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

Not Applicable

Completed

• Conditions: Glioblastoma
• Interventions: Procedure: Surgery (based on preoperative multimodal MRI) followed by the standard radio-chemotherapy stupp protocol

• Registration Number: NCT01872221
• Lead Sponsor: Institut Claudius Regaud

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05
• Study First Submitted: 2013-05-07
• Study First Submitted QC: 2013-06-03
• Study First Posted: 2013-06-07
• Primary Completion: 2018-04
• Study Completion: 2018-04
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-24
• Last Update Posted: 2018-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

First part of the study (Surgery and Imagery):

1. Surgical indication for patients who present radiological criteria of glioblastoma.
2. Patient who are ≥18 years old
3. Patient must have performance status between 0 and 2 on the ECOG Performance Scale
4. Life expectancy ≥ 3 months
5. Patient affiliated to social security regimen
6. 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):

1. Histologically confirmed glioblastoma
2. Patient must have performance status between 0 and 2 on the ECOG Performance Scale or 3 only is due to motor deficit.
3. Life expectancy ≥ 3 months
4. Patient affiliated to social security regimen
5. 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):

1. Patients who are not allowed to perform an MRI
2. Spectroscopic exam whose results are not contributive
3. Pregnant or nursing patient,
4. Patients under law protection
5. Patient who presents conditions that would interfere with cooperation with the requirements of the trial.
6. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Surgery and radio-chemotherapy	Surgery (based on preoperative multimodal MRI) followed by the standard radio-chemotherapy stupp protocol	Surgery (on the basis of all preoperative multimodal MRI) followed by standard radio-chemotherapy stupp protocol

Primary Outcome Measures

Name	Time	Method
Biologic analysis of the GBM resected samples for the capacity to form neurospheres in vitro	4,5 years	comparison CNI2 versus nCNI areas on the capacity to form neurospheres (yes or no) in vitro in stem cells medium up to 5 passages.
Biologic analysis of the GBM resected samples on the RNA expression of 5 stem cells markers	4,5 years	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)
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

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

Trial Locations

Locations (2)

Institut Claudius REGAUD; 🇫🇷 Toulouse, France

CHU Rangueil; 🇫🇷 Toulouse, France