Prostate Reirradiation Toxicity Outcomes Feasibility Study (RO-PIP)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Prostate Cancer; Radiotherapy Side Effect
• Intervention / Treatment: Radiation: Brachytherapy; Radiation: Sterotactic Body Radiotherapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ann Henry; Phone Number: 0113 2067630; Email: a.henry@leeds.ac.uk
• Study Contact Backup: Name: Jim Zhong; Phone Number: 0113 2067630; Email: j.zhong@leeds.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High dose-rate brachytherapy; 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; High Dose-Rate Brachytherapy
Experimental: Ultra-hypofractionated external beam radiotherapy; 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; Hypofractionated External Beam Radiotherapy

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Imaging biomarkers	MRI biomarkers at 1 month and 1 year post-treatment predictive of toxicity based on PROMs.	1 month and 12 months
Imaging Reproducibility	Multiple measures of image quality and reproducibility of prostate functional imaging (e.g. diffusion coefficient values from IVIM sequences) for measuring tumour biology will be summarised.	Baseline, 1 and 12 months
Hypoxia Gene Signature	Hypoxia levels based on a hypoxia associated gene signature obtained from the pre-salvage RT biopsy correlated with MRI biomarkers.	Baseline
Proteomic Biomarkers	Changes in the levels of inflammatory cytokine signatures from urine and blood obtained at baseline and after reirradiation in relation to PROMs.	Baseline, 1, 3 and 6 months

Collaborators and Investigators

• Sponsor: University of Leeds
• Investigators: Principal Investigator: Ann Henry, University of Leeds

Study record dates

Study Major Dates

• Study Start (Anticipated): November 15, 2022
• Primary Completion (Anticipated): November 15, 2024
• Study Completion (Anticipated): November 15, 2026

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: November 5, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 14, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 21/YH/0305

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No