Prostate Reirradiation Toxicity Outcomes Feasibility Study

Study Overview
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Brief Summary
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The RO-PIP trial aims to determine the feasibility of recruitment to a trial randomising patients to salvage ultra-hypofractionated external beam radiotherapy or high dose rate brachytherapy and provide prospective data on patient recorded toxicity outcomes that will inform a future phase III trial.

Detailed Description
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Radiotherapy is the most common curative treatment for non-metastatic prostate cancer, however up to 13% of patients will develop local recurrence within 10 years. Patients can undergo further and potentially curative treatment including salvage surgery, brachytherapy (BT), external beam radiotherapy (EBRT), high intensity focused ultrasound and cryotherapy. Systematic review shows that high dose rate (HDR) BT and stereotactic body radiotherapy (SBRT) have the best outcomes in terms of biochemical control and lowest side effects. The RO-PIP trial aims to determine the feasibility of recruitment to a trial randomising patients to salvage HDR-BT or SBRT and provide prospective data on patient recorded toxicity outcomes that will inform a future phase III trial. The primary endpoint of the RO-PIP feasibility study is to evaluate the patient recruitment potential over 2 years to a trial randomising to either SBRT or HDR-BT for patients who develop local recurrence of prostate cancer following previous radiation therapy. The aim is to recruit 60 patients across 3 sites over 2 years and randomise 1:1 to SBRT or HDR-BT. Secondary objectives include recording clinician and patient reported outcome measures (PROMs) to evaluate treatment-related toxicity. In addition, the study aims to identify potential imaging, genomic and proteomic biomarkers that are predictive of toxicity and outcome based on hypoxia status, a prognostic marker of prostate cancer.

Official Title
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Reirradiation Options for Previously Irradiated Prostate Cancer (RO-PIP): Feasibility Randomised Clinical Trial Investigating Toxicity Outcomes Following Reirradiation With Ultra-hypofractionated External Beam Radiotherapy vs. High Dose Rate Brachytherapy

Conditions
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Prostate Cancer, Radiotherapy Side Effect

Intervention / Treatment
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* Radiation: Brachytherapy
* Radiation: Sterotactic Body Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male individuals aged over 18 years Histologically confirmed locally recurrent prostate cancer (following previous radiotherapy no less than 2 years ago) No metastatic disease Able and willing to provide an informed consent to participate World Health Organisation (WHO) performance status 0-2 Reasonable urinary function (IPSS < 20 and Qmax > 10 ml/second on flow tests) Greater than 10 year life expectancy Exclusion Criteria: Patients who are unfit for a general anaesthetic due to other comorbidities Clinical or radiological evidence of metastatic prostate disease Any patient with a medical or psychiatric condition that impairs their ability to give informed consent Contraindication or intolerance of magnetic resonance scanning Prior prostatectomy History of inflammatory bowel disease.

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: Randomised Feasibility Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High dose-rate brachytherapy<br>Two HDR-BT treatment schedules, either a single fraction 19Gy treatment or 27Gy in 2 fractions approximately 2 weeks apart will be used to be decided by treating centre. | Radiation: Brachytherapy<br>* High Dose-Rate Brachytherapy<br>|
| Experimental: Ultra-hypofractionated external beam radiotherapy<br>Patients will receive 5 fractions of 7.25Gy per fraction which will be delivered alternate days over no more than 2 weeks to provide a total dose of 36.25Gy. | Radiation: Sterotactic Body Radiotherapy<br>* Hypofractionated External Beam Radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Feasibility | Recruitment rates for the whole 24-month recruitment period will be reported overall and per recruiting site. The average recruitment rate per month and in total over the formal monitoring period will be reported. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Reported Toxicity | Incidence of patient reported acute (0-3 months) and long-term toxicity (>3 months) and impact on QoL determined by EPIC-26 (prostate cancer related QoL and functional outcomes), EORTC QLQ-C30 (general QoL score) and international prostate symptom score (IPSS) (urinary and sexual functional outcomes) measurements (Key secondary endpoint). | 0-3 months and >3 months | 
| Clinician Reported Toxicity | Incidence of clinician-reported treatment toxicity as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. | 0-3 months and >3 months |