Predicting Sites of Tumour Progression in the Invasive Margin of Glioblastomas (PRaM-GBM Study)

High Grade Glioma Clinical Trial

— PRaM-GBM  

Official title:

Predicting Sites of Tumour Progression in the Invasive Margin of Glioblastomas (PRaM-GBM Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03294434
• Other study ID #: PRaM-GBM
• Status: Active, not recruiting
• Start date: March 2, 2017
• Est. completion date: September 30, 2022

Study information

• Verified date: December 2021
• Source: Cambridge University Hospitals NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Brain tumours are the leading cause of cancer deaths in children, men under the age of 45 and women under the age of 25. Glioblastoma is the most common and most malignant primary tumour. The predominant treatment is surgical removal of the tumour followed by radiotherapy. Sadly the majority of patients given this treatment develop recurrent and progressive disease. Better understanding of the invasive margin might improve outcomes by facilitating more complete surgical resection beyond the traditional contrast enhancing margins. Diffusion tensor MRI (DTI) is an imaging technique which may be able to predict the site of tumour recurrence. DTI has previously been shown to identify regions, which have been confirmed with biopsies, to be areas of invasive tumours and are present before progression is seen with an MRI. The primary aim of this study is to qualify an imaging biomarker that can be applied at initial presentation, that can accurately predict the site of where glioblastomas will progress after treatment and allow personalisation of both radiotherapy and surgical targets.

Description:

This is a multicentre, prospective longitudinal observational cohort study in patients with high grade glioma, who have surgery planned to remove >90% of the tumour, and subsequent radical radiotherapy with concomitant tomozolomide. The purpose of this study is to establish a model using DTI that can accurately predict the site of where glioblastomas will progress after treatment. This study aims to validate the use of DTI as a biomarker across multiple centres to develop analysis methods that could be used in the future to personalise radiotherapy treatment volumes, and potentially surgical targets. Patients will be given a DTI-MRI both prior to the operation and prior to radiotherapy. Clinical MRIs will take place according to standard guidelines. Whilst the study is open patients will participate in the study until death. Once a total of 70 patients from the first 90 have shown true progression patients will participate in the study for a minimum of 6 months from the beginning of radiotherapy. This study will be conducted in 6-10 NHS centres, where 120 patients will be recruited, patients who are withdrawn will be replaced.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 139
• Est. completion date: September 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Have given written informed consent to participate
• Assessed by a neuroscience MDT to have a high grade glioma on imaging, OR if in the opinion of the CI, with guidance from the local PI that all relevant and appropriate members of a multidisciplinary team agree a high grade glioma diagnosis;
• Considered suitable for radical radiotherapy (60 Gy) with concomitant chemotherapy (Stupp Regime);
• WHO PS 0 or 1 (see Appendix 3);
• Age =16;
• Patient suitable for tumour resection where the treating neurosurgeon feels that >90% of the enhancing tumour will be resected;

Exclusion Criteria:

• Patients who are participating in trials involving investigational treatments
• Patients who are unsuitable for a contrast-enhanced MRI will be excluded. Such

clinical problems include, but are not limited to:

• MR unsafe metallic implants;
• Claustrophobia;
• Allergy to gadolinium contrast agent;
• History of severe renal impairment.
• Patients unable to provide written informed consent
• PET sub-study only: Pregnant women

Related Conditions & MeSH terms

• Glioblastoma
• High Grade Glioma

Intervention

Other:
• Diffusion tensor Imaging (DTI)
Diffusion tensor Imaging (DTI) is a technique sensitive to the ordered diffusion of water along white matter tracts and can detect subtle disruption. A diffusion tensor signature method was developed that splits the tensor information into isotropic and anisotropic diffusion components. This can differentiate regions of pure tumour from invaded white matter.

Locations

Country	Name	City	State
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge

Sponsors (4)

Lead Sponsor	Collaborator
CCTU- Cancer Theme	Cambridge University Hospitals NHS Foundation Trust, Cancer Research UK, Experimental Cancer Medicine Centres

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Difference of area highlighted by amino-acid PET and DTI-MRI	Investigate the relationship between amino-acid PET, area of surgical resection and the area highlighted by DTI-MRI	18 months
Other	Number of amino-acid PET only image guided biopsies taken from patients	Investigate the feasibility of taking image-guided biopsies from patients in the region outside of the area with increased amino-acid PET uptake	18 months
Other	Site of glioblastoma true progression correctly predicted from pre-operative imaging by a region that is predicted by the DTI abnormality outside of the area of increased uptake to amino-acid on PET	Explore the extent of invasive disease (from DTI/perfusion) that is likely to be left following surgery by assessing potential resected tumour using amino acid PET	18 months
Primary	Site of glioblastoma true progression correctly predicted by DTI scan	Assess the diagnostic accuracy of DTI at pre-surgery or/and pre-radiotherapy as a biomarker to predict site of glioblastoma progression	18 months
Secondary	Accuracy of DTI as a biomarker	Explore difference of DTI performed pre-surgery and pre-radiotherapy to predict the site of glioblastoma progression	18 months
Secondary	Perfusion imaging	Investigate dynamic susceptibility imaging to measure rCBV of the invasive margin to improve the accuracy of the DTI biomarker.	18 months
Secondary	Time to progression	Investigate if pattern of invasion can predict time to progression	18 months
Secondary	Extent of resection and volume of tumour that remains post-surgery by standard imaging and DTI	Determine the effect of resection on the invasive margin as determined by DTI	18 months
Secondary	Radiotherapy dose according to DTI-defined invasive region	Retrospectively compare dose of radiotherapy using the DTI-defined invasive region receives with conventional radiotherapy plans	18 months