Prostate Cancer
Conditions
Keywords
Rising psa
Brief summary
This research is being done to test an investigational product called Muscadine Plus in the treatment of men who have received initial therapy (surgery and or radiation, cryotherapy or brachytherapy) for prostate cancer and are experiencing a rise in their prostate-specific antigens (PSA) level.
Detailed description
In phase I the investigators are evaluating the safety of the product and checking blood levels of the active components. In phase II the investigators are evaluating the effect of MPX on PSA doubling time
Interventions
DRUGMuscadine Plus Grape Skin Extract
Phase I: Dose escalation starts at 500mg pills given by mouth once daily for 28 days per cycle
DRUGLow-dose MPX
Randomly-assigned participants receive one capsule of drug (500mg MPX) and seven capsules of placebo composed of pulverized rice, once daily for up to 12 cycles (28 days per cycle).
DRUGHigh-dose MPX
Randomly-assigned participants receive 8 capsules of drug (4000mg MPX) once daily for up to 12 cycles (28 days per cycle).
DRUGPlacebo oral capsule
Randomly-assigned participants receive 8 capsules once daily of placebo composed of pulverized rice for up to 12 cycles (28 days per cycle).
Sponsors
Howard University
Prostate Cancer Clinical Trials Consortium
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Phase 1 (Arms 1) - open label Phase 2 (Arms 2-4) - randomized, double-blind
Intervention model description
Arm 1: participants in dose-escalation phase (Phase 1) Arms 2-4: Randomized, double-blind (Phase 2); control, low-dose, high-dose
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the prostate. * Undergone definitive treatment (surgery, surgery with radiation therapy, cryotherapy, radiation therapy or brachytherapy) for the primary prostate tumor. * Rising PSA on a minimum of 3 time points (including screening psa) within the 12 months prior to study initiation. * \> 18 years of age. * Life expectancy of greater than 6 months. * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2. * Testosterone level of ≥1.5 ng/mL at screening. * Adequate kidney, liver and bone marrow function * Agrees to abstain from other commercially available MP products while participating in this study. * Subject's use of other dietary/herbal supplements (e.g. saw palmetto, selenium, 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. * Signed a written informed consent document and agrees to comply with requirements of the study.
Exclusion criteria
* 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 * Receipt of any therapies that modulate testosterone levels (e.g., androgen ablative/anti-androgen therapy, 5 alpha reductase inhibitors) for a minimum of 6 months prior to study * 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 * Consumption of Muscadine Plus over the past 2 months * Known allergy to muscadine grapes or ellagic acid * Uncontrolled intercurrent 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 * Negative PSA doubling time (1 time point may be excluded per 3e inclusion criteria)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| (Phase I) Maximum Tolerated Dose | Up to 7 months post-intervention | To determine the recommended dosing for Muscadine Plus and to evaluate the safety and tolerability of Muscadine Plus in prostate cancer patients with rising PSA following definitive therapy. |
| (Phase II) Prostate Specific Antigen Doubling Time (PSADT) | Change from baseline to month 12 | To define the effects of placebo and two different daily doses of MPX on PSADT in men who have rising PSA after initial definitive therapy for localized prostate cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Tolerability | At month 12 post-intervention | Adverse events reported verbally by patient and documented in study notes. |
| (Phase II) Proportion of Men Whose PSADT Increases Greater Than 33% | At month 12 post-intervention | — |
| (Phase II) Number of Men With Greater Than 50% Reduction in PSA Compared to Baseline | At month 12 post-intervention | Change in PSA values drawn over study period, taken every 3 months. PSA is measured in ng/mL |
Countries
United States
Participant flow
Recruitment details
Recruitment dates: Phase I: October 4, 2011-August 7, 2012 in medical clinics Phase II: January 31, 2013-October 20, 2014
Pre-assignment details
Enrolled subjects agreed to abstain from other commercially available Muscadine Plus products while in this trial. If subjects were taking other dietary/herbal supplements (e.g. saw palmetto, selenium, pomegranate juice or pills, etc) prior to study entry, they had to be on a stable dose for 2 months prior and not stop while on trial.
Participants by arm
| Arm | Count |
|---|---|
| Dose-escalation Phase:Muscadine Plus Grape Skin Extract (MPX) Muscadine Plus Grape Skin Extract: Phase I Dose-escalation starts at 500mg daily for 1 cycle (28 days), then increased to 1000mg for 2nd cycle, then increased to 2000mg daily for 3rd cycle, then increased to 3000mg daily for 4th cycle, then increased to maximum dose of 4000mg daily for final cycle. Pills given by mouth once daily for 28 days per cycle. | 14 |
| Phase 2: Placebo Control Randomly-assigned participants receive 8 capsules once daily of placebo composed of pulverized rice for up to 12 cycles (28 days per cycle). | 24 |
| Phase 2: Low-dose MPX Randomly-assigned participants receive one capsule of drug (500mg MPX) and seven capsules of placebo composed of pulverized rice, once daily for up to 12 cycles (28 days per cycle). | 56 |
| Phase 2: High-dose MPX Randomly-assigned participants receive 8 capsules of drug (4000mg MPX) once daily for up to 12 cycles (28 days per cycle). | 49 |
| Total | 143 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Dose-escalation Phase 1 | Comorbidities, myasthenia gravis | 1 | 0 | 0 | 0 |
| Dose-escalation Phase 1 | Disease progression | 1 | 0 | 0 | 0 |
| Dose-escalation Phase 1 | Physician Decision | 5 | 0 | 0 | 0 |
| Randomized Phase 2 | Adverse Event | 0 | 0 | 0 | 1 |
| Randomized Phase 2 | Comorbidities | 0 | 2 | 2 | 2 |
| Randomized Phase 2 | Disease progression | 0 | 3 | 7 | 5 |
| Randomized Phase 2 | Disenrolled before treatment | 0 | 1 | 1 | 2 |
| Randomized Phase 2 | Patient stopped taking study drug | 0 | 0 | 0 | 1 |
| Randomized Phase 2 | Patient transferred to other facility | 0 | 0 | 1 | 0 |
| Randomized Phase 2 | Rising PSA, not as defined by protocol | 0 | 2 | 5 | 2 |
| Randomized Phase 2 | Withdrawal by Subject | 0 | 3 | 5 | 4 |
Baseline characteristics
| Characteristic | Phase 2: High-dose MPX | Phase 2: Placebo Control | Phase 2: Low-dose MPX | Total | Dose-escalation Phase:Muscadine Plus Grape Skin Extract (MPX) |
|---|---|---|---|---|---|
| Age, Continuous | 68 years STANDARD_DEVIATION 6.9 | 69 years STANDARD_DEVIATION 7.1 | 67 years STANDARD_DEVIATION 7.2 | 67.2 years STANDARD_DEVIATION 7.1 | 62.6 years STANDARD_DEVIATION 7.5 |
| Baseline PSA doubling time (PSADT) | — | — | — | 13 months STANDARD_DEVIATION 10.1 | 13 months STANDARD_DEVIATION 10.1 |
| Baseline PSADT ≤9 months | 27 Participants | 13 Participants | 32 Participants | 72 Participants | — |
| Baseline PSADT >9 months | 21 Participants | 10 Participants | 23 Participants | 54 Participants | — |
| Eastern Cooperative Oncology Group (ECOG) 0 | 39 Participants | 18 Participants | 52 Participants | 109 Participants | — |
| Eastern Cooperative Oncology Group (ECOG) 1 | 8 Participants | 5 Participants | 2 Participants | 15 Participants | — |
| Gleason score 6 | — | — | — | 3 Participants | 3 Participants |
| Gleason score ≤6, 3+4 | 23 Participants | 11 Participants | 25 Participants | 59 Participants | — |
| Gleason score 7 | — | — | — | 7 Participants | 7 Participants |
| Gleason score 8 | — | — | — | 1 Participants | 1 Participants |
| Gleason score ≥8, 4+3 | 26 Participants | 13 Participants | 31 Participants | 70 Participants | — |
| Gleason score 9 | — | — | — | 3 Participants | 3 Participants |
| Prior therapy Androgen Deprivation Therapy (ADT) | 19 Participants | 2 Participants | 25 Participants | 46 Participants | — |
| Prior therapy Brachytherapy | 3 Participants | 3 Participants | 5 Participants | 11 Participants | — |
| Prior therapy Cryotherapy | 1 Participants | 0 Participants | 49 Participants | 50 Participants | — |
| Prior therapy Radiation | 42 Participants | 21 Participants | 49 Participants | 116 Participants | 4 Participants |
| Prior therapy Radiation & Surgery | — | — | — | 9 Participants | 9 Participants |
| Prior therapy Surgery | 32 Participants | 16 Participants | 40 Participants | 89 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 6 Participants | 12 Participants | 32 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 18 Participants | 43 Participants | 109 Participants | 10 Participants |
| Region of Enrollment United States | 49 participants | 24 participants | 56 participants | 143 participants | 14 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 49 Participants | 24 Participants | 56 Participants | 143 Participants | 14 Participants |
| Superoxide dismutase 2 (SOD2) genotype Alanine/Alanine (Ala/Ala) | 10 Participants | 5 Participants | 12 Participants | 27 Participants | — |
| Superoxide dismutase 2 (SOD2) genotype Alanine/Valine (Ala/Val) | 22 Participants | 11 Participants | 21 Participants | 54 Participants | — |
| Superoxide dismutase 2 (SOD2) genotype Valine/Valine (Val/Val) | 5 Participants | 5 Participants | 11 Participants | 21 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 23 | 0 / 55 | 0 / 47 |
| other Total, other adverse events | 0 / 2 | 1 / 2 | 0 / 2 | 0 / 2 | 3 / 6 | 3 / 23 | 10 / 55 | 7 / 47 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 2 | 0 / 6 | 0 / 23 | 1 / 55 | 1 / 47 |
Outcome results
Primary
(Phase II) Prostate Specific Antigen Doubling Time (PSADT)
To define the effects of placebo and two different daily doses of MPX on PSADT in men who have rising PSA after initial definitive therapy for localized prostate cancer.
Time frame: Change from baseline to month 12
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose-escalation Phase:Muscadine Plus Grape Skin Extract (MPX) | (Phase II) Prostate Specific Antigen Doubling Time (PSADT) | 0.9 months |
| Phase 2: Placebo Control | (Phase II) Prostate Specific Antigen Doubling Time (PSADT) | 1.5 months |
| Phase 2: Low-dose MPX | (Phase II) Prostate Specific Antigen Doubling Time (PSADT) | 0.9 months |
Primary
(Phase I) Maximum Tolerated Dose
To determine the recommended dosing for Muscadine Plus and to evaluate the safety and tolerability of Muscadine Plus in prostate cancer patients with rising PSA following definitive therapy.
Time frame: Up to 7 months post-intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose-escalation Phase:Muscadine Plus Grape Skin Extract (MPX) | (Phase I) Maximum Tolerated Dose | 4000 mg |
Secondary
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Adverse events reported verbally by patient and documented in study notes.
Time frame: At month 12 post-intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose-escalation Phase:Muscadine Plus Grape Skin Extract (MPX) | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 7 Participants |
| Phase 2: Placebo Control | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 19 Participants |
| Phase 2: Low-dose MPX | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 38 Participants |
| Phase 2: High-dose MPX | Number of Participants With Adverse Events as a Measure of Safety and Tolerability | 32 Participants |
Secondary
(Phase II) Number of Men With Greater Than 50% Reduction in PSA Compared to Baseline
Change in PSA values drawn over study period, taken every 3 months. PSA is measured in ng/mL
Time frame: At month 12 post-intervention
Population: Patients counted in the analysis were evaluable if they completed at least six cycles of treatment prior to discontinuation
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose-escalation Phase:Muscadine Plus Grape Skin Extract (MPX) | (Phase II) Number of Men With Greater Than 50% Reduction in PSA Compared to Baseline | 0 Participants |
| Phase 2: Placebo Control | (Phase II) Number of Men With Greater Than 50% Reduction in PSA Compared to Baseline | 0 Participants |
| Phase 2: Low-dose MPX | (Phase II) Number of Men With Greater Than 50% Reduction in PSA Compared to Baseline | 1 Participants |
Secondary
(Phase II) Proportion of Men Whose PSADT Increases Greater Than 33%
Time frame: At month 12 post-intervention
Population: Data was not collected for this secondary outcome measure.