Effects of Muscadine Grape Extract in Men With Biochemically Recurrent Prostate Cancer on Androgen Deprivation Therapy

Diet supplementation for the prevention or treatment of cancer is attractive, as
implementation is relatively easy, even in populations with reduced incomes and resources.
Grape extracts or active components isolated from grapes have received attention as
chemopreventive or therapeutic agents based upon their anti-proliferative, anti-inflammatory,
and anti-oxidant properties. The muscadine grape contains a high concentration of anthocyanin
3,5-diglucosides, ellagic acid, ellagic acid precursors, gallic acid, flavan-3-ols and
flavonols. Several preclinical studies with muscadine grape products have revealed anti-tumor
activity, including inhibition of tumor cell growth and induction of apoptosis. By reducing
levels of circulating inflammatory markers such as CRP and IL-6, muscadine grape products may
improve cancer outcomes by decreasing symptom burden, particularly fatigue. Despite reports
indicating potential anti-tumor activity, there are limited clinical studies on the efficacy
of muscadine grape products in the prevention or treatment of cancer or cancer-related side
effects, representing an opportunity for novel investigation. The primary goal will be to
determine whether treatment with MGE can improve measures of fatigue in men with
biochemically recurrent prostate cancer on androgen deprivation therapy (ADT).

Inclusion Criteria:

- Men age ≥18 years.

- Histologically confirmed prostate adenocarcinoma.

- Definitive therapy of primary prostate tumor completed. Definitive therapy can be
prostatectomy, primary radiation therapy, brachytherapy, or cryotherapy. Salvage
radiation after prostatectomy is allowed, if completed >30 days prior to study entry.

- PSA greater than 0.2 ng/mL and rising on a minimum of 2 time points prior to ADT
initiation. All PSA measurements must be at least 7 days apart.

- Normal organ and marrow function as defined below:

White blood cell count >3,500/mcL Platelet count >75,000/mcL Hemoglobin >9 g/dL Total
bilirubin <2.5 X institutional upper limit of normal AST(SGOT)/ALT(SGPT) <2.5 X
institutional upper limit of normal Creatinine <2.5 X institutional upper limit of normal

- Androgen deprivation therapy (ADT) starting <60 days prior. Prior ADT in the setting
of radiation therapy permitted, as long as testosterone recovered to >100 before
restarting ADT.

- Able to ambulate (use of assist device is acceptable).

- Able to cooperate with study-related activities.

- The effects of MGE on the developing human fetus are unknown. Men must agree to use
adequate contraception (barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation.

- Ability to understand and the willingness to sign an IRB-approved informed consent
document (either directly or via a legally authorized representative).

Exclusion Criteria:

- Symptomatic metastatic disease. Pelvic or retroperitoneal nodes <2 cm allowed; 3 or
fewer bone metastasis allowed, provided they are asymptomatic.

- Any cancer treatment other than ADT within 30 days prior to study entry.

- Ongoing use of any other investigational cancer-directed agents.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to MGE.

- Inability to swallow oral medications.

- Malabsorption due to bowel resection or gastrointestinal disease leading to
uncontrolled diarrhea, or persistent nausea or vomiting requiring daily antiemetic
therapy for symptom management within the past week.

- 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.