the most recent
local PSA;

3. The minimum requirement is 3 PSA values obtained over 3 months with a minimum of
4 weeks between measurements;

4. If there are 4 or more PSAs available, the time interval between the first and
last PSA measurements must be at least 3 months, and, there is no minimum time
interval requirement between any two PSA measurements;

5. For radiotherapy only patients, record PSA nadir value and collection date. PSADT
(PSA doubling time) must be positive according to Memorial Sloan Kettering Cancer
Center Prostate Cancer Nomograms under this link:
http://www.mskcc.org/applications/nomograms/prostate/PsaDoublingTime.as…

4. One of the following criteria must be met.

1. Absolute level of PSA >0.4 ng/mL following surgery. (surgery only)

2. Absolute level of PSA >0.4 ng/mL for subjects treated with multiple treatment
modalities (e.g., surgery + radiation, surgery + cryotherapy, etc.).

3. A rise by 2 ng/mL or more above the nadir PSA will be considered the standard
definition for biochemical failure after radiation therapy with or without
hormonal therapy. (radiation only)

5. Subject is >18 years of age.

6. Subject has life expectancy of greater than 12 months.

7. Subject has Eastern Cooperative Oncology Group performance status 0, 1 or 2

8. Subject has testosterone level of ≥1.5 ng/mL at screening.

9. Subject has normal organ and marrow function as defined below:

1. Leukocytes >3,000/microliter

2. absolute neutrophil count >1,500/microliter

3. platelets >100,000/microliter

4. total bilirubin <1.5 x upper limit of normal except for Gilberts <2.5 x upper
limit of normal

5. aspartate aminotransferase/Alanine transaminase ≤ 2.5 X upper limit of normal

6. creatinine ≤ 2.5 upper limit of normal

10. Subject agrees to abstain from other commercially available MuscadinePlus (MP)
products (Vinetra, MuscadinePlus or MP capsules) while participating in this study.

11. Subject's use of other dietary/herbal supplements (e.g. saw palmetto, selenium,
pomegranate juice or pills, acai concentrated extract, 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.

12. Subject has signed a written informed consent document and agrees to comply with
requirements of the study.

13. CT or MRI chest/abdomen/pelvis and bone scan without evidence of metastatic disease as
an inclusion.

14. Subject agrees to genotyping of manganese-dependent superoxide dismutase 2 (MnSOD2)
gene and any genetic counseling. Only those with Alanine/Alanine SOD2 genotype will be
randomized.

Exclusion Criteria:

Subjects meeting the following conditions are not eligible for participation in the study:

1. Subject has known radiographic evidence of metastatic disease, except for presence of
positive lymph nodes from the surgical pathology. Pelvic/intraperitoneal lymph nodes
less than 1.5 cm maybe considered nonspecific and the patient would be eligible. If
there is any clinical suspicion for metastatic disease, CT and Bone Scan must be
performed to rule out metastatic disease, within the last four months, per standard of
care.

2. Subject has received any therapies that modulate testosterone levels (e.g., androgen
ablative/anti-androgen therapy, 5 alpha reductase inhibitors) for a minimum of 12
months prior to study.

3. Subject has had 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.

4. Subject has consumed any Muscadine Plus over the past 2 months.

5. Subject has a known allergy to muscadine grapes, ellagic acid or rice

6. Subject has uncontrolled concurrent 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.

7. Subject has negative PSA doubling time (negative doubling time corresponds with
decreasing PSA) Doubling time may be computed using the Sloan Kettering prediction
tools posted at
http://www.mskcc.org/applications/nomograms/prostate/PsaDoublingTime.as…