HN-BIO: A Study of Head and Neck MRI and Tumor Microenvironment Biomarkers

Study Overview
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Brief Summary
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The purpose of this study is to explore biomarker development in patients with newly diagnosed Head and neck squamous cell carcinoma (HNSCC) receiving curative therapy.

Detailed Description
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After being informed about the study and potential risks, all patients giving written informed consent will be assigned to Cohort A or Cohort B. Cohort A will recruit up to 40 patients planned to receive curative radiotherapy for HNSCC. Patients will undergo a baseline fMRI (Functional Magnetic Resonance Imaging) scan and within 72 hours a biopsy of the primary tumor will be performed in out-patient clinic. In week 2 of radiotherapy a further biopsy of the primary site will be performed with a paired fMRI performed within 72 hours prior to biopsy assess evolving changes in imaging and tumor microenvironment biomarkers during radiotherapy. A further optional biopsy and paired MRI scan in week 4 will be considered for patients who are tolerating therapy without toxicities. 16-24 hours prior to each biopsy the volunteer will take oral pimonidazole. Cohort B will recruit up to 20 patients planned to receive curative surgery for HNSCC. Each patient will undergo a baseline fMRI scan performed within one week prior to surgery. At time of initial consent they will receive a prescription for oral pimonidazole hydrochloride which they will be asked to take the 16-24 hours before planned surgery. Following surgery whole tumor samples will be processed to permit spatial reconstruction of pimonidazole staining hypoxia to correlate with fMRI imaging.

Official Title
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HN-BIO: A Study of Head and Neck MRI and Tumor Microenvironment Biomarkers

Conditions
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Squamous Cell Carcinoma of Head and Neck

Intervention / Treatment
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* Other: fMRI
* Other: Oral Pimonidazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort A<br>Participants who are to receive standard of care radiotherapy will have one biopsy and MRI scan before starting radiotherapy and during week two of radiotherapy. Participants will also have an the option to consent to an additional biopsy and MRI scan during week 4 of radiotherapy. Oral pimonidazole will be taken the night before each biopsy. | Other: fMRI<br>* Functional Magnetic Resonance Imaging<br>Other: Oral Pimonidazole<br>* 200 mg and 300 mg tablets<br>|
| Other: Cohort B<br>Participants who are to receive standard of care curative surgery will have an MRI scan within one week prior to surgery. Tumor tissue from the surgery will also be collected for research. Oral pimonidazole will be taken the night before surgery. | Other: fMRI<br>* Functional Magnetic Resonance Imaging<br>Other: Oral Pimonidazole<br>* 200 mg and 300 mg tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in tumor microenvironment during radiotherapy | Repeat biopsy will be analyzed for haematoxylin and eosin (H&E), pimonidazole (monoclonal IgG1 antibody, Hypoxyprobe MAb1), endogenous proteins associated with hypoxia and/or immune infiltrate, DNA, and RNA. | Prior to radiotherapy, week 2 and week 4 of radiotherapy | 
| Change in fMRI during radiotherapy | Assessed through hypoxic regions visible on imaging scans | Prior to radiotherapy, week 2 and week 4 of radiotherapy |