Aborption and Metabolism of Lyophilized Black Raspberry Food Products in Men With Prostate Cancer Undergoing Surgery

PRIMARY OBJECTIVES:

I. To conduct a dose-escalation study to determine safety and compliance of varying
lyophilized black raspberry (LBR) delivery vehicles (a gummy confection and a nectar) at two
different doses.

SECONDARY OBJECTIVES:

I. To precisely quantify changes in the content and distribution of black raspberry
phytochemicals and their metabolites in the blood and urine and correlate these
concentrations with prostate tissue phytochemicals.

II. Measure the ability of black raspberry gummy confection and nectar in altering hormonal
patterns (lower insulin-like growth factor-1 [IGF-I], higher insulin-like growth
factor-binding protein 3 [IGF-BP3], lower androgens) consistent with reduced prostate
carcinogenesis and in parallel with an enhanced capacity to quench reactive oxygen.

III. Investigate histopathologic, immunologic, and molecular biomarkers associated with
prostate carcinogenesis that may serve as surrogate endpoint biomarkers and provide
information regarding their ability to be modulated by black raspberries.

IV. Determine if consumption of black raspberries alters molecular markers in the human
prostate including: (a) neuroendocrine markers such as IGF-I and IGF-BP3, (b) signal
transduction markers such as phosphatase and tensin homologue (PTEN) and phospho-AKT, and (c)
angiogenesis regulators such as (vascular epithelial growth factor (VEGF).

V. Collect and store plasma and peripheral blood mononuclear cells (PBMCs) from each patient
to assess systemic markers of inflammation and immune response.

OUTLINE: This is a dose-escalation study of lyophilized black raspberry gummy confection and
nectar. Patients are assigned to 1 of 7 treatment arms.

ARM I: Patients follow a regular diet for 4-6 weeks and then undergo prostatectomy.

ARM II: Patients follow a low polyphenol diet for 4-6 weeks and then undergo prostatectomy.

ARM III: Patients follow a low ellagitannin diet for 4-6 weeks and then undergo
prostatectomy.

ARM IV: Patients follow a low ellagitannin diet and receive lower-dose black raspberry gummy
orally (PO) daily for 4-6 weeks and then undergo prostatectomy.

ARM V: Patients follow a low ellagitannin diet and receive higher-dose black raspberry gummy
PO daily for 4-6 weeks and then undergo prostatectomy.

ARM VI: Patients follow a low ellagitannin diet and receive lower-dose black raspberry nectar
PO daily for 4-6 weeks and then undergo prostatectomy.

ARM VII: Patients follow a low ellagitannin diet and receive higher-dose black raspberry
nectar PO daily for 4-6 weeks and then undergo prostatectomy.

Inclusion Criteria:

- Have biopsy proven carcinoma of the prostate

- Have chosen a radical prostatectomy for treatment of their disease after the medical
team has presented all possible treatment options

- Not be receiving neoadjuvant hormonal or chemotherapy (other clinical trials)

- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

- Not currently taking berry dietary supplements, or "alternative" products (Acai berry,
pomegranate, black raspberry, Optiberry, Juice Plus)

- Have BUN/Cr (blood urea nitrogen and serum creatinine) within normal limits

- Have liver enzymes within normal limits

- Have complete blood count (CBC) within normal limits

- Have prothrombin time/partial thromboplastin time (PT/PTT/INR) within normal limits

- Voluntarily agree to participate and sign an informed consent document

- Agree to have prostate biopsy blocks provided to the study for evaluation

- Agree to consume a standardized vitamin and mineral supplement and avoid other
nutrition, dietary, or alternative medications/supplements for the duration of the
study

- Agree to follow a controlled polyphenolic and/ or ellagitannin diet

Exclusion Criteria:

- Have an active malignancy other than prostate cancer that requires therapy

- Have a prostate biopsy with less than 5% cancer involvement

- Have a history of traumatic or surgical castration

- Have a history of pituitary hormone diseases that currently require supplemental
hormonal administration (thyroid hormones, adrenocorticotropic hormone [ACTH], growth
hormone) or other endocrine disorders requiring hormone administration with the
exception of diabetes and osteoporosis

- Are taking certain medications; no concurrent finasteride (Proscar) or other hormonal
agents for chemoprevention/treatment of benign prostate hyperplasia (BPH); utilizing
prescription medications for urinary outlet obstructive symptoms will not be
permitted; the use of non-prescription substances to improve urinary tract symptoms
will not be permitted (i.e. Saw Palmetto, other herbal, alternative products)

- Have a known allergy to black raspberries, corn, and wheat products or those who have
never consumed any of these products

- Have active metabolic or digestive illnesses such as malabsorptive disorders (Crohn's,
Celiac disease, irritable bowel syndrome [IBS]), renal insufficiency, hepatic
insufficiency, cachexia, or short bowel syndrome

- Have significant loss of gastrointestinal organs due to surgery, except for appendix

- Have altered immunity such as autoimmune disorders, cancer, anemia, hemophilia, and
blood dyscrasias

- Have noticeable open lesions in the oral cavity, sores that have not healed for more
than 2 months or have a history of leukoplakia, tumors of the buccal cavity, throat,
and lips

- Have difficulty swallowing (dysphagia), pain with swallowing (odynophagia), salivary
gland dysfunction, or xerostomia (dry mouth)

- Are taking medications that inhibit clotting (warfarin sodium) or using prescribed
oral rinses (Peridex)