Condition category
Cancer
Date applied
07/08/2017
Date assigned
07/08/2017
Last edited
08/08/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

Contact information

Type

Scientific

Primary contact

Ms Stasya Ng

ORCID ID

Contact details

IMAGO Trial Office
Oncology Clinical Trials Office
Department of Oncology
Old Road Campus Research Building
Roosevelt Drive
Headington
Oxford
OX3 7DQ
United Kingdom

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

Specialty: Cancer, Primary sub-specialty: Brain Cancer; UKCRC code/ Disease: Cancer/ Malignant neoplasms of eye, brain and other parts of central nervous system

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 measures

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

30/11/2018

Reason abandoned

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

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

14/09/2017

Recruitment end date

31/07/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Churchill Hospital
Old Road Headington
Oxford
OX3 7LE
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Joint Research Office
Block 60
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
United Kingdom

Sponsor type

University/education

Website

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

30/11/2019

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

08/08/2017: Internal edits.