Clinical Trials /

Muscadine Plus (MPX) In Men With Prostate Cancer

NCT03535675

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Muscadine Plus (MPX) In Men With Prostate Cancer
  • Official Title: A Randomized Double-Blind, Placebo-Controlled Study Of The Effects Of MPX Capsules On Rising Prostate-Specific Antigen Levels In Alanine/Alanine SOD2 Genotype Men Following Initial Therapy For Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: J1823
  • SECONDARY ID: IRB00166021
  • NCT ID: NCT03535675

Conditions

  • Adenocarcinoma of the Prostate

Interventions

DrugSynonymsArms
Muscadine PlusMPXMuscadine Plus
PlacebosPlaceboPlacebo

Purpose

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.

Detailed Description

      Prostate specific antigen (PSA) is a single-chain glycoprotein produced by the epithelial
      cells of the prostate. PSA has been used for early detection and monitoring of patients with
      prostate cancer who receive a variety of treatments. Due to the widespread use of serum PSA
      to monitor for prostate cancer recurrence following primary treatment, there exists a group
      of men with a rising PSA as their only evidence of recurrence. These patients may not
      demonstrate clinical or radiographic evidence of disease progression for an average 8 years
      from the time of detectable PSA to detectable metastatic disease by standard imaging.
      Currently there are limited treatment options for these patients that may delay disease
      progression or improve survival, including salvage radiation for prior surgical patients,
      hormonal therapy, and active surveillance.

      Although some surgical patients are candidates for salvage radiation, not all patients will
      want salvage radiation. Even the early initiation of hormonal therapy (e.g., luteinizing
      hormone releasing hormone (LHRH) analogs) has not demonstrated a survival benefit, although
      Schroder et al suggests an advantage for early hormone therapy in the setting of metastatic
      regional lymph nodes. Furthermore, early initiation of androgen ablation is associated with
      significant morbidity and impact on quality of life, including fatigue, hot flashes, loss of
      libido, decreased muscle mass, and osteoporosis with long term use. This group of relatively
      well men with biochemical recurrence are currently offered androgen ablation therapy or
      active surveillance (regular PSA monitoring and annual scans) until there is evidence of
      metastatic disease, because other options have not been available. These patients are
      excellent candidates for innovative treatments hypothesized to slow the progression of
      clinical prostate cancer and delay the development of metastatic disease.

      As the previous section documents, preclinical studies of muscadine grape skin offer evidence
      that it may extend the time between biochemical recurrence and development of metastatic
      disease. While the Phase II study described above found no significant difference in PSA
      doubling time between placebo and either dose of MPX, there was a signal of benefit in the
      subgroup analysis of men with the Alanine/Alanine superoxide dismutase 2 (SOD2) genotype that
      received high dose MPX. It is therefore proposed to test the benefits of high dose MPX in
      capsule formulation in a randomized, controlled study of men who have failed primary therapy,
      either radiation, surgery or cryotherapy, as primary treatment for prostate cancer. Eligible
      subjects will have a rising PSA and will have 3 PSA values at least 7 days apart with a
      recovered testosterone to be able to calculate a baseline PSA doubling time. The primary
      endpoint of this study will be mean PSA slope during the study period.
    

Trial Arms

NameTypeDescriptionInterventions
Muscadine PlusExperimentalEach 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.
  • Muscadine Plus
PlaceboExperimentalEach 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.
  • Placebos

Eligibility Criteria

        Inclusion Criteria:

        Patients meeting the following conditions are eligible for registration and participation
        in the study:

          1. Subject has histologically or cytologically confirmed adenocarcinoma of the prostate

          2. Subject has undergone definitive treatment (surgery, surgery with radiation therapy,
             cryotherapy, radiation therapy or brachytherapy) for the primary prostate tumor.

             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.

          3. 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 PSADT:

               1. All PSA values used in the calculation should be ≥ 0.20 ng/ml and overall should
                  follow a rising trend;

               2. Record every available PSA drawn within the last 12 months of the most recent
                  local PSA;

               3. The minimum requirement is 3 PSA values obtained over 3 months with a minimum of
                  4 weeks between measurements;

               4. 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;

               5. 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 under this link:
                  http://www.mskcc.org/applications/nomograms/prostate/PsaDoublingTime.aspx

          4. One of the following criteria must be met.

               1. Absolute level of PSA >0.4 ng/mL following surgery. (surgery only)

               2. Absolute level of PSA >0.4 ng/mL for subjects treated with multiple treatment
                  modalities (e.g., surgery + radiation, surgery + cryotherapy, etc.).

               3. 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)

          5. Subject is >18 years of age.

          6. Subject has life expectancy of greater than 12 months.

          7. Subject has Eastern Cooperative Oncology Group performance status 0, 1 or 2

          8. Subject has testosterone level of ≥1.5 ng/mL at screening.

          9. Subject has normal organ and marrow function as defined below:

               1. Leukocytes >3,000/microliter

               2. absolute neutrophil count >1,500/microliter

               3. platelets >100,000/microliter

               4. total bilirubin <1.5 x upper limit of normal except for Gilberts <2.5 x upper
                  limit of normal

               5. aspartate aminotransferase/Alanine transaminase ≤ 2.5 X upper limit of normal

               6. creatinine ≤ 2.5 upper limit of normal

         10. Subject agrees to abstain from other commercially available MuscadinePlus (MP)
             products (Vinetra, MuscadinePlus or MP capsules) while participating in this study.

         11. 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.

         12. Subject has signed a written informed consent document and agrees to comply with
             requirements of the study.

         13. CT or MRI chest/abdomen/pelvis and bone scan without evidence of metastatic disease as
             an inclusion.

         14. Subject agrees to genotyping of manganese-dependent superoxide dismutase 2 (MnSOD2)
             gene and any genetic counseling. Only those with Alanine/Alanine SOD2 genotype will be
             randomized.

        Exclusion Criteria:

        Subjects meeting the following conditions are not eligible for participation in the study:

          1. 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 four months, per standard of
             care.

          2. 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.

          3. 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.

          4. Subject has consumed any Muscadine Plus over the past 2 months.

          5. Subject has a known allergy to muscadine grapes, ellagic acid or rice

          6. 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.

          7. 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
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Prostate specific antigen (PSA) response
Time Frame:2 years
Safety Issue:
Description:To determine if men who display the Alanine/Alanine 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 increase/decrease of serum PSA in ng/mL, according to the level of prostate-specific antigen lab values, using the consensus guidelines of the Prostate Cancer Clinical Trials Working Group 2 criteria.

Secondary Outcome Measures

Measure:PSA doubling time
Time Frame:1 year
Safety Issue:
Description:PSA doubling time (PSADT) will be calculated in months by measuring the PSA values within 12 months from start of intervention.
Measure:PSA objective response rate
Time Frame:1 year
Safety Issue:
Description:The fraction of patients with a decrease in PSA of ≥50% from the start of intervention at 24 and 48 weeks.
Measure:PSA Progression
Time Frame:2 years
Safety Issue:
Description:The time to disease progression for both treatment groups by PSA progression.
Measure:Radiographic Progression
Time Frame:2 years
Safety Issue:
Description:The time to disease progression for both treatment groups by radiologic disease progression (i.e. development of metastatic disease).

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Last Updated

August 13, 2019