Cancer, Cervical Cancer, Endometrial Cancer, Prostate Cancer, Rectal Cancers
Conditions
Brief summary
This phase II, registry-based cohort-multiple randomized controlled trial (cmRCT) evaluates whether daily online adaptive radiotherapy (ART) enables the safe delivery of hypofractionated, iso-biologically equivalent (EQD2) external beam radiotherapy compared with standard-of-care (SOC) fractionation. Conventional radiotherapy requires generous planning target volume (PTV) margins to account for inter-fraction anatomical variation, which increases radiation exposure to surrounding organs at risk (OARs) and may contribute to toxicity. Modern ART platforms using daily on-table imaging (kV-CBCT or MRI guidance) allow real-time contour adaptation and online plan re-optimization based on same-day anatomy. This approach enables margin reduction while maintaining target coverage and may permit safe hypofractionation. Eligible patients enrolled in an institutional prospective registry will be randomized (1:1) to receive either SOC radiotherapy or hypofractionated ART across multiple pelvic disease strata (post-prostatectomy prostate cancer, intact prostate cancer, endometrial cancer, cervical cancer, and rectal cancer). The primary objective is to demonstrate non-inferiority of hypofractionated ART compared with SOC in terms of cumulative incidence of Grade ≥2 toxicity (CTCAE v5). Secondary outcomes include acute and late toxicity, oncologic outcomes (progression-free survival, locoregional failure, distant metastases, overall survival), patient-reported outcomes, treatment efficiency, and dosimetric parameters. A Bayesian monitoring framework with pre-specified safety and futility stopping rules will be used to ensure patient safety and clinical equipoise throughout the trial.
Interventions
RADIATIONAdaptive Hypofractionated Radiotherapy
Adaptive Radiotherapy (ART) in this study is a real-time, online daily adaptation approach in which high-resolution on-table imaging (kV-CBCT or real-time MRI) is performed prior to each fraction, with the treatment plan immediately recalculated or re-optimized using reduced PTV margins before delivery if needed, enabling safe hypofractionation through tighter margins.
RADIATIONStandard-of-care Radiotherapy
Planned radiotherapy delivered according to physician discretion, without daily online contour adaptation or plan re-optimization prior to treatment delivery.
Sponsors
Centre hospitalier de l'Université de Montréal (CHUM)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
\- Enrolled in PERa registry (CHUM CER 17.0.32), consented to contact for investigational trials, consented to serve as control, and randomly selected to be offered the experimental intervention.
Exclusion criteria
\- For intact prostate stratum : 1. Contraindications to MRI (e.g., pacemaker, potentially mobile metal implant, claustrophobia). 2. Hip replacement, or other pelvic metalwork which causes significant artefact on MRI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Physician-reported Grade 2+ toxicity | 24 months | The primary endpoint is the cumulative incidence of physician-reported Grade 2+ toxicity (CTCAE v5) occurring within 24 months from the completion of radiotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute adverse effects | 3 months | — |
| EORTC QLQ-C30 Global Health Status / Quality of Life Score | 12 and 24 months | For all patients |
| EPIC-26 Domain Scores | 12 and 24 months | Specifically for prostate cancer strata |
| Progression free survival | 24 months | — |
| Time to distant metastases | 24 months | — |
| Treatment efficiency | Up to four weeks | Measured as the total time on the treatment table per fraction and the cumulative treatment time across all fractions. |
| Dosimetric Assessment | Up to four weeks | — |
Countries
Canada
Contacts
CONTACTMom Phat
CONTACTEva Eva Nkurunziza
PRINCIPAL_INVESTIGATORMaroie Barkati, MD
Centre hospitalier de l'Université de Montréal (CHUM)
Outcome results
None listed