PET With [18F]HX4 in Head and Neck Cancer

Study Overview
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Brief Summary
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The aim of this study is to (i) Determine if tumor hypoxia can be accurately visualised with [18F] HX4 PET imaging in head and neck tumors (ii) correlate the [18F] HX4 PET images with blood and tissue markers and (iii) investigate the quality and optimal timing of [18F] HX4 PET imaging (iv) compare [18F] HX4 PET uptake with [18F] FDG PET uptake before and after treatment.

Detailed Description
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Tumor hypoxia is the situation where tumor cells are or have been deprived of oxygen. Hypoxic tumor cells are usually more resistant to radiotherapy and chemotherapy and more likely to develop metastasis. In head and neck cancer, tumor hypoxia is known to be an important prognostic factor for long term survival. [18F]HX4 is being developed as a diagnostic radiopharmaceutical for PET imaging to find a marker for hypoxia that can be used in standard clinical practice. Current hypoxia tracers lack reliable image quality and kinetics. Because of the short half life and clearance, we expect that [18F]HX4 will have a higher tumor to background ratio than current nitro-imidazole hypoxia markers such as [18F]-misonidazole. The clinical use of a reliable, non-invasive and easy to use hypoxia imaging agent could allow selection of patients most likely to benefit from hypoxia modifying therapies. Included are eligible patients with head and neck squamous cell carcinoma (T2, T3, T4, any N, M0) with tumor diameter ≥ 2,5 cm of the oral cavity, oropharynx, hypopharynx or larynx, planned to be treated with curative primary radiation treatment (+/- concurrent chemotherapy). Before treatment a standard planning [18F]FDG PET-CT will be performed, a blood sample is drawn and baseline [18F]HX4 PET scans will be performed. 18F-HX4 scans will be repeated after radiotherapy treatment with 20 +/- 4 Gy (approximately two weeks). Three months after the end of treatment a [18F]FDG PET scan will be performed.

Official Title
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Non Invasive Imaging of [18F]HX4 With Positron-Emission-Tomography (PET) in Head and Neck Cancer.

Conditions
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Cancer of the Head and Neck

Intervention / Treatment
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* Procedure: Injection of [18F]HX4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological confirmed HNSSC of the oral cavity, oropharynx, hypopharynx, larynx, T2-T3-T4, any N, M0 Tumor diameter ≥ 2,5 cm WHO performance status 0 to 2 Scheduled for primary curative (concurrent chemo-) radiotherapy No previous surgery to the head and neck No previous radiation to the head and neck Adequate renal function (calculated creatinine clearance at least 60 ml/min). The patient is willing and capable to comply with study procedures 18 years or older Have given written informed consent before patient registration Exclusion Criteria: No recent (< 3 months) myocardial infarction No Uncontrolled infectious disease Not pregnant or breast feeding and willing to take adequate contraceptive measures during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [18F]HX4 PET<br>Injection of [18F]HX4 | Procedure: Injection of [18F]HX4<br>* Injection of [18F]HX4 before treatment (baseline) and after radiotherapy with 20 +/-4 Gy: [18F]HX4 PET scans; 444 MBq (12 mCi) [18F]HX4 administrated via a bolus IV injection. Image acquisition: static scan at 240 min p.i. Venous blood sampling: before injection of [18F]HX4 (blood hypoxia markers) Follow-up (3 months after treatment): [18F]FDG PET in treatment position<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visualisation of tumor hypoxia with [18F] HX4 PET imaging | Visualisation of tumor hypoxia with [18F] HX4 PET imaging | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observe spatial and temporal stability of [18F] HX4 PET images |  | 2 years | 
| Correlation of [18F] HX4 with local tumor recurrence and survivalG PET |  | 2 years | 
| Image quality of [18F] HX4-PET at different time points |  | 2 years | 
| Kinetic analysis of HX4 |  | 2 years | 
| Correlation of hypoxia imaging with blood hypoxia markers |  | 2 years | 
| Correlation of hypoxia imaging with tumor tissue biomarkers |  | 2 years | 
| Spatial correlation of [18F] HX4-PET with [18F] FDG PET pre-treatment |  | 2 years | 
| Spatial correlation of [18F] HX4-PET with [18F] FDG PET three months after treatment |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer of the Head and Neck, [18F]HX4, hypoxia, PET, phase II trial