Trial of Quercetin, Bromelain, Rye Flower Pollen & Papain on Reducing Severity of Radiation-Induced Prostatitis

Study Overview
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Brief Summary
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This study will assess the difference in prostatitis symptoms in men with localized prostate cancer following brachytherapy taking Q-Urol relative to placebo.

Detailed Description
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This is a Phase 2, double-blinded, placebo-controlled trial assessing the safety of Q-Urol use after brachytherapy placement in patients with localized prostate cancer. Patients will be randomized in a 1:1 ratio to receiveQ-Urol/Placebo twice daily for 6 weeks after brachytherapy placement. Questionnaires will be administered pre- and post-treatment to assess the change in prostatitis symptoms and quality of life measures. The mean values between groups will be compared.

Official Title
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A Phase II Randomized Controlled Trial of a Supplement Containing Quercetin, Bromelain, Rye Flower Pollen, and Papain on Reducing the Severity of Radiation-Induced Prostatitis

Conditions
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Prostate Adenocarcinoma

Intervention / Treatment
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* Drug: Q-Urol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects aged ≥ 18 years. Men with histologically proven localized prostate adenocarcinoma, stage I - III (as defined by AJCC 8th edition), who have selected treatment with brachytherapy with or without external beam radiation, with or without androgen deprivation therapy. Fluent in speaking and reading English. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1. Adequate organ function as defined as: Hepatic: Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN) aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × institutional ULN Renal: Estimated creatinine clearance ≥ 30 mL/min by Cockcroft-Gault formula: Males: ((140-age)×weight[kg])/(serum creatinine [mg/dL]×72) Highly effective contraception for both male and their female partners of childbearing potential throughout the study and for at least 5 days after last study treatment administration if the risk of conception exists. Median life expectancy ≥ 5 years as calculated by the Lee and Shonberg Index (https://eprognosis.ucsf.edu/leeschonberg.php) Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. Exclusion Criteria: Baseline AUA symptom scores > 15. Prior diagnosis of chronic prostatitis type II through IV. Subject has received systemic therapy intended for the treatment of prostatitis (including herbal supplements) ≤ 14 days of starting study treatment. Subject has received a fluoroquinolone antibiotic (e.g. ciprofloxacin, norfloxacin, ofloxacin levofloxacin, etc.) ≤ 3 days of starting study treatment. Subject is actively on anti-inflammatory medications for other medical conditions, unless approved by PI. Subject has undergone transurethral resection of the prostate (TURP). Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen. History of irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, and interstitial cystitis-bladder pain syndrome (IC/BPS). History of symptomatic hypotension, falls, or syncope History of hypoglycemia. Actively abusing alcohol or drugs Subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: Congestive heart failure Diabetes Pulmonary artery hypertension Any clinically significant condition that requires therapy with diuretic medications for any indication other than the management of hypertension. Other clinically significant disorders that would, in the opinion of the treating investigator, preclude safe study participation. Known prior severe hypersensitivity to investigational product or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3). Known allergy to pineapple or pineapple containing products. Subjects taking prohibited medications as described in Section 7.3 A washout period of prohibited medications for a period of at least 5 half-lives or as clinically indicated should occur prior to the start of treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An asymmetric two-sided group sequential design will be used with an interim analysis for efficacy and futility.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1: Q-Urol<br>Patients will be randomized in a 1:1 ratio to receive Q-Urol, two capsules, twice daily for 6 weeks after brachytherapy placement. Questionnaires will be administered pre- and post-treatment to assess the change in prostatitis symptoms and quality of life measures. The mean values between groups will be compared. | Drug: Q-Urol<br>* Q-Urol is an over-the-counter herbal supplement manufactured by Farr Laboratories. It is a combination product composed of quercetin, pollen extract, bromelain, and papain.<br>|
| Placebo Comparator: Arm 2: Placebo<br>Patients will be randomized in a 1:1 ratio to receive Placebo, two capsules, twice daily for 6 weeks after brachytherapy placement. Questionnaires will be administered pre- and post-treatment to assess the change in prostatitis symptoms and quality of life measures. The mean values between groups will be compared. | Drug: Placebo<br>* placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean peak score of the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) | difference in prostatitis symptoms between treatment and placebo group. | 6 weeks post brachytherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sexual Health Inventory for Men (SHIM) assessment | Health Related Quality of Life (HRQOL) will be assessed with pre- and post- treatment SHIM questionnaires SHIM Scores 1-7 Severe Erectile Dysfunction (ED) 8-11 Moderate ED 12-16 Mild to Moderate ED 17-21 Mild ED 22-25 No signs of ED | 5 weeks post brachytherapy | 
| Impact on serum biomarkers of inflammation. Markers to include erythrocyte sedimentation rate, C-reactive protein, and prostate-specific antigen (PSA). | inflammation markers will be collected pre- and post-brachytherapy for comparison between treatment and placebo groups. | 5 weeks post brachytherapy | 
| adverse events will be characterized for frequency, type ,severity | To assess safety of Q-Urol compared to placebo. | 5 weeks | 
| The Expanded Prostate Cancer Index Composite (EPIC) assessment | Health Related Quality of Life (HRQOL) will be assessed with pre- and post- treatment EPIC questionnaires. Items are standardized to a 0-100 scale and are averaged to calculate a summary score or subscale score. | 5 weeks post brachytherapy | 
| The International Prostate Symptom Score (I-PSS) assessment | Health Related Quality of Life (HRQOL) will be assessed with pre- and post- treatment I-PSS questionnaires. American Urological Association Symptom (AUA) Score Mild = 0-7 Moderate = 8-19 Severe = 20-35 | 5 weeks post brachytherapy | 
| The Rectal Function Assessment Score (R-FAS) assessment | Health Related Quality of Life (HRQOL) will be assessed with pre- and post- treatment questionnaires. Responses to the questions are added up for a total between 0-27. Question 10 does not count toward the total score. | 5 weeks post brachytherapy | 
| number of days days medication is taken for treatement of prostate-related pain. | To assess effect on prostatitis-related pain in men with localized prostate cancer following bracytherapy taking Q-Urol relative to placebo. | 28 days post brachytherapy |