Oxygen Enhanced MRI Measurement in Head and Neck Cancer: Validation and Efficacy of Response.

This is a prospective pilot study to investigate the potential clinical value of oxygen-enhanced magnetic resonance (OE-MRI) biomarkers in head and neck radiotherapy.

Study Overview

• Status: Unknown
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Diagnostic test: MRI scan

Detailed Description

This is a prospective pilot study funded by the NIHR. Healthy participants and patients will be recruited in The Christie NHS Foundation Trust and will be asked to undergo oxygen-enhanced magnetic resonance imaging (OE-MRI) and dynamic contrast-enhanced MRI (DCE-MRI). This study builds on the work recently been completed in lung cancer. Clinical data will be collected from patients notes.

Tumour hypoxia is common in solid tumours and associated with poor response to radiotherapy, poor loco-regional control and survival outcomes in head and neck cancer. There is a need to develop non-invasive tests that can measure tumour hypoxia to improve radiotherapy for these patients. The study will involve 3 components:

1. Reproducibility and feasibility: The reproducibility of OE-MRI in head and neck cancer is unknown. Ten healthy participants will be asked to undergo two baseline OE-MRI scans with either nasal cannula or facial mask to breathe air and oxygen throughout. The order of which non-invasive breathing method will be used first will be randomized.

   Following this initial pilot OE-MRI will be tested in 30 patients with solid head and neck tumours. To assess reproducibility in patients 2 OE-MRI will be performed at baseline.

2. Effect of radiotherapy on tumour and normal tissue: OE-MRI and DCE-MRI signals will be measured at baseline before standard radiotherapy treatment begins and at the end of week 2 week and week 4 following the start of radiotherapy. Comparison of hypoxia measurements will be taken.
3. Biological validation: All 30 patients will undergo a diagnostic biopsy as standard of care at their local hospital. Tissue samples will be requested and multi-gene hypoxia signatures will be tested. OE-MRI signals will be compared with tissue sample from the same patient and the presence of changes in tumour known to be associated with hypoxia will be analysed.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sally Falk; Phone Number: 8318 0044 161 446 8318; Email: sally.falk@christie.nhs.uk
• Study Contact Backup: Name: Christina Hague; Phone Number: 8318 0044 161 446 8318; Email: christina.hague@christie.nhs.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 18 or over
2. Able to receive and understand verbal and written information regarding the study and given written informed consent
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
4. Adequate renal function: Calculated creatinine clearance (Cockcroft-Gault) ≥30mL/min
5. Be able to lie comfortably on back for up to 1 hour
6. Be able to tolerate a thermoplastic shell

7. Female patients must meet one of the following criteria:

   i. Postmenopausal for a minimum of one year ii. Surgically sterile iii. Not pregnant, confirmed by B-HCG blood test. iv. Not breastfeeding

8. Cohort A (healthy participants): Up to 10 will be recruited to validate the use of nasal cannula
9. Cohort B (patients): Any patient with HNSCC who is due to start definitive radiotherapy +/- chemotherapy. Up to 30 will be recruited. Each patient prior to recruitment will undergo a diagnostic biopsy at their local hospital as standard of care. The formalin fixed paraffin embedded (FFPE) tumour biopsy sample blocks will be requested from each site and stored in the Manchester Cancer Research Centre (MRCR) and tested for a multi-gene signature.

Exclusion Criteria:

Healthy volunteers or patients with any contraindications to MRI scanning (i.e heart valve replacement, pacemaker, metal implants not approved for MRI, neurostimulators), history of contrast (Gadolinium) allergy or pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MRI scan; 10 healthy participants will be asked to undergo two baseline OE-MRI scans with either nasal cannula or facial mask to breathe air and oxygen throughout. Following this initial pilot, OE-MRI will be tested in 30 patients with solid head and neck tumours.	Diagnostic test: MRI scan; Additional imaging using MRI scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of hypoxia in head and neck squamous cell cancer using oxygen enhanced Magnetic resonance imaging (using a range of different MR sequences)	Assessment of hypoxia in head and neck squamous cell cancer using oxygen enhanced Magnetic resonance imaging (using a range of different MR sequences)	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimal MRI sequence to image participants with head and neck cancer, based on tumour and organ at risk visualisation.	Optimal MRI sequence to image participants with head and neck cancer, based on tumour and organ at risk visualisation.	3 years
Treatment response in a number of participants with head and neck cancer treated with radiotherapy +/- systemic therapy	Treatment response in a number of participants with head and neck cancer treated with radiotherapy +/- systemic therapy	3 years
Treatment related toxicities in a number of participants with head and neck cancer as assessed during and after treatment completion	Treatment related toxicities in a number of participants with head and neck cancer as assessed during and after treatment completion	3 years
Survival outcomes in a number of participants treated with radiotherapy +/- systemic therapy for head and neck cancer	Survival outcomes in a number of participants treated with radiotherapy +/- systemic therapy for head and neck cancer	3 years

Collaborators and Investigators

• Sponsor: Sally Falk
• Collaborators: University of Manchester
• Investigators: Principal Investigator: James O'Connor, University of Manchester

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2018
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): December 31, 2021

Study Registration Dates

• First Submitted: May 3, 2018
• First Submitted That Met QC Criteria: August 23, 2018
• First Posted (ACTUAL): August 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 24, 2018
• Last Update Submitted That Met QC Criteria: August 23, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: magnetic resonance imaging; radiotherapy; head and neck
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms
• Other Study ID Numbers: 18_RADIO_133

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No