Biomarkers for Clinical Hypoxia Evaluation in Cervical Cancer

Study Overview
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Brief Summary
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Patients with locally advanced cervical cancer (LACC) are primarily treated with radiotherapy +/- chemotherapy however 5-year survival rates are <60% with significant treatment toxicity. Hypoxia is a well-known radioresistant component of solid tumours such as cervical cancer and hypoxia modification therapies have demonstrated immense promise in treating such tumours. A major factor in determining a successful outcome with hypoxia modification is appropriate patient selection as it is hypoxic tumours that receive the most benefit from hypoxia modifying therapies. To date there is no validated hypoxia biomarker to stratify patients for therapy in cervical cancer in clinical use. This project offers a unique opportunity to examine both genetic and imaging biomarkers to optimise patient stratification when receiving curative radiotherapy for cervical cancer.

Official Title
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Biomarkers for Clinical Hypoxia Evaluation in Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Procedure: Biopsy of tumour
* Diagnostic Test: MRI scans


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients must have a histologically confirmed diagnosis of cervical cancer Diagnostic/pre-treatment biopsy available Patients must be suitable for standard radiotherapy and brachytherapy Age greater than or equal to 18 years; no upper age limit Performance status - ECOG 0-2 (Refer to appendix 1) Women of childbearing age MUST have a negative pregnancy test prior to study entry and be using an adequate contraception method Before participant registration, written informed consent must be given according to GCP and national regulations. Exclusion criteria: Participants deemed unsuitable for a biopsy (during or following radiotherapy) in the opinion of the treating oncologist. Patients with cardiac pacemakers, cochlear implants, intraocular foreign bodies or any other MR contraindication Patients with a hip replacement Patients with a known history of allergic reaction to gadolinium-based contrast agent Any contraindications to Hyoscine Butylbromide (Buscopan) Any patient taking ACE inhibitors. These should be stopped/substituted or they are a contraindication. Evidence of impaired renal function (eGFR <15 ml/min) Any evidence of severe or uncontrolled systemic diseases which, in the view of the investigator, makes it undesirable for the patient to participate in the study Evidence of significant clinical disorder or laboratory finding which, in the opinion of the investigator makes it undesirable for the patient to participate in the study Any other serious uncontrolled medical conditions Clinical evidence of metastatic disease Any pregnant or lactating woman Any patient with a medical or psychiatric condition that impairs their ability to give informed consent Any patient who is currently involved in, or who has recently been involved in other research

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Locally advanced cervical cancer patients treated with standard of care chemoradiation<br> | Procedure: Biopsy of tumour<br>* Cervical tumour biopsy during treatment. This will be used for gene expression (RNA) analysis against a hypoxia associated gene signature.<br>Diagnostic Test: MRI scans<br>* Multiple magnetic resonance imaging (MRI) scans before and during treatment using oxygen enhanced (OE) / tissues oxygen level dependent (TOLD) sequence<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI derived hypoxia scores on 20 participants | 20 patients will undergo functional imaging (hypoxia MRI) at baseline. Following this, serial measurements will be taken on a weekly basis during the first 5 weeks of chemoradiation. The imaging and biopsy cohorts are the same. | 2 years | 
| Gene signature derived hypoxia scores on the same 20 participants. | Investigators will collect paired biopsies at diagnosis and at brachytherapy in 20 locally advanced cervical cancer patients. The imaging and biopsy cohorts are the same. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoxia, Radiotherapy, Imaging, Gene expression