A Phase 2 interventional study of Pulsed Adaptive Radiotherapy Combined with Pembrolizumab with or without chemotherapy in Head and Neck Squamous Cell Carcinoma (HNSCC), sponsored by University Health Network, Toronto. Not yet recruiting at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-22.
Sponsored by University Health Network, Toronto · Phase 2, Interventional, and Treatment
The ORION study will evaluate a novel treatment approach for patients with recurrent, metastatic, oligometastatic, or locoregionally incurable head and neck squamous cell carcinoma (HNSCC). Participants will receive pulsed adaptive radiotherapy delivered in 3 to 5 treatment courses approximately 10 days apart, alongside standard-of-care pembrolizumab with or without chemotherapy. Using advanced imaging and adaptive treatment planning, radiotherapy will be tailored to changes in tumor size and surrounding tissues throughout treatment. The study will assess safety, disease control, progression-free survival, quality of life, and biological markers of treatment response. Researchers hypothesize that combining pulsed radiotherapy with systemic therapy will improve 12-month progression-free survival from 17% to 32%, potentially leading to improved outcomes for patients with advanced head and neck cancer.
1,711 studies on the registry are indexed under Squamous Cell Carcinoma of Head and Neck; 544 are open to participants now.
This study's planned enrollment of 48 is close to the median of 50 across 1,456 interventional studies indexed under Squamous Cell Carcinoma of Head and Neck.
Browse Squamous Cell Carcinoma of Head and Neck studies →University Health Network, Toronto is the lead sponsor of 1,432 studies on the registry; 292 are open to participants now.
Of its 17 completed or terminated interventional studies of FDA-regulated products, 3 (18%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Combination Product: Pulsed Adaptive Radiotherapy Combined with Pembrolizumab with or without chemotherapy
The primary tumor in the head and neck region, or dominant metastatic site, will be treated with pulsed RT consisting of 8 Gy pulses delivered every 10-11 days for a total of 5 pulses, delivered exclusively with online adaptive radiotherapy on the Varian Ethos platform. Concomitantly, patients will be treated with the standard systemic treatment with pembrolizumab with or without chemotherapy.
12-Month Progression-Free Survival
12-month progression-free survival will be estimated using the Kaplan-Meier method. The proportion of patients progression-free at 12 months will be compared to the historical benchmark of 17%. The study will be considered positive if the lower bound of the 95% confidence interval exceeds 17%.
Time frame: 12 months
12-Month Modified Progression-Free Survival (mPFS)
Modified progression-free survival is defined as the time from study enrollment to disease progression that is no longer amenable to local salvage radiotherapy or death from any cause, whichever occurs first.
Time frame: 12 months
Treatment-Related Adverse Events
The incidence, severity, and type of acute and late treatment-related adverse events will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 6.0.
Time frame: 12 Months
Changes in Patient-Reported Quality of Life
Assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) with higher scores indicating better quality of life. Changes from baseline will be assessed at each study time point.
Time frame: 12 Months
Changes in Patient-Reported Quality of Life and Functional Outcomes
Assessed using the EORTC Head and Neck Cancer Module (QLQ-H\&N43). Scores range from 0 to 100 scale where for the functional scales, higher scores indicate better functioning. For symptom scales and symptom items, higher scores indicate greater symptom burden or worse symptoms. Changes from baseline over the study period will be evaluated.
Time frame: 12 Months
Swallowing Function
Swallowing function will be assessed using the Functional Oral Intake Scale (FOIS), where scores range from 1 to 7, where 1 indicates no oral intake (nothing by mouth) and 7 indicates a full oral diet with no restrictions. Higher scores indicate better oral intake and swallowing function. Changes from baseline over the study period will be evaluated.
Time frame: 12 Months
Changes in Patient-Reported Quality of Life and Functional Outcomes
Assessed using the Performance Status Scale for Head and Neck Cancer (PSS-HN), which evaluates three domains: Normalcy of Diet, Eating in Public, and Understandability of Speech. Each domain is scored separately on a scale from 0 to 100, with higher scores indicating better function and less impairment. Changes from baseline over the study period will be evaluated.
Time frame: 12 Months
Median Progression-Free Survival (PFS)
Estimated using the Kaplan-Meier method with 95% confidence intervals
Time frame: 12 months
Median Overall Survival (OS)
Estimated using the Kaplan-Meier method with 95% confidence intervals
Time frame: 12 months
Objective Response Rate (ORR)
Reported as a proportion with 95% confidence intervals
Time frame: 12 months
Duration of Response (DoR)
Estimated using the Kaplan-Meier method with 95% confidence intervals
Time frame: 12 months
Time to Next Systemic Therapy
Estimated using the Kaplan-Meier method, with patients censored at last contact if they have not initiated next-line therapy
Time frame: 12 months
Health Economic Impact
Health economic outcomes will be assessed through measures of healthcare resource utilization (Total treatment visits, imaging utilization, resource utilization) compared to historical conventional palliative RT cohorts.
Time frame: 12 months
Financial Toxicity
Patient-reported financial toxicity using Financial Toxicity Questionnaire, with higher scores indicating less financial distress (better financial well-being) and lower scores indicating greater financial toxicity (worse financial burden).
Time frame: 12 months
Start is estimated for Nov 2026; primary completion for Sep 2029, 34 months later.
Of 279 non-industry phase 2 interventional studies under Squamous Cell Carcinoma of Head and Neck, half reached primary completion within 56 months of starting (the median), counting those still running; a quarter within 36 and three quarters within 82. This study's planned 34 months is below that.
Counting every sponsor, half of 348 studies reached it within 50 months; a quarter within 34 and three quarters within 79.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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