Radiation Cystitis Treated With Pentosan Polysulfate Sodium Trial

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of pentosan polysulfate sodium versus placebo and in patients with radiation cystitis who have received radiation therapy in pelvic region.

Detailed Description
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RCT-PPS is a phase II/III study evaluating the efficacy, safety, and tolerability of pentosan polysulfate sodium (PPS) versus placebo to patients with radiation cystitis who have received radiation therapy in pelvic region. Approximately 72 patients were planned to be randomized in RCT-PPS trial in a 1:1 ratio to treatment with either PPS or placebo. Patients will receive oral treatment with 16 weeks (PPS 100mg three times a day for 8 weeks and then with PPS 100mg twice daily for another 8 weeks).

Official Title
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A Randomized, Controlled, Phase II/III Trial to Evaluate the Efficacy and Safety of U101 Oral Capsules in Radiation-induced Cystitis

Conditions
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Radiation Cystitis

Intervention / Treatment
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* Drug: Pentosan Polysulfate Sodium 100 MG Oral Capsule
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in the study protocol. Patients must be ≥20 years of age Patients must have received definitive radiation therapy for cancer in pelvic area. Time from the end of radiation therapy to radiation cystitis must be longer than 6 months. Radiation cystitis with lower urinary tract symptoms or hematuria. Exclusion Criteria: Abnormal liver function with indication of AST, ALT, or total bilirubin ≥ 1.5 times higher than normal Abnormal renal function with serum creatinine ≥ 1.5 times higher than normal Abnormal coagulation profile with PT/INR higher than normal Thrombocytopenia with platelet counts < 100,000/μL Pregnant or breastfeeding, expecting to pregnancy, or positive for pregnancy test Patients who have systemic inflammatory symptoms during screening period (ie, fever up to 38℃ or WBC counts >12,000/μL) Patients with known urinary tract infection within 6 months of randomization. Any previous intravesical instillation within 6 months of randomization (ie, hyaluronic acid instillation) Any previous hyperbaric oxygen therapy within 6 months of randomization Any previous treatment with pentosan polysulfate sodium within 6 months of randomization Has history of thrombocytopenia, hemophilia or bladder cancer Has known history of Human Immunodeficiency Virus (HIV) or organ transplantation Has known history of drug allergy to pentosan polysulfate sodium Has hematuria caused by clinically active urolithiasis or urothelial carcinoma

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pentosan Polysulfate Sodium<br>U101 is available as a capsule containing 100 milligrams (mg) of pentosan polysulfate sodium. Subjects will be administered U101 at a dose of 300 milligrams (mg) three times daily (tid) for the initial 8 weeks and then 200 milligrams (mg) twice daily (bid) for another 8 weeks during the study. | Drug: Pentosan Polysulfate Sodium 100 MG Oral Capsule<br>* Pentosan Polysulfate Sodium 100 mg three times daily (tid) for 0-8 weeks Pentosan Polysulfate Sodium 100 mg twice daily (bid) for 9-16 weeks<br>* Other names: PPS;|
| Placebo Comparator: Placebo Control<br>Placebo to match U101 is available as a capsule in 100 milligrams (mg). Subjects will be administered placebo at a dose of 300 milligrams (mg) three times daily (tid) for the initial 8 weeks and then 200 milligrams (mg) twice daily (bid) for another 8 weeks during the study. | Drug: Placebo<br>* Placebo 100 mg three times daily (tid) for 0-8 weeks Placebo 100 mg twice daily (bid) for 9-16 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete remission in lower urinary tract symptoms and hematuria | Number of participants without lower urinary tract symptoms and hematuria assessed by ESOU 2019 and CTCAE v5.0 | From date of randomization throughout the treatment period up to 5 years | 
| Time to complete remission | Time from randomization to complete remission of lower urinary tract syndromes and hematuria | From date of randomization to study completion up to 5 years | 
| Time to hematuria recurrence | Time from randomization to recurrence of hematuria | From date of randomization to study completion up to 5 years | 
| Assessment of quality of life | Functional Assessment of 36-Item Short Form Survey (SF-36) | From date of randomization to study completion up to 5 years | 
| Assessment of symptoms | Functional Assessment of Expanded Prostate Cancer Index Composite-26 (EPIC-26) | From date of randomization to study completion up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of hospitalization | Overall days of hospitalization due to radiation cystitis | From date of randomization to study completion up to 5 years | 
| Number of invasive procedures | Percentage of patients underwent transurethral cauterization of bladder bleeders or transurethral clots evacuation. | From date of randomization to study completion up to 5 years | 
| Number of adverse events | Percentage of patients with any adverse event (AE), adverse event (AE) leading to study drug discontinuation, serious adverse event (SAE), and adverse event (AE) related to study drug. | From date of randomization to study completion up to 5 years |