Using Fluorine-18-Labeled Fluoro-Misonidazole Positron Emission Tomography To Detect Hypoxia in Head and Neck Cancer Patients

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate low oxygen areas called hypoxia within tumors. These low oxygen areas are thought to be the reason why tumors are more resistant to chemotherapy and radiation treatment. An imaging technique using a hypoxia tracer called fluoromisonidazole (FMISO) can detect low oxygen areas within a tumor. This imaging technique, called a PET scan, uses positively charged particles to detect slight changes in the body's biochemistry and metabolism. FMISO PET scans have been performed in patients with head and neck cancer and have shown the ability to detect low oxygen areas within tumors.

Official Title
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A Study Using Fluorine-18-Labeled Fluoro-Misonidazole Positron Emission Tomography To Detect Hypoxia in Head and Neck Cancer Patients

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Radiation: fluorine-18-labeled fluoro-misonidazole (18F-FMISO)
* Device: 18F-FMISO PET scan
* Device: MRI
* Device: FDG PET/CT scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Cohort 1 and Cohort 2 : Histologically confirmed diagnosis of head and neck carcinoma (excluding nasopharynx, paranasal sinus, salivary, and thyroid malignancies)Any unknown primary squamous cell carcinoma of head and neck with gross nodes is allowed (2002 AJCC) 18 years of age or older Must not have received prior radiation therapy or chemotherapy for this diagnosis. Patients who have had their primary site tumor removed by surgery but still present with grossly enlarged lymph nodes are eligible for this study. Karnofsky performance status ≥ 70. Exclusion Criteria for Cohort 1 and Cohort 2: all nasopharyngeal, paranasal sinus, salivary cancer, and thyroid malignancies prior chemotherapy or radiotherapy within the last three years patients that underwent previous surgical resection for the same disease (except for biopsy or surgery removing primary site tumor but still present with grossly enlarged lymph nodes) any prior radiotherapy to the head and neck region pregnant (confirmed by serum b-HCG in women of reproductive age) or breast feeding Subject Exclusion Criteria for Optional Contrast MRIs • Subjects with a known contraindication to the standard MRI contrast agent (Gadavist, a gadolinium-based contrast agent) and/or a recent estimated glomerular filtration rate (eGFR) of 30 or less will be excluded from all DCE-MRIs, and will instead receive non-contrast MRIs at the DCE-MRI time points.

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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (closed to accrual)<br>Cohort 1 (closed to accrual) Cohort 1 (closed to accrual) There will be no change or intervention in a patient's treatment regime using chemoradiation where both the primary and the neck nodes receive 70Gy. This is currently one accepted standard of care. In a subcohort of patients in Cohort 1 with tumors that are positive for HPV who exhibited no evidence of hypoxia on their baseline 18F-FMISO PET/ CT scan or whose tumors have early resolution of hypoxia on their repeat early response 18F-FMISO PET/CT scan will undergo an alternative treatment where the primary tumor site receives 70Gy while the neck nodes receive 60Gy followed by a planned FDG PET/CT scan and observation. | Radiation: fluorine-18-labeled fluoro-misonidazole (18F-FMISO)<br> <br> Device: 18F-FMISO PET scan<br> <br> Device: MRI<br> <br> Device: FDG PET/CT scan<br> <br> |
| Experimental: Cohort 2 (closed to accrual)<br>Experimental: Cohort 2 (closed to accrual) Cohort 2 HPV+ tumors that demonstrate no evidence of hypoxia on an 18F-FMISO PET scan will receive 30Gy to the surgical bed and neck lymph nodes concurrent with standard chemotherapy followed by a 3-4 month post-treatment neck dissection. In patients who exhibit a complete response with this method of treatment, no further treatment is necessary. For patients within this select group who still have pathologic nodal disease, further standard chemoradiation will be given. All other patients in this cohort (i.e. those who are not in the select HPV+ tumor group outlined above) will receive standard of care treatment following their surgery. | Radiation: fluorine-18-labeled fluoro-misonidazole (18F-FMISO)<br> <br> Device: 18F-FMISO PET scan<br> <br> Device: MRI<br> <br> Device: FDG PET/CT scan<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Report Positive Versus Negative Hypoxia Among Head and Neck Cancers Using 18F-FMISO Dynamic PET | For Cohort 1 | 4 months | 
| To Determine the Pathologic Complete Response of Low Risk HPV+ Oropharyngeal Cancer Patients Without Hypoxia on 18F-FMISO PET Who Received 30Gy | For Cohort 2 - Feasibility will be determined by the pathologic response rate at time of neck dissection | 4 months | 
| Improve the Accuracy of Hypoxia Imaging for Head and Neck Cancers Through Pixel by Pixel Kinetic Analysis of 18F-FMISO Tracer of Dynamic PET Images | Cohort 2 | At baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Detect on Repeat 18F-FMISO PET/CT Scans Whether There is a Reduction of the FMISO-avid or GTVh 5 to 10 Days Into Treatment With Standard Chemoradiotherapy for a Series of Locally Advanced Head and Neck Cancers. | For Cohort 1 | 2 weeks from time of scan | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head, Neck, 04-070