INSPIRE: INnovative SABR for Prostate Cancer All IREland

Phase 2RecruitingNCT07552168

Cancer Trials Ireland136 enrolled

Overview

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

136

Conditions

Prostate Adenocarcinoma

Interventions

Next generation Stereotactic Ablative Radiotherapy (SABR)RADIATION

Treatment will prioritise the dominant intraprostatic lesion (DIL) while sparing surrounding organs at risk (OARs).

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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).

Locations (4)

St Luke's Centre for Radiation Oncology at Beaumont Hospital

Dublin, Leinster, Ireland

NOT_YET_RECRUITING

Bon Secours - UPMC Hillman

Cork, Ireland

RECRUITING

UPMC Hillman Cancer Centre at Whitfield Hospital

Waterford, Ireland

RECRUITING

Outcomes

Primary Outcomes

Late GU toxicity

Rate of ≥ Grade 2 version 5 (v5) NCI CTCAE late GU toxicity in next-generation prostate SABR at 2 years.

Time frame: 2 years after last fraction

Secondary Outcomes

Acute GU Toxicity

Acute Grade ≥ 2 GU toxicity ≤12 weeks, using v5 NCI CTCAE

Time frame: ≤12 weeks after last fraction

Acute GI Toxicity

Acute Grade ≥ 2 GI toxicity ≤12 weeks, using v5 NCI CTCAE

Time frame: ≤12 weeks after last fraction

Late GU toxicity at 5 years

Late Grade ≥ 2 GU toxicity at 5 years, using v5 NCI CTCAE

Time frame: 5 years after last fraction

Late GI toxicity at 5 years

Late Grade ≥ 2 GI toxicity at 5 years, using v5 NCI CTCAE

Time frame: 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.

Time frame: 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.

Central Contacts

Cancer Trials Ireland

CONTACT

+35316677211 info@cancertrials.ie

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.