HN-BIO 02: A Phase II Randomized Study of the Effects of Delayed Elective Radiotherapy on Head and Neck MRI and Immune Response Biomarkers (HN-Bio 02)

This is a single centre prospective exploratory study of effects of radiation therapy on biomarker development in patients with newly diagnosed (head and neck squamous cell carcinoma) HNSCC receiving curative therapy. This research is part 2 of the HN-BIO study.

Study Overview

• Status: Recruiting
• Conditions: Squamous Cell Carcinoma of Head and Neck
• Intervention / Treatment: Radiation: Standard of care external beam radiotherapy (single integrated boost); Radiation: Standard of care external beam radiotherapy (two-phase treatment)

Detailed Description

This study will recruit up to 40 patients planned to receive curative (chemo) radiotherapy for (head and neck squamous cell carcinoma) HNSCC with primary tumor and/or involved lymph node suitable for repeat biopsy in clinic. After being informed about the study and potential risks, patients giving written informed consent will be randomized to receive conventional radiotherapy (single integrated boost or conventional two-phase at clinician discretion) or reversed two-phase treatment with delayed irradiation of elective nodal volumes. Patients will not be informed of their randomization result.

Patients in both arms will undergo a baseline functional magnetic resonance imaging (fMRI) scan and within 72 hours, when possible, a biopsy of the primary tumor +/- lymph node will be performed in an out-patient clinic. If a suitable biopsy has been recently performed as part of diagnostic work up the baseline biopsy on study will be omitted when possible. In week 2 of radiotherapy, patients will have a second fMRI scan and a paired biopsy within 72 hours of the scan, where possible. A further optional biopsy and paired fMRI scan in week 4 will be considered for patients who are tolerating therapy without >G1 toxicities. 16-24 hours prior to each biopsy the patient will take oral pimonidazole. At the time of each biopsy a blood draw will be performed.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrew McPartlin, MD; Phone Number: 416-946-2132; Email: andrew.mcpartlin@rmp.uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre
      • Contact: Andrew McPartlin, MD; Phone Number: (416) 946-4501 x 4855; Email: andrew.mcpartlin@uhn.ca

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age >/= 18 years
• Histologically proven Head and Neck Squamous Cell carcinoma
• Primary or nodal disease > 3cm for biomarker imaging
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Planned for curative surgery or (chemo)radiotherapy
• Willingness to undergo repeat MRI imaging
• Able to receive and understand verbal and written information regarding study and able to -give written informed consent
• Adequate renal function: Calculated creatinine clearance >/= 30ml/min
• Be able to lie comfortably on back for 1 hour

Exclusion Criteria:

• As judged by investigator evidence of systemic disease that makes unsuitable for study
• Contra-indication for serial MRI scans
• Previous solid tumor treated within last 5 years
• Pregnancy
• History of gadolinium contrast allergy
• Non-reversible clotting abnormality

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: Arm 1: Integrated Boost Radiotherapy; External beam radiotherapy 70Gy in 35 fractions to head and neck tumour and 56 Gy in 35 fraction to elective nodal regions. This will be given as single integrated boost or two-phase treatment at clinician discretion.	Radiation: Standard of care external beam radiotherapy (single integrated boost); 70Gy in 35 fractions, 56 Gy in 35 fractions. Oral Pimonidazole 200 mg and 300 mg tablets.
Active Comparator: Arm 2: Two Phase Radiotherapy; Standard of care external beam radiotherapy 70 Gy in 35 fractions to head and neck with delayed 40 Gy in 20 fractions (HPV+ oropharynx) or 50 Gy/25 (all other disease) to elective nodal regions. This will be given as reversed two-phase treatment.	Radiation: Standard of care external beam radiotherapy (two-phase treatment); 70Gy in 35 fractions, delayed 40 Gy in 20 fractions or 50 Gy in 25 fractions. Oral Pimonidazole 200 mg and 300 mg tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirm feasibility of recruitment of HN patients for on treatment repeat biopsy of the primary tumor +/- neck nodes	Achieve a minimum recruitment rate of one patient per month.	7 weeks
Change in fMRI during radiotherapy	Study association of changes in fMRI and tissue biomarkers during radiotherapy. Assessed through hypoxic regions visible on imaging scans.	7 weeks
Assess changes in tumor microenvironment during differing radiotherapy scheduling via repeat biopsy.	Assess effect of varying radiotherapy treatment volumes on changes in tumor microenvironment via repeat biopsy before and during radiotherapy. Quantify effect of delayed treatment of dLN on dynamic changes tumor immune micro-environment and hypoxia status during radiotherapy. Perform exploratory analysis of study data correlating changes in tumor microenvironment and hypoxia status with disease response to therapy.	7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validate novel and established fMRI imaging as predictive and prognostic radiotherapy biomarkers for HNSCC	Correlate changes in TME and hypoxia with changes in fMRI on repeat assessment. Correlate fMRI characterized tumor with pathological post-operative specimen.	7 weeks

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2025
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: June 27, 2024
• First Submitted That Met QC Criteria: June 27, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: 24-5510

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No