Patients will be randomized to muscadine grape extract (MGE). The patients will take 4 capsules by mouth BID (twice daily). Androgen deprivation therapy (ADT) is to be started within 60 days prior to initiation of MGE.

Patients will be randomized to placebo. The patients will take 4 capsules by mouth BID (twice daily). Androgen deprivation therapy (ADT) is to be started within 60 days prior to initiation of placebo.

Recurrent Prostate Cancer

The patients will take 4 capsules by mouth BID (twice daily).

Placebo

Androgen deprivation therapy (ADT) is to be started within 60 days prior to initiation of MGE.

WG Hefner VA Medical Center

Wake Forest Baptist Medical Center

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

A Phase 2 Double-blind, Placebo-controlled Study of the Effects of Muscadine Grape Extract in Men With Prostate Cancer on Androgen Deprivation Therapy

The PROMIS Fatigue 7a Short-Form assesses the experience (3 items) and impact (4 items) of fatigue. Item responses are rated on a five-point scale ranging from "never" to "always" and are summed for a total score and transformed to a T-score metric. Higher scores indicate more fatigue. Recommendations for classifying fatigue based on the T scores are as follows: <50 normal; 50-59 mild; 60-69 moderate; ≥70 severe.

General Quality of Life will be measured using the Patient Reported Outcomes Measurement Information System© (PROMIS©) Global Health Short Form (SF), a 10-item instrument representing multiple domains. Items assess self-reported measures of general aspects of physical, mental and social health in adults. Raw scores are summed within each sub-domain, and converted to T-scores. Higher scores indicate better general health than the general population.

Quality of life will be assessed by the Hot Flash Related Daily Interference Scale (HFRDIS). HFRDIS is a 10-item scale that assesses the degree to which hot flashes interfere with a variety of daily activities and quality of life. Interference is rated on an 11-point scale (0=not interfere; 10=completely interfere). Higher scores indicate more interference.

Sleep disturbance will be measured using the PROMIS Sleep Disturbance (SD) SF 8a. The PROMIS-SD items assess self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. Each question has five response options ranging in value from one to five. The lowest possible raw score is 8; the highest possible raw score is 40. Raw scores are converted to a standardized T-score. Higher scores indicate more sleep disturbance.

Cognitive abilities will be measured using the PROMIS Cognitive Abilities SF 4a, which assesses patient-perceived functional abilities related to mental acuity, concentration, and memory. Raw scores are converted to a standardized T-score; final scores are represented by the T-score. Higher scored indicate more cognitive ability.

Self-reported physical function will be measured using the PROMIS Physical Function 10a SF, which is designed to assess self-reported capability rather than actual performance of physical activities. The form consists of 10 items. Raw scores are summed within each sub-domain, and converted to T-scores. Higher scores indicate better physical function general health than the general population.

Physical performance will be objectively assessed using the Short Physical Performance Battery (SPPB). Each performance measure is scored ranging from 0-4 (0 = unable to complete; 4 = highest performance level), with total sum score range from 0-12. Lower score on the SPPB have been associated with increased risk of disability, hospitalization and worse survival among older adults with and without cancer.

Submaximal (6-minute walk) exercise capacity will be measured to assess physical fitness.

Whole body lean mass, fat mass, and bone mass will be measured by duel energy X-ray absorptiometry (DXA). BMI will be calculated from height and weight.

PSA will be measured at baseline, 6, and 12 months while patient is on MGE/placebo.

Progression-free survival is defined as the time from initiation of ADT treatment to disease progression or death.

Wake Forest University Health Sciences

This is a double-blind study. Only the lead-site investigational pharmacy team and the statistician will unblinded. The blind will be maintained until the study is complete.

Patients receive muscadine grape skin extract PO BID. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing benefit from muscadine grape skin extract may continue treatment in the absence of disease progression or unacceptable toxicity.

Patients receive muscadine grape skin extract PO BID. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing benefit from muscadine grape skin extract may continue treatment in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Muscadine Grape Skin Extract: Given PO
Quality-of-Life Assessment: Ancillary studies

Arm 1 (Muscadine Grape Skin Extract) 1 Pill Times a Day

Arm 2 (Muscadine Grape Skin Extract) 2 Pills Times a Day

Arm 3 (Muscadine Grape Skin Extract) 3 Pills Times a Day

Arm 4 (Muscadine Grape Skin Extract) 4 Pills Times a Day

Arm 5 (Muscadine Grape Skin Extract) 5 Pills Times a Day

Total

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Region of Enrollment

Maximum tolerable dose of muscadine grape extract is defined as the dose level immediately below the dose level that induced a dose-limiting toxicity (DLT) in >= 2 patients, as assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0DLT will be assessed by severity of adverse events.

Arm 1 (Muscadine Grape Skin Extract) 1 Pill 2 Times Per Day

Arm 2 (Muscadine Grape Skin Extract) 2 Pills 2 Times a Day

Arm 3 (Muscadine Grape Skin Extract) 3 Pills 2 Times a Day

Arm 4 (Muscadline Grape Skin Extract) 4 Pills 2 Times a Day

Arm 5 (Muscadine Grape Skin Extract) 5 Pills 2 Times a Day

Number of Participants With Dose-Limiting Toxicity

Pill count will be calculated from counting the number of pills returned as well as by summarizing the patient's pill diary. The percent of pills taken will be summarized by dose level using the mean and 95% confidence interval.

Adherence to MGE Treatment, as Measured by Percent of Pills Taken at the End of Every 4 Week Period

Best response will be characterized using a frequency table.

Best Response

A mixed model analysis of variance (ANOVA) model will be fit with phenolic level as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8.

Treatment (Muscadine Grape Skin Extract) FOR ALL ARMS

Change in Total Phenolic Levels in Blood

Change in Total Phenolic Levels in Urine

A mixed model ANOVA model will be fit with phenolic level as the outcome and time (baseline, every 4 weeks) as a fixed effect and subject as a random effect. Contrasts will be use to estimate changes from baseline to each follow-up time period.

Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by FACT-G

A mixed model ANOVA model will fit with the outcome of interest (cytokine or growth factor) as the outcome and time (baseline, 4, and 8 weeks) as a fixed effect and subject as a random effect. Contrasts will be used to estimate the changes from baseline to week 4 and week 8.

Change in Systemic Cytokine Levels

AEs/toxicity will be assessed at weeks 4, 8 and every 4 weeks thereafter if patients remain on treatment. Any expected toxicities, any laboratory based toxicities, and any grade 3 or higher gastrointestinal toxicities, and any grade 4 or higher toxicities will be summarized using frequency tables overall and by week.

Incidence of Adverse Events (AEs), Assessed Using NCI CTCAE Version 4.0

Response will be characterized using a frequency table.

Overall Response Rate of MGE (Complete Response, Partial Response, and Stable Disease)

OS will summarized using the Kaplan-Meier method. Median survival rates and associated 95% confidence intervals will be calculated.

Overall Survival (OS)

PFS will summarized using the Kaplan-Meier method.

Progression-free Survival (PFS)

Change in Component Phenolic Levels in Urine

Change in Component Phenolic Levels in Blood

Change in Quality of Life and Fatigue in Cancer Patients Taking MGE as Measured by PROMIS-Fatigue SF

Change in Systemic Cytokine Levels (Log IL-8)

Change in Systemic Cytokine Levels (Log VEGF)

Overall Study

Study Nurse

Patients receive muscadine grape skin extract PO BID. Treatment continues for 8 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing benefit from muscadine grape skin extract may continue treatment in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Muscadine Grape Skin Extract: Given PO

vitis rotundifolia/anticancer

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

Muscadine Grape Skin Extract in Treating Patients With Malignancy That Is Metastatic or Cannot Be Removed by Surgery

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