Plain English Summary
Background and study aims
Several studies have demonstrated that acidity is greater within tumours that in normal tissue. This effect is predominantly driven by the hypoxic (low oxygen) environment in the tumour cells, and the build-up of lactic/carboxylic acid as the cells generate energy in the absence of oxygen. Extracellular acidity (outside cells) has been linked to increased tumour invasion and angiogenesis (blood vessel formation), reduced immune function and also resistance to radiation and systemic cytotoxic (anti-cancer drug) treatment. Chemical exchange saturation transfer (CEST) MRI is a non-invasive imaging technique that can give a readout of tissue pH (acidity). Besides pH there is evidence that this technique is also sensitive to protein concentration in tumours. This technique is already being assessed in stroke patients to aid the detection of areas with restricted blood supply and there is also a preclinical program in Oxford to develop this technique to evaluate tumours. The main aim of this study is to evaluate images obtained from CEST MRI in patients with glioblastoma, a type of brain cancer. The CEST-MRI data will also be compared with arterial spin labelling (ASL) perfusion MRI (a non-invasive imaging technique which assesses water and nutrient exchange) and tissue-based testing including pH, protein content and hypoxia markers.
Who can participate?
Patients aged 18 or over with glioblastoma who are scheduled for surgery
What does the study involve?
Participants undergo a CEST-MRI scan and ASL Perfusion MRI scan in addition to their standard care anatomical MRI scan. These may be repeated at the next standard care imaging visit if there are concerns over the time period between imaging and surgery. At surgery, biopsies (tissue samples) are taken for analysis. No visits additional to standard care are anticipated.
What are the possible benefits and risks of participating?
There is not expected to be a clinical benefit to those taking part in the study. There are no known risks or side effects to having a MRI, after proper safety considerations have been addressed. MRI is safe and non-invasive and does not involve any ionising radiation (x-rays). Participants are asked safety questions to help determine if they are able to take part. Some people find that the scanner makes them feel uncomfortable (because they have to keep still for a long time), gives them vertigo (dizziness) or claustrophobic (nervous in small spaces). Such feelings go away once the participant is outside the scanner and there are no after-effects of having a MRI scan. The main risk associated with biopsy of glioblastoma is haemorrhage (bleeding). However in this setting, biopsy of the tumour during surgery should not carry any increased risk as the participant’s tumour will be operated on immediately afterward.
Where is the study run from?
Churchill Hospital (UK)
When is the study starting and how long is it expected to run for?
February 2017 to November 2018
Who is funding the study?
Cancer Research UK
Who is the main contact?
Ms Stasya Ng
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
35083
Study information
Scientific title
A single-arm exploratory study examining the feasibility of imaging glioblastoma pH using CEST-MRI
Acronym
Study hypothesis
Several studies have demonstrated that acidity within tumours is greater that in normal tissue. This effect is predominantly driven by the hypoxic (low oxygen) environment in the tumour cells, and accumulation of lactic/carboxylic acid as the cells generate energy in the absence of oxygen. Extracellular acidity has been linked to increased tumour invasion and angiogenesis (blood vessel formation), reduced immune function and also resistance to radiation and systemic cytotoxic (anti-cancer drug) therapy.
Chemical exchange saturation transfer (CEST) MRI is a non-invasive imaging technique that can give a readout of tissue pH (acidity). Besides pH there is evidence that this technique is also sensitive to protein concentration in tumour models. This technique is already being assessed in stroke patients to aid the detection of areas with restricted blood supply and there is also a preclinical program in Oxford to develop this technique to evaluate tumours.
The primary objective for this study is to evaluate CEST contrast image obtained from CEST MRI in glioblastoma, a type of brain cancer. As part of this study there are also several exploratory objectives in which the CEST-MRI signature will be correlated with tissue perfusion using arterial spin labelling/ASL perfusion MRI (a non-invasive imaging technique which assesses tissue perfusion/the extent of water and nutrient exchange with tissue) and tissue based testing including pH, protein content and immunohistochemistry to assess for hypoxia markers.
Ethics approval
South Central- Oxford A Research Ethics Committee, 18/07/2017, ref: 17/SC/0304
Study design
Non-randomised; Interventional; Design type: Diagnosis, Process of Care, Imaging
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Diagnostic
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Brain Cancer
Intervention
Study participants (previously untreated glioblastoma patients for resection/debulking surgery) will undergo a CEST-MRI scan and ASL Perfusion MRI scan in addition to their standard care anatomical MRI scan. These may be repeated at the next standard care imaging visit if there are concerns over the time period between imaging and surgery. At surgery, biopsies will be taken for analysis prior to tumour resection/debulking. No visits additional to standard care are anticipated.
Intervention type
Other
Phase
Drug names
Primary outcome measure
pH-weighted CEST MRI signal, assessed using amide proton transfer ratio analysis, taken at the patient’s imaging visit
Secondary outcome measures
1. Protein levels obtained from tissue-based assay using biopsies obtained on the surgery date
2. pH levels obtained from tissue-based assay using biopsies obtained on the surgery date
3. Hypoxia markers obtained from immunohistochemistry using biopsies obtained on the surgery date
4. Cerebral blood flow and bolus arrival time from ASL MRI perfusion scan, taken at the patient’s imaging visit
Overall trial start date
23/02/2017
Overall trial end date
30/06/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Participant is willing, capable of cooperating with the protocol and able to give informed consent for participation in the study
2. Male or female, aged 18 years or above
3. Diagnosed with glioblastoma and scheduled for neurosurgical resection or debulking
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 20; UK Sample Size: 20
Participant exclusion criteria
Current exclusion criteria as of 16/02/2018:
1. Intolerant of MRI brain (for example: claustrophobia)
2. MRI brain contraindicated (for example: implanted electric and electronic devices, heart pacemakers, insulin pumps, implanted hearing aids, neurostimulators, intracranial metal clips, metallic bodies in the eye)
3. Neoadjuvant chemotherapy/radiotherapy treatment for glioblastoma which would interfere with the interpretation of trial results
4. Pregnancy
5. Other psychological, social or medical condition that the investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results
Previous exclusion criteria:
1. Intolerant of MRI brain (for example: claustrophobia)
2. MRI brain contraindicated (for example: implanted electric and electronic devices, heart pacemakers, insulin pumps, implanted hearing aids, neurostimulators, intracranial metal clips, metallic bodies in the eye)
3. Prior treatment for glioblastoma
4. Pregnancy
5. Other psychological, social or medical condition that the investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results
Recruitment start date
24/10/2017
Recruitment end date
31/05/2019
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom
Funders
Funder type
Charity
Funder name
Cancer Research UK
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
The intention is to publish this research in a specialist peer reviewed scientific journal.
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
30/06/2020
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list