INSPIRE: INnovative SABR for Prostate Cancer All IREland

This is a Phase II, single arm, multi-centre, prospective clinical trial evaluating next generation Stereotactic Ablative Radiotherapy (SABR) for low, intermediate, and eligible high-risk prostate cancer. Eligible patients will receive next generation prostate SABR incorporating toxicity reduction strategies

Study Overview

• Status: Recruiting
• Conditions: Prostate Adenocarcinoma
• Intervention / Treatment: Radiation: Next generation Stereotactic Ablative Radiotherapy (SABR)

Detailed Description

This is a Phase II, single arm, multi-centre, prospective clinical trial evaluating next generation Stereotactic Ablative Radiotherapy (SABR) for low, intermediate, and eligible high-risk prostate cancer. Eligible patients will receive next generation prostate SABR incorporating toxicity reduction strategies: urethral/trigone sparing, rectal hydrogel spacer, and neurovascular bundle preservation [as per Desai POTEN-C trial, Desai et al., 2025].

Treatment will prioritise the dominant intraprostatic lesion (DIL) while sparing surrounding organs at risk (OARs). Planned doses are: DIL 40-50 Gy in 5 fractions delivered on alternate days, prostate CTV 35 Gy, PTV 33.25 Gy, and urethral PRV 32.5 Gy. Eligible high-risk and some intermediate-risk patients may receive 6-12 months of androgen deprivation therapy (ADT)/hormonal therapy at the physician's discretion, provided they have not received >14 weeks prior to registration.

Radiotherapy planning will include advanced image-guided verification with fiducial markers, pre-treatment dosimetry to minimise dose to OARs, and adherence to protocol-defined constraints for urethra, rectum, and neurovascular bundles. Peri-rectal spacers will be inserted 7-10 days prior to CT-simulation to reduce rectal dose. Dose prioritisation allows full coverage of the DIL while sparing urethra, bladder trigone, and neurovascular bundles to minimise genitourinary, rectal, and sexual toxicity.

Follow-up assessments will include clinical evaluation, toxicity reporting using v5 NCI CTCAE, and patient-reported outcome measures (PRO/QoL) at 2-, 4-, 8-, and 12-weeks post-treatment, 6 and 9 months, and annually up to 5 years. Data on biochemical/clinical failure, progression-free survival, and initiation or re-initiation of ADT will also be collected.

A total of 136 patients will be enrolled to achieve 122 evaluable participants, allowing detection of a statistically significant reduction in Grade ≥2 late genitourinary toxicity compared to historical SABR controls.

• Study Type: Interventional
• Enrollment (Estimated): 136
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cancer Trials Ireland; Phone Number: +35316677211; Email: info@cancertrials.ie

Study Locations

• Ireland
  • Cork, Ireland, T12 DV56
    • Recruiting
    • Bon Secours - UPMC Hillman
    • Contact: Bon Secours - UPMC Hillman; Phone Number: +353214861100
    • Principal Investigator: Paul Kelly, Dr
  • Leinster
    • Dublin, Leinster, Ireland, D09 FT51
      • Not yet recruiting
      • St Luke's Centre for Radiation Oncology at Beaumont Hospital
      • Contact: SLRON at Beaumont Hospital; Phone Number: +35317045500
      • Principal Investigator: Brian O'Neill, Professor
• United Kingdom
  • Ulster
    • Belfast, Ulster, United Kingdom, BT9 7AB
      • Not yet recruiting
      • Northern Ireland Cancer Centre (NICC)
      • Contact: NICTN at Belfast Trust; Phone Number: +442896152652
      • Principal Investigator: Suneil Jain, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent obtained prior to any study-related procedures
2. Males ≥ 18 years of age
3. ECOG performance status (PS) 0-2
4. Biopsy-proven prostate adenocarcinoma without neuro-endocrine differentiation (within 18 months prior to registration, unless on active surveillance and re-biopsy not clinically indicated)
5. Gleason score ≤ 4+3
6. Clinical and/or MRI stage T1c-T3a, N0-X, M0-X
7. PSA ≤ 30 ng/ml (within 60 days prior to registration / prior to starting androgen-deprivation therapy (ADT/hormone therapy) [PSA ≤ 15 ng/ml for patients on 5-alpha reductase inhibitors]

8. Patients belonging to one of the following risk groups:

   • Low risk - patients meeting all of the following criteria:

     • Gleason ≤ 6
     • Clinical stage T1c-T2a
     • PSA < 10 ng/ml (within 60 days prior to registration)

   • Intermediate risk - patients meeting any of the following criteria, assuming no high-risk features apply:

     • Gleason 7 (3+4 or 4+3)
     • MRI stage T2b-T2c (N0, M0-X)
     • PSA 10-20 ng/ml (within 60 days prior to registration)

   • High risk - patients with tumours that meet a maximum of one of the following criteria:

     • MRI stage T3a (N0, M0)
     • PSA >20 - ≤30 ng/ml (within 60 days prior to registration)

Exclusion Criteria:

1. Previous malignancy within the last 2 years (except basal cell carcinoma (BCC) or squamous carcinoma of the skin), or if previous malignancy is expected to significantly compromise 5 year survival
2. Prior pelvic radiotherapy
3. Any prior active treatment for prostate cancer (with the exception of ADT). Patients previously on active surveillance are eligible if they continue to meet all other eligibility criteria.
4. Life expectancy <5 years.
5. Bilateral hip prostheses or any other implants/hardware that would introduce substantial CT artefacts
6. Medical conditions likely to make radiotherapy inadvisable e.g. inflammatory bowel disease, significant urinary symptoms.
7. Anticoagulation with warfarin/bleeding tendency making fiducial placement or surgery unsafe in the opinion of the clinician. Note: Anti-platelet agents e.g. aspirin, clopidogrel and DOACs such as apixaban, rivaroxaban are not contraindications to trial entry.
8. Participation in another concurrent treatment protocol for prostate cancer (not including QoL, survivorship, exercise or registry studies).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Next generation Stereotactic Ablative Radiotherapy (SABR); Eligible patients will receive next generation prostate SABR incorporating toxicity reduction strategies: urethral/trigone sparing, rectal hydrogel spacer, and neurovascular bundle preservation.	Radiation: Next generation Stereotactic Ablative Radiotherapy (SABR); Treatment will prioritise the dominant intraprostatic lesion (DIL) while sparing surrounding organs at risk (OARs).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late GU toxicity	Rate of ≥ Grade 2 version 5 (v5) NCI CTCAE late GU toxicity in next-generation prostate SABR at 2 years.	2 years after last fraction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute GU Toxicity	Acute Grade ≥ 2 GU toxicity ≤12 weeks, using v5 NCI CTCAE	≤12 weeks after last fraction
Acute GI Toxicity	Acute Grade ≥ 2 GI toxicity ≤12 weeks, using v5 NCI CTCAE	≤12 weeks after last fraction
Late GU toxicity at 5 years	Late Grade ≥ 2 GU toxicity at 5 years, using v5 NCI CTCAE	5 years after last fraction
Late GI toxicity at 5 years	Late Grade ≥ 2 GI toxicity at 5 years, using v5 NCI CTCAE	5 years after last fraction
Patient-Reported Outcomes (PRO) / Quality of Life (QoL) assessments for all patients via Expanded Prostate Cancer Index Composite Short Form (EPIC-26).	EPIC-26 will be reported at 4 weeks, 12 weeks, 6, 9, and 12 months following treatment and yearly thereafter (until year 5). Response options for each EPIC item form a Likert scale, and multi- scores are transformed linearly to a 0-100 scale with higher scores representing better HRQOL.	4 weeks, 12 weeks, 6, 9, and 12 months, 24 months, 36 months, 48 months, 60 months after treatment
Patient-Reported Outcomes (PRO) / Quality of Life (QoL) assessments for all patients via International Index of Erectile Function (IIEF-5).	IIEF-5 will be reported at 12 weeks, 6 and 12 months following treatment and yearly thereafter (until year 5). IIEF-5 is reported on a scale of 5 to 25 with higher scores representing better function.	12 weeks, 6 and 12 months, 24 months, 36 months, 48 months, 60 months after treatment
Patient-Reported Outcomes (PRO) / Quality of Life (QoL) assessments for all patients via International Prostate Symptom Score (IPSS).	IPSS will be reported at 4 weeks, 12 weeks, 6, 9, and 12 months following treatment and yearly thereafter (until year 5). The total symptom score of IPSS ranges from 0 to 35 where 0 indicates no symptoms and 35 indicates the patient is severely symptomatic.	4 weeks, 12 weeks, 6, 9, and 12 months, 24 months, 36 months, 48 months, 60 months after treatment
Freedom from biochemical or clinical failure.	Freedom from biochemical (Phoenix definition) or clinical (commencement or re-commencement of androgen deprivation therapy >12 weeks after completing the neoadjuvant/adjuvant course of ADT, local recurrence, nodal recurrence and distant metastases) failure.	The primary timepoint of interest is 5 years from registration.
Disease specific survival and overall survival	Disease specific survival and overall survival	5 years from registration.
Progression-free survival (PFS)	Progression-free survival (PFS) - radiographic, clinical or biochemical evidence of local or distant failure.	5 years from registration
To assess commencement or re-commencement of androgen deprivation therapy (ADT)	Eligible high-risk patients and some intermediate risk patients may be planned to receive (or may have already commenced) 6-12 months ADT/hormonal therapy at physician's discretion.	Up to five years post last fraction.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-Reported Outcomes (PRO) / Quality of Life (QoL) assessments for all patients via Penile Shortening and well being questionnaire (PSW E9).	PSW E9 will be reported at baseline, 6 months and 2 years post treatment. PSW E9 is a 9 item questionnaire using a Likert scale 0-4 where higher scores indicate lower satisfaction.	Baseline, 6 months and 2 years post treatment.

Collaborators and Investigators

• Sponsor: Cancer Trials Ireland

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): November 1, 2034

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 20, 2026
• First Posted (Actual): April 27, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Prostate cancer; Prostate adenocarcinoma; SABR; Low-risk prostate cancer; Intermediate-risk prostate cancer; High-risk prostate cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: CTRIAL-IE 24-72

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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