Muscadine Plus (MPX) In Men With Prostate Cancer

NCT03535675 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: J1823IRB00166021
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 13

Brief Summary

This research is being done to determine if men with rising PSA after initial therapy for localized prostate cancer who display the Alanine/Alanine SOD2 genotype of MnSOD and supplement their diet with MPX have greater decrease in PSA slope following treatment compared to men that do not supplement with MPX.

Conditions

Adenocarcinoma of the Prostate

Outcome Measures

Primary Outcomes (1)

• Prostate Specific Antigen (PSA) Response

  To determine if men who display the Alanine/Alanine superoxide dismutase 2 (SOD2) genotype of MnSOD and supplement their diet with MPX have greater changes in PSA slope following treatment compared to men that do not supplement with MPX. PSA response will be measured as the change of serum PSA in ng/mL/month, on-study PSA slope for each patient with comparisons between treatment arms adjusted for pre-study PSA slope; on-study PSA slope was calculated from PSA values taken at baseline,12, 24, 36, and 48 weeks, and calculated as the slope of the simple linear regression of the natural log of PSA versus time in ng/mL/month.

  baseline,12, 24, 36, and 48 weeks

Secondary Outcomes (4)

• PSA Doubling Time

  Up to 26 months

• PSA Objective Response Rate

  Up to 1 year

• PSA Progression

  2 years

• Radiographic Progression

  2 years

Study Arms (2)

Muscadine Plus

EXPERIMENTAL

Each treatment cycle consists of once daily oral dosing of 4000 mg Muscadine Plus, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of study drug and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug.

Drug: Muscadine Plus

Placebo

EXPERIMENTAL

Each treatment cycle consists of once daily oral dosing of 4000 mg placebos, every day throughout each 12 week (84 day) cycle. Patients may continue to receive additional cycles of placebo and will be followed every three months with standard visits with their physician until completion of 48 weeks of study treatment, disease progression, or until they wish to discontinue the drug.

Drug: Placebos

Interventions

Muscadine Plus DRUG

Ellagic acid inhibits DNA Methyltransferase. DNA Methyltransferases (DNMTs) are a family of enzymes that regulate chromatin methylation and use S-adenosyl methionine (SAM) as the methyl donor. Ellagic acid's metabolite, urolithin-A inhibits the protein complex nuclear factor kappa-light-enhancer of activated B-cells (NFkB), potentially leading to increased rates of apoptosis and decreases in cancer cell proliferation. Extracts from Vitis rotundifolia have shown inhibition of the phosphatidylinositol 3-kinase-Akt pathway.

Also known as: MPX

Muscadine Plus

Placebos DRUG

The placebo capsules are rice flour that will be placed in white opaque capsules identical to the ones used for MPX.

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients meeting the following conditions are eligible for registration and participation in the study:
• 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 (prior chemotherapy is not allowed) .
• a. 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).
• For purposes of calculating PSA doubling time (PSADT):
• All PSA values used in the calculation should be ≥ 0.20 ng/ml and overall should follow a rising trend;
• Record every available PSA drawn within the last 12 months of the most recent local PSA;
• The minimum requirement is 3 PSA values obtained over 3 months with a minimum of 4 weeks between measurements;
• If there are 4 or more PSAs available, the time interval between the first and last PSA measurements must be at least 3 months, and, there is no minimum time interval requirement between any two PSA measurements;
• For radiotherapy only patients, record PSA nadir value and collection date. PSADT (PSA doubling time) must be positive according to Memorial Sloan Kettering Cancer Center Prostate Cancer Nomograms under this link: http://www.mskcc.org/applications/nomograms/prostate/PsaDoublingTime.aspx
• 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)

You may not qualify if:

• Subjects meeting the following conditions are not eligible for participation in the study:
• 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 1.5 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 four 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 posted at http://www.mskcc.org/applications/nomograms/prostate/PsaDoublingTime.aspx

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Greater Washington Community Foundation: collaborator

Study Sites (13)

City of Hope

Duarte, California, 91010, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Allegheny Health Network

Pittsburgh, Pennsylvania, 15212, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• Mandl A, Zahurak ML, Metri NA, Shore ND, Mao S, McKay RR, Taplin ME, Szmulewitz RZ, Maughan BL, Reichert ZR, Kessler ER, Heath EI, Dreicer R, Stein CA, Milne GL, Sfanos KS, Ernst SE, Mummert LA, Cruz-Lebron A, Michel SLJ, Kane MA, Hursey M, Worth MA, Wagner WD, Eshleman JR, Debeljak M, Xu L, Cao H, Dowling D, Marshall CH, Markowski MC, Denmeade SR, Eisenberger MA, Antonarakis ES, Carducci MA, Paller CJ. Muscadine Grape Skin Extract in Biochemically Recurrent Prostate Cancer: A Randomized, Placebo-Controlled, Biomarker-Enriched Trial in Patients With the SOD2 Ala/Ala Variant. Prostate. 2025 Jul;85(10):966-976. doi: 10.1002/pros.24903. Epub 2025 May 5.

  PMID: 40325900 DERIVED

Results Point of Contact

• Title: Channing Paller; M.D.
• Organization: Johns Hopkins University

cpaller1@jhmi.edu

4109558239

Study Officials

• Channing Paller, M.D

  SKCCC at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter, double-blind, randomized study to evaluate the benefit of MPX supplementation in the subset of men who display the Alanine/Alanine SOD2 genotype of MnSOD. Based on a previous randomized phase II trial of MPX at Hopkins, PSA doubling time (PSA-DT) was prolonged in this subgroup of men.

Study Record Dates

• First Submitted: May 10, 2018
• First Posted: May 24, 2018
• Study Start: October 30, 2018
• Primary Completion: July 6, 2022
• Study Completion: November 3, 2022
• Last Updated: May 22, 2023
• Results First Posted: May 22, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)