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

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ClinicalTrials.gov Identifier: NCT03294434
Recruitment Status : Recruiting
First Posted : September 27, 2017
Last Update Posted : October 22, 2020
Sponsor:
Collaborators:
Cambridge University Hospitals NHS Foundation Trust
Cancer Research UK
Experimental Cancer Medicine Centre
Information provided by (Responsible Party):
CCTU- Cancer Theme, Cambridge University Hospitals NHS Foundation Trust

Tracking Information
First Submitted Date September 22, 2017
First Posted Date September 27, 2017
Last Update Posted Date October 22, 2020
Actual Study Start Date March 2, 2017
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 22, 2017)
Site of glioblastoma true progression correctly predicted by DTI scan [ Time Frame: 18 months ]
Assess the diagnostic accuracy of DTI at pre-surgery or/and pre-radiotherapy as a biomarker to predict site of glioblastoma progression
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: September 22, 2017)
  • Accuracy of DTI as a biomarker [ Time Frame: 18 months ]
    Explore difference of DTI performed pre-surgery and pre-radiotherapy to predict the site of glioblastoma progression
  • Perfusion imaging [ Time Frame: 18 months ]
    Investigate dynamic susceptibility imaging to measure rCBV of the invasive margin to improve the accuracy of the DTI biomarker.
  • Time to progression [ Time Frame: 18 months ]
    Investigate if pattern of invasion can predict time to progression
  • Extent of resection and volume of tumour that remains post-surgery by standard imaging and DTI [ Time Frame: 18 months ]
    Determine the effect of resection on the invasive margin as determined by DTI
  • Radiotherapy dose according to DTI-defined invasive region [ Time Frame: 18 months ]
    Retrospectively compare dose of radiotherapy using the DTI-defined invasive region receives with conventional radiotherapy plans
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 22, 2017)
  • Difference of area highlighted by amino-acid PET and DTI-MRI [ Time Frame: 18 months ]
    Investigate the relationship between amino-acid PET, area of surgical resection and the area highlighted by DTI-MRI
  • Number of amino-acid PET only image guided biopsies taken from patients [ Time Frame: 18 months ]
    Investigate the feasibility of taking image-guided biopsies from patients in the region outside of the area with increased amino-acid PET uptake
  • 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 [ Time Frame: 18 months ]
    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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Predicting Sites of Tumour Progression in the Invasive Margin of Glioblastomas (PRaM-GBM Study)
Official Title Predicting Sites of Tumour Progression in the Invasive Margin of Glioblastomas (PRaM-GBM Study)
Brief 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.

Detailed 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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Patients that consent to participate in the optional PET sub-study will consent to the collection of additional tissue biopsies to be taken at the time of their standard of care surgery.
Sampling Method Probability Sample
Study Population Male and female patients aged 16 and over with newly diagnosed glioblastomas
Condition 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.
Study Groups/Cohorts High Grade Glioma
Diffusion tensor Imaging (DTI-MRI) scan to be performed pre-operatively and pre-radiotherapy
Intervention: Other: Diffusion tensor Imaging (DTI)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: September 22, 2017)
120
Original Estimated Enrollment Same as current
Estimated Study Completion Date September 30, 2021
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Julia Cook 01223 348091 julia.cook@addenbrookes.nhs.uk
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT03294434
Other Study ID Numbers PRaM-GBM
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party CCTU- Cancer Theme, Cambridge University Hospitals NHS Foundation Trust
Study Sponsor CCTU- Cancer Theme
Collaborators
  • Cambridge University Hospitals NHS Foundation Trust
  • Cancer Research UK
  • Experimental Cancer Medicine Centre
Investigators
Principal Investigator: Stephen Price Cambridge University Hospitals NHS Foundation Trust
PRS Account Cambridge University Hospitals NHS Foundation Trust
Verification Date October 2020