Study of the Capacity of the MRI Spectroscopy to Define the Tumor Area Enriched in Glioblastoma Stem Cells. Proof of Concept Study

Study Overview
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Brief Summary
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This is a prospective biomedical study of interventional type which includes 16 patients on 52 months (24 months of inclusion and 28 months of follow up). This pilot study, combining a metabolic imaging approach (Proton Magnetic Resonance Spectroscopy = 1HMRSI) and a biological one, will be performed in patients harbouring a Glioblastoma (GBM)to determine whether MRI markers of aggressiveness (CNI2) are associated with specific biological patterns as regards to GBMSC (GBM contains tumor stem cell). In the first part of the study, patients with radiological criteria of GBM amenable to surgical resection will be included ; pre-operative multimodal MRI scans will be done and all data acquired (including H1MRS and DTI data) will be integrated in the image-guided surgical device (ie neuronavigation system) to be used intraoperatively. During tumor resection, tissue samples will be individualized, based on their multimodal imaging characteristics and sent to the radiobiology laboratory INSERM for biological analysis. After surgery, patient will be treated by the standard radio-chemotherapy stupp protocol and will be followed according to standard practices; multimodal MRI will be performed every 2 months during the first year and then every 3 months until progression.

Official Title
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Study of the Capacity of the MRI Spectroscopy to Define the Tumor Area Enriched in Glioblastoma Stem Cells. Proof of Concept Study

Conditions
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Glioblastoma

Intervention / Treatment
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* Procedure: Surgery (based on preoperative multimodal MRI) followed by the standard radio-chemotherapy stupp protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First part of the study (Surgery and Imagery): Surgical indication for patients who present radiological criteria of glioblastoma. Patient who are ≥18 years old Patient must have performance status between 0 and 2 on the ECOG Performance Scale Life expectancy ≥ 3 months Patient affiliated to social security regimen Patient has voluntarily agreed to participate by giving written informed consent for the first part of the study. Second part of the study (Treatment and Biology): Histologically confirmed glioblastoma Patient must have performance status between 0 and 2 on the ECOG Performance Scale or 3 only is due to motor deficit. Life expectancy ≥ 3 months Patient affiliated to social security regimen Patient has voluntarily agreed to participate by giving written informed consent for the second part of the study. Exclusion Criteria: First part of the study (Surgery and Imagery): Patients who are not allowed to perform an MRI Spectroscopic exam whose results are not contributive Pregnant or nursing patient, Patients under law protection Patient who presents conditions that would interfere with cooperation with the requirements of the trial. Patient who presents medical, severe or chronic biological or psychiatric conditions not allowing his enrolment in the study, according to the investigator's opinion Second part of the study (Treatment and Biology): 1.Biological material received in the lab more than 48 hours after surgery.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgery and radio-chemotherapy<br>Surgery (on the basis of all preoperative multimodal MRI) followed by standard radio-chemotherapy stupp protocol | Procedure: Surgery (based on preoperative multimodal MRI) followed by the standard radio-chemotherapy stupp protocol<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biologic analysis of the GBM resected samples for the capacity to form neurospheres in vitro | comparison CNI2 versus nCNI areas on the capacity to form neurospheres (yes or no) in vitro in stem cells medium up to 5 passages. | 4,5 years | 
| Biologic analysis of the GBM resected samples on the RNA expression of 5 stem cells markers | comparison CNI2 versus nCNI areas on the following criteria : scoring from 0 to 5 according to the RNA expression of 5 stem cells markers (CD133, Nestine, Sox2, Olig2 and Musashi) | 4,5 years | 
| Biologic analysis of the GBM resected samples for their capacity to form invasive brain tumor after orthotopic implantation of the cells in nude mice |  | 4,5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression | The time to progression is defined as the time from surgery until progression | 4,5 years | 
| Overall survival | The overall survival is defined as the time from surgery until death from any cause or last of follow-up news (censored data) | 4,5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioblastoma, Spectroscopy, MRI, Glioma stem cells, Surgery, Radioresistance