Muscadine Plus in Treating Rising PSA Levels in Men Carrying a Specific Gene Variant (Alanine / Alanine SOD2 Genotype) Following Initial Therapy for Prostate Cancer
- Subject has histologically or cytologically confirmed adenocarcinoma of the prostate
- Subject has undergone definitive treatment (surgery, surgery with radiation therapy, cryotherapy, radiation therapy or brachytherapy) for the primary prostate tumor * 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
- 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). The three time points must be at least 21 days apart. Note: Fluctuations in PSA are allowed per Bubley et al 1999 working group criteria.
- For purposes of calculating PSADT: * All PSA values used in the calculation should be >= 0.10 ng/ml and overall should follow a rising trend; * Record every available PSA drawn within the last 12 months; * The minimum requirement is 3 PSA values; * For radiotherapy only patients, record PSA nadir value and collection date PSADT must be positive according to Memorial Sloan Kettering Cancer Center Prostate Cancer Nomograms.
- At least 2 PSA rises need to be after a normal testosterone for those patients who had prior hormone therapy
- One of the following criteria must be met. * Absolute level of PSA > 0.4 ng/mL following surgery (surgery only) * Absolute level of PSA > 0.4 ng/mL for subjects treated with multiple treatment modalities (e.g., surgery + radiation, surgery + cryotherapy, etc.) * 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)
- Subject has life expectancy of greater than 12 months
- Subject has Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
- Subject has testosterone level of >= 150 ng/dL at screening
- Leukocytes > 3,000/mcL
- Absolute neutrophil count > 1,500/mcL
- Platelets > 100,000/mcL
- Total bilirubin =< 1.5 x upper limit of normal except for Gilberts =< 2.5 x upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X upper limit of normal
- Creatinine =< 2.5 upper limit of normal
- Subject agrees to abstain from other commercially available MuscadinePlus (MP) products (Vinetra, MPlus or MP capsules) while participating in this study
- 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
- Subject has signed a written informed consent document and agrees to comply with requirements of the study
- Computed tomography (CT) or magnetic resonance imaging (MRI) chest/abdomen/pelvis and bone scan without evidence of metastatic disease as an inclusion (Chest X ray may be used instead of chest CT scan).
- Subject agrees to genotyping of MnSOD2 gene. Only those with AA genotype will be randomized
- 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 2.0 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 three months, per standard of care
- 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
- 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
- Subject has consumed any muscadine plus over the past 2 months
- Subject has a known allergy to muscadine grapes, ellagic acid or rice.
- 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
- Subject has negative PSA doubling time (negative doubling time corresponds with decreasing PSA) Doubling time may be computed using the Sloan Kettering prediction tools
District of Columbia
I. To determine if men with rising PSA after initial therapy for localized prostate cancer who display the alanine/alanine (AA) genotype of manganese superoxide dismutase (MnSOD) and supplement their diet with muscadine plus (MPX) have greater decrease in PSA slope following treatment compared to men that do not supplement with MPX.
I. To estimate the prostate specific antigen doubling time (PSADT) of the two treatment groups.
II. To estimate the fraction of patients with a decrease in PSA of >= 50% from the start of treatment (PSA objective response rate) at 24 and 48 weeks.
III. To estimate the time to disease progression for both treatment groups by PSA progression as well as by radiologic disease progression (i.e. development of metastatic disease).
I. To correlate baseline and change of levels of antioxidants (selenium, lycopene, and alpha-tocopheral) with changes in PSA.
II. To correlate measures of oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG], malondialdehyde and F2-isoprostanes) with PSA changes.
III. To store blood for future evaluation of biomarkers associated with MPX effect if the study is positive.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive muscadine plus orally (PO) once daily (QD). Cycles repeat every 12 weeks (84 days) for up to 48 weeks in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive placebo PO QD. Cycles repeat every 12 weeks (84 days) for up to 48 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 28 days.
Trial Phase Phase III
Trial Type Treatment
Johns Hopkins University / Sidney Kimmel Cancer Center
Channing J. Paller
- Primary ID J1823
- Secondary IDs NCI-2018-02957, CRMS-68615, IRB00166021
- Clinicaltrials.gov ID NCT03535675