Squamous Cell Carcinoma of Head and Neck
Conditions
Brief summary
This is a single centre prospective exploratory study of effects of delayed radiation therapy on adaptive immune response in patients with newly diagnosed (head and neck squamous cell carcinoma) HNSCC receiving curative radiotherapy. This research is part 2 of the HN-BIO study.
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 and six weeks post completion of radiotherapy a blood draw will be performed to assess lymphocyte preservation and evidence of differential immune activation.
Interventions
RADIATIONStandard 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.
RADIATIONStandard 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.
Sponsors
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirm feasibility of recruitment of HN patients for on treatment repeat biopsy of the primary tumor +/- neck nodes | 7 weeks | Achieve a minimum recruitment rate of one patient per month. |
| Change in fMRI during radiotherapy | 7 weeks | Study association of changes in fMRI and tissue biomarkers during radiotherapy. Assessed through hypoxic regions visible on imaging scans. |
| Assess changes in tumor microenvironment during differing radiotherapy scheduling via repeat biopsy. | 7 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Validate novel and established fMRI imaging as predictive and prognostic radiotherapy biomarkers for HNSCC | 7 weeks | Correlate changes in TME and hypoxia with changes in fMRI on repeat assessment. Correlate fMRI characterized tumor with pathological post-operative specimen. |
Countries
Canada
Contacts
CONTACTAndrew McPartlin, MD
Outcome results
None listed