Bio-CHECC: Biomarkers for Clinical Hypoxia Evaluation in Cervical Cancer

Sponsor

University of Manchester (Other)

Overall Status

Recruiting

CT.gov ID

NCT05029258

Collaborator

The Christie NHS Foundation Trust (Other)

Enrollment

Location

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer	Procedure: Biopsy of tumour Diagnostic Test: MRI scans

Study Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Biomarkers for Clinical Hypoxia Evaluation in Cervical Cancer

Actual Study Start Date :

Dec 10, 2020

Anticipated Primary Completion Date :

Dec 10, 2022

Anticipated Study Completion Date :

Dec 10, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Locally advanced cervical cancer patients treated with standard of care chemoradiation

Procedure: Biopsy of tumour

Cervical tumour biopsy during treatment. This will be used for gene expression (RNA) analysis against a hypoxia associated gene signature.

Diagnostic Test: MRI scans

Multiple magnetic resonance imaging (MRI) scans before and during treatment using oxygen enhanced (OE) / tissues oxygen level dependent (TOLD) sequence

Outcome Measures

Primary Outcome Measures

MRI derived hypoxia scores on 20 participants [2 years]
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.
Gene signature derived hypoxia scores on the same 20 participants. [2 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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