Study of Metformin Plus Oligomeric Procyanidin Complex for Pharmacologic Manipulation of AGE (Advanced Glycation Endproducts) Levels in Prostate Cancer Patients

AGEs (advanced glycation endpoints) are a type of metabolite, or substance, found in the
food. The AGE content in food is determined by the types of food you eat and also how you
prepare your food. The researchers helping conduct this study have found a potential link
between AGE levels and cancer. The purpose of this study is to identify safe pharmaceutical
agents that can reduce the AGE levels in subjects with advanced cancer.

Inclusion Criteria:

1. Confirmation of adenocarcinoma of the prostate that is documented by one of the
following: pathology report or clinic note with documented history of prostate cancer.

2. Subjects must be receiving ADT with a GnRH agonist or antagonist, with or without an
anti-androgen, with a current testosterone level documented to be <50ng/dL at
enrollment. Subjects whose ADT is interrupted may enroll or continue on study as long
as the testosterone is documented to remain <50ng/dL for the entire duration of study
participation. Subjects who have undergone orchiectomy are also eligible.

3. Subjects must have adequate hematologic, renal, and hepatic function at baseline, as
follows:

- Hematology parameters: ANC >1000/mcL, platelets > 100,000/mcL, Hgb >8.0gm/dL

- Renal Function: eGFR of ≥ 45mls/min using Cockkroft and Gault formula (see
appendix C).

- Liver Function: Total bilirubin ≤ULN, AST and ALT <1.5xULN, Prior radiation
therapy allowed

4. Subjects may have diabetes mellitus but must not be taking metformin.

5. Able to swallow and retain oral medication

6. ECOG performance status of 0 - 2

7. Ability to sign written informed consent

8. Testosterone level <50ng/dL at time of enrollment.

9. Age 18 or older.

Exclusion Criteria:

1. Known allergy to grapes or grape seed

2. Known hypersensitivity or intolerance to metformin.

3. Any condition associated with increased risk of metformin-associated lactic acidosis
(e.g. congestive heart failure defined as NYHA Class III or IV functional status,
history of acidosis of any type; habitual intake of 3 or more alcoholic beverages per
day).

4. Prior cytotoxic chemotherapy for metastatic prostate cancer; prior treatment with
genomically-targeted agents, or Provenge is allowed.

5. History of receiving more than 2 classes of ADT.

6. Current use of metformin, or strong antioxidants (extracts from grape seed, milk
thistle; pine bark, green tea, saw palmetto; resveratrol; flavonoids; catechins;
ellagic acid), large quantities of red grapes, white button mushrooms, red wine

7. PSA doubling time of <6 months, measured over the 3 months prior to enrollment.