Prostate Cancer
Conditions
Keywords
Prostate Cancer, Radiation Therapy, Quality of Life, Symptom Management
Brief summary
The aim of this study is to test whether Saw Palmetto, is useful in preventing or reducing the side effects for men undergoing radiation therapy for prostate cancer. Urinary symptoms will be recorded each week, as well as assessment of quality of life through: 1) Physical Well-Being 2) Social/Family Well-being 3) Emotional Well-Being, and 4) Functional Well-Being.
Detailed description
Lower urinary tract symptoms (LUTS) affect from 75-80% of men undergoing radiation therapy (RT) for prostate cancer. The purpose of this study was to determine the feasibility, safety and efficacy of inexpensive, non-toxic herbal supplement, Saw Palmetto (SP), in treating these distressing symptoms. The study consisted of two phases: Dose Finding phase (DFP), and Exploratory Randomized Controlled Trail (RCT) phase. In the 12 week DFP, participants were given one of three doses (SP 320 mg, SP 640mg, and SP 960 mg) using the Time-to-Event Continual Reassessment Method to determine the maximum therapeutic dose (MTD). Once the MTD was determined the RCT phase was begun, participants were allocated to receive either the predetermined MTD (960 mg) in the DFP or a placebo to obtain preliminary evidence of efficacy of SP on LUTS. Safety data consisted of the Common Terminology for Adverse Events criteria for nausea, gastritis, and anorexia. Efficacy of the MTD was evaluated by weekly symptom data and voiding diary. A pill diary was used to ensure the intervention fidelity.
Interventions
DRUGSaw Palmetto
1 of 3 doses of Saw Palmetto (320, 640, 960mg/day)
DRUGsoybean oil soft gel
placebo (soybean oil soft gel)
Sponsors
Michigan State University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
MALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 21 years or older * Adenocarcinoma of the prostate * Serum Prostate Specific Antigent (PSA) ≤ 40ng/ml * Combined Gleason Score ≤ 8 * Karnofsky level of performance of \> 70% * Consented to undergo definitive Radiation Therapy
Exclusion criteria
* Stage T4 or M1 * Patient using own supply of Saw Palmetto or any other supplement containing the following herbs: Pygeum (African Plum), Urtica Dioica (Stinging nettle), Cucurbita peponis (pumpkin seed), PC-SPES (combination of 8 herbs), Beta-sitsterol (plant sterols) or Cernilton (rye grass pollen). * Prior pelvic radiation therapy * Abnormality in liver and kidney function as evidenced by greater than twice the normal values of Blood Urea Nitrogen (BUN), serum creatine, serum transaminases, and alkaline phosphatase. * Uncontrolled hypertension despite use of antihypertensive medication * Presence of major psychiatric or medical illness (e.g., major cardiovascular events within the previous 12 months)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility | Baseline to Week 12 for each phase. | Assess a Saw Palmetto supplementation protocol for feasibility by evaluation if at least 70% of eligible men consent, and if at least 70% of men enrolled at each dose complete the study. |
| Efficacy | HRQOL: Baseline, week 12, 14, & 22. IPSS: Baseline, week 3-12, 14, & 22. | Evaluate preliminary efficacy of Saw Palmetto at the MTD as compared to the placebo group with respect to Health-Related Quality of life (HRQOL) including physical functioning and symptoms. The outcomes were measured using 1) the International Prostate Symptoms Score (IPSS) and 2) the total and subscales of the Functional Assessment of Cancer Therapy-Prostate (FACT-P). The IPSS which ranges from 0-35. A lower score indicates better symptoms. The FACT-P has the following subscores and ranges: emotional well-being (0-24), functional well-being (0-28), physical well-being (0-28), social well-being (0-28), and prostate-specific concerns (0-48). The FACT-P total is comprised of the sum of the subscales and ranges from 0-156. For the FACT-P, a higher score indicates better quality of life. Each values was created as an average over time from a linear mixed effects model that adjusted for baseline values. |
| Number of Participants With Dose Limiting Toxicities to Determine the Maximum Tolerated Dose | Baseline to Week 12 | Dose limiting toxicities was defined as the Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher for gastrointestinal symptoms (nausea, gastritis, anorexia). The maximum tolerated dose (MTD) was established among 320mg, 640mg,or 960mg, at which less than 10% of men report less than a grade 2 of gastrointestinal symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Saw Palmetto Soft Gel 320mg/Day Participants in this arm received 320mg/day of Saw Palmetto Soft Gel capsules. | 3 |
| Phase 1: Saw Palmetto Soft Gel 640mg/Day Participants in this arm received 640mg/day of Saw Palmetto Soft Gel capsules. | 4 |
| Phase 1: Saw Palmetto Soft Gel 960mg/Day Participants in this arm received 960mg/day of Saw Palmetto Soft Gel capsules. | 20 |
| Active Comparator: Phase 2: RCT Phase- Saw Palmetto Patients received the predetermine the maximum therapeutic dose of Saw Palmetto Soft Gel capsules in phase 1, which is 960mg | 10 |
| Placebo Comparator: Phase 2: RCT Phase- Placebo Patients received Soybean Oil Soft Gel as the placebo treatment | 11 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 2 | 1 | 0 |
| Overall Study | Other | 0 | 1 | 1 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Phase 1: Saw Palmetto Soft Gel 320mg/Day | Phase 1: Saw Palmetto Soft Gel 640mg/Day | Phase 1: Saw Palmetto Soft Gel 960mg/Day | Active Comparator: Phase 2: RCT Phase- Saw Palmetto | Placebo Comparator: Phase 2: RCT Phase- Placebo |
|---|---|---|---|---|---|---|
| Age, Continuous | 67.29 years STANDARD_DEVIATION 9.16 | 71 years STANDARD_DEVIATION 3 | 62.75 years STANDARD_DEVIATION 12.09 | 62.1 years STANDARD_DEVIATION 5.3 | 66.70 years STANDARD_DEVIATION 11.3 | 67.82 years STANDARD_DEVIATION 7.22 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 3 Participants | 4 Participants | 14 Participants | 8 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 0 Participants | 0 Participants | 5 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 41 Participants | 3 Participants | 4 Participants | 15 Participants | 9 Participants | 10 Participants |
| Region of Enrollment United States | 48 participants | 3 participants | 4 participants | 20 participants | 10 participants | 11 participants |
| Sex/Gender, Customized Male | 48 participants | 3 participants | 4 participants | 20 participants | 10 participants | 11 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 27 | 0 / 10 | 0 / 11 |
| serious Total, serious adverse events | 0 / 27 | 0 / 10 | 0 / 11 |
Outcome results
Primary
Efficacy
Evaluate preliminary efficacy of Saw Palmetto at the MTD as compared to the placebo group with respect to Health-Related Quality of life (HRQOL) including physical functioning and symptoms. The outcomes were measured using 1) the International Prostate Symptoms Score (IPSS) and 2) the total and subscales of the Functional Assessment of Cancer Therapy-Prostate (FACT-P). The IPSS which ranges from 0-35. A lower score indicates better symptoms. The FACT-P has the following subscores and ranges: emotional well-being (0-24), functional well-being (0-28), physical well-being (0-28), social well-being (0-28), and prostate-specific concerns (0-48). The FACT-P total is comprised of the sum of the subscales and ranges from 0-156. For the FACT-P, a higher score indicates better quality of life. Each values was created as an average over time from a linear mixed effects model that adjusted for baseline values.
Time frame: HRQOL: Baseline, week 12, 14, & 22. IPSS: Baseline, week 3-12, 14, & 22.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 1: Men in 320mg/Day DFP | Efficacy | FACT-P emotional well-being | 20.77 units on a scale | Standard Deviation 0.84 |
| Phase 1: Men in 320mg/Day DFP | Efficacy | FACT-P physical well-being | 24.00 units on a scale | Standard Deviation 0.86 |
| Phase 1: Men in 320mg/Day DFP | Efficacy | FACT-P total | 124.77 units on a scale | Standard Deviation 4.37 |
| Phase 1: Men in 320mg/Day DFP | Efficacy | FACT-P social well-being | 23.38 units on a scale | Standard Deviation 1.08 |
| Phase 1: Men in 320mg/Day DFP | Efficacy | FACT-P functional well-being | 22.24 units on a scale | Standard Deviation 1.3 |
| Phase 1: Men in 320mg/Day DFP | Efficacy | FACT-P Prostate specific concern | 35.13 units on a scale | Standard Deviation 1.92 |
| Phase 1: Men in 320mg/Day DFP | Efficacy | IPSS | 10.54 units on a scale | Standard Deviation 1.29 |
| Phase 1: Men in 640mg/Day DFP | Efficacy | FACT-P Prostate specific concern | 33.81 units on a scale | Standard Deviation 1.82 |
| Phase 1: Men in 640mg/Day DFP | Efficacy | IPSS | 9.41 units on a scale | Standard Deviation 1.21 |
| Phase 1: Men in 640mg/Day DFP | Efficacy | FACT-P total | 124.48 units on a scale | Standard Deviation 4.18 |
| Phase 1: Men in 640mg/Day DFP | Efficacy | FACT-P emotional well-being | 21.62 units on a scale | Standard Deviation 0.79 |
| Phase 1: Men in 640mg/Day DFP | Efficacy | FACT-P functional well-being | 21.20 units on a scale | Standard Deviation 1.25 |
| Phase 1: Men in 640mg/Day DFP | Efficacy | FACT-P physical well-being | 25.67 units on a scale | Standard Deviation 0.81 |
| Phase 1: Men in 640mg/Day DFP | Efficacy | FACT-P social well-being | 21.02 units on a scale | Standard Deviation 1.01 |
Primary
Feasibility
Assess a Saw Palmetto supplementation protocol for feasibility by evaluation if at least 70% of eligible men consent, and if at least 70% of men enrolled at each dose complete the study.
Time frame: Baseline to Week 12 for each phase.
Population: Number of men who started
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: Men in 320mg/Day DFP | Feasibility | 3 Participants |
| Phase 1: Men in 640mg/Day DFP | Feasibility | 3 Participants |
| Phase 1: Men in 960mg/Day DFP | Feasibility | 16 Participants |
| Phase 2: Saw Palmetto 960 mg RCT | Feasibility | 6 Participants |
| Phase 2: Placebo RCT | Feasibility | 9 Participants |
Primary
Number of Participants With Dose Limiting Toxicities to Determine the Maximum Tolerated Dose
Dose limiting toxicities was defined as the Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or higher for gastrointestinal symptoms (nausea, gastritis, anorexia). The maximum tolerated dose (MTD) was established among 320mg, 640mg,or 960mg, at which less than 10% of men report less than a grade 2 of gastrointestinal symptoms.
Time frame: Baseline to Week 12
Population: Number of participants reporting adverse events at grade 2 or higher, according to the TITE-CRM algorithm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1: Men in 320mg/Day DFP | Number of Participants With Dose Limiting Toxicities to Determine the Maximum Tolerated Dose | 0 participants |
| Phase 1: Men in 640mg/Day DFP | Number of Participants With Dose Limiting Toxicities to Determine the Maximum Tolerated Dose | 0 participants |
| Phase 1: Men in 960mg/Day DFP | Number of Participants With Dose Limiting Toxicities to Determine the Maximum Tolerated Dose | 0 participants |
Comparison: The time-to-event continual reassessment method (TITE-CRM) was used The TITE-CRM incorporated a decision rule for the allocation of next participant to a dose of SP based on the current estimate of toxicity. The first men were allocated to lowest dose (320 mg); when no adverse event was reported during 12 weeks, the dose was increased to 640 mg for next men, and then to 960 mg in the absence of advert event.