Muscadine Plus (MPX) In Men With Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT03535675|
Recruitment Status : Recruiting
First Posted : May 24, 2018
Last Update Posted : November 22, 2018
|Condition or disease||Intervention/treatment||Phase|
|Adenocarcinoma of the Prostate||Drug: Muscadine Plus Drug: Placebos||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||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.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Actual Study Start Date :||October 30, 2018|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2021|
Experimental: Muscadine Plus
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
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 phosphatidylinsoitol 3-kinase-Akt pathway.
Other Name: MPX
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.
The placebo capsules are rice flour that will be placed in white opaque capsules identical to the ones used for MPX.
Other Name: Placebo
- Prostate specific antigen (PSA) response [ Time Frame: 2 years ]
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.
- PSA doubling time [ Time Frame: 1 year ]PSA doubling time (PSADT) will be calculated in months by measuring the PSA values within 12 months from start of intervention.
- PSA objective response rate [ Time Frame: 1 year ]The fraction of patients with a decrease in PSA of ≥50% from the start of intervention at 24 and 48 weeks.
- PSA Progression [ Time Frame: 2 years ]The time to disease progression for both treatment groups by PSA progression.
- Radiographic Progression [ Time Frame: 2 years ]The time to disease progression for both treatment groups by radiologic disease progression (i.e. development of metastatic disease).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03535675
|Contact: Donnie Dowling, RNemail@example.com|
|Contact: Rana Sullivan, RNfirstname.lastname@example.org|
|United States, District of Columbia|
|Sibley Memorial Hospital||Recruiting|
|Washington, District of Columbia, United States, 20016|
|Contact: Channing Paller, MD 202-660-6500 email@example.com|
|United States, Maryland|
|Johns Hopkins Hospital||Recruiting|
|Baltimore, Maryland, United States, 21205|
|Contact: Donna Dowling, RN 410-614-9526 firstname.lastname@example.org|
|Principal Investigator: Channing Paller, MD|
|Principal Investigator:||Channing Paller, M.D||SKCCC at Johns Hopkins|