PET CT With HX4 in Cervix Cancer

Study Overview
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Brief Summary
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The aim of this study is: to determine if tumor hypoxia can be accurately visualised with [18F]HX4 PET imaging in cervix cancer, to correlate the [18F]HX4 PET images with blood and tissue markers, to investigate the quality and optimal timing of [18F]HX4 PET images, to compare [18F]HX4 PET uptake with [18F]FDG PET uptake before and after treatment and analyze correlation with responses

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 Cervix 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, the investigators expect that [18F]HX4 will have a higher tumor to background ratio than current nitro-imidazole hypoxia markers such as [18F]-misonidazole. In a recent phase 1 clinical study from van Loon et al, PET-imaging with [18F]HX4 was feasible without any toxicity. 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.

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

Conditions
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Cervix Cancer

Intervention / Treatment
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* Other: injection with [18F] HX4 and PET imaging


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Histologically confirmed cervix carcinoma (squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma) tumor stages FIGO IB - IVA WHO performance status 0 to 2 Scheduled for primary curative radiotherapy (either or not combined with chemotherapy or hyperthermia) No previous surgery to the Cervix No previous radiation to the Cervix The patient is willing and capable to comply with study procedures 18 years or older Written informed consent before patient registration Exclusion criteria Recent (< 3 months) myocardial infarction Uncontrolled infectious disease Pregnant or breast feeding and/or not willing to take adequate contraceptive measures during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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 imaging<br>injection with [18F] HX4 and PET imaging at baseline and after 20 Gy radiotherapy | Other: injection with [18F] HX4 and PET imaging<br>* A standard clinical [18F]FDG PET-CT will be performed for the radiotherapy planning. After a minimum time interval of 24 hours, baseline [18F]HX4 PET scans will be performed: Based on the phase I trial1 444 MBq (12 mCi) [18F]HX4 is administrated via a bolus IV injection. The first image acquisition is started together with the administration of [18F]HX4 (30-40 min dynamic). Static scans are acquired at 90 min, 180 min and 240 min p.i<br>* Other names: 3-[18F]fluoro- 2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1- yl)propan-1-ol;|

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 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observation of spatial and temporal stability of [18F] HX4 PET images | Observation of spatial and temporal stability of [18F] HX4 PET images | 2 year | 
| Correlations with Complete Remission rates at 3 months restaging evaluation | Correlations with Complete Remission rates at 3 months restaging evaluation | 2 year | 
| Image quality of [18F] HX4-PET at different time points | Image quality of [18F] HX4-PET at different time points | 2 year | 
| Kinetic analysis of HX4 | Kinetic analysis of HX4 | 2 year | 
| Correlation of hypoxia imaging with blood hypoxia markers (osteopontin, circulating CA-IX) | Correlation of hypoxia imaging with blood hypoxia markers (osteopontin, circulating CA-IX) | 2 year | 
| Correlation of hypoxia imaging with tumor tissue biomarkers (HPV, CA-IX, VEGF, EGFR, CD44, HIF-1α, mir-210) and autophagy related genes | Correlation of hypoxia imaging with tumor tissue biomarkers (HPV, CA-IX, VEGF, EGFR, CD44, HIF-1α, mir-210) and autophagy related genes | 2 year | 
| Spatial correlation of [18F] HX4-PET with [18F] FDG PET pre-treatment | Spatial correlation of [18F] HX4-PET with [18F] FDG PET pre-treatment | 2 year | 
| Spatial correlation of [18F] HX4-PET with [18F] FDG PET three months after treatment | Spatial correlation of [18F] HX4-PET with [18F] FDG PET three months after treatment | 2 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervix cancer, [18F] HX4 PET imaging, hypoxia, phase II trial