Non Invasive Detection of IDH1/2 Mutation in Gliomas

Study Overview
=================
Brief Summary
-----------------
This trial develops a non invasive diagnostic approach of IDH1 mutated gliomas combining mutation detection from free plasmatic DNA, D-2HG dosage in urine samples, and D-2HG detection by Brain Spectro MRI. In group 1 (25 patients), patients with presumed grade II-III gliomas candidate to surgery will undergo spectro MRI, plasma, urine dosages. Results will then be confronted to tumor mutational status and D-2HG. In group 2 (15 patients), patients with known IDH1 mutation will undergo spectro MRI, plasma, urine dosages overtime in order to correlate results with the response to treatment.

Detailed Description
-----------------
The aim of this trial is to develop and validate a non invasive diagnostic approach of IDH1 mutated gliomas. It will evaluate the specificity and sensitivity of D-2HG detection by Brain Spectro MRI. This approach will be coupled with mutation detection from free plasmatic DNA and D-2HG dosage in urine samples. The primary end-point is the quantification of D-2HG by spectro-MRI, and the correlation with the dosage of D-2HG in the tumor fragment, and the mutational status (group 1: 25 patients). The secondary endpoints include: longitudinal analysis Spectro-MRI overtime (12 months) correlation with radiological evolution and the response to treatment (group 2: 15 patients) Differentiation of tumor recurrence from radiation induced changes Confrontation of Spectro-MRI, D-2HG dosages and IDH mutation detection from plasma DNA, and elaboration of a combined score of prediction

Official Title
-----------------
Non Invasive IDentification of Gliomas With IDH1/2 Mutation by Analysis of Circulating Plasmatic DNA, D-2-hydroxyglutarate Dosage in Biological Liquids and Detection by Brain SPEctro-MRI: Impact for Diagnosis and Follow-up

Conditions
-----------------
Glioma, IDH1/IDH2 Mutation

Intervention / Treatment
-----------------
* Radiation: Spectro-MRI
* Other: Dosage of free circulating plasmatic DNA
* Other: Dosage of D-2HG in the urine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Affiliation to a social security system Patient≥ 18 years old Written informed consent One of the two situations: presumed grade II-III glioma candidate to surgery (group 1) IDH1/IDH2 mutated grade II-III gliomas, candidate to chemotherapy or radiotherapy treatment, or simple follow-up (group 2) Evaluable tumoral mass min diameter >2 cm (FLAIR) PKPS > 60 Exclusion criteria Contra-indication to MRI Patient unable to give an written Informed Consent Patient under guardianship or deprived of freedom For group 2: patient already included in group 1

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IDH1/IDH2<br> | Radiation: Spectro-MRI<br>* Spectro-MRI for D-2HG detection<br>Other: Dosage of free circulating plasmatic DNA<br> <br> Other: Dosage of D-2HG in the urine<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| D-2HG quantified by spectroMRI the measure of the ratio between two pics D-2HG and creatine [Time Frame: 3 months after surgery] [Designated as safety issue: No] | This ratio D-2HG/creatine will be correlated with the dosage obtained in tumor tissue performed within three months after the surgery | 3 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SpectroMRI [Time Frame: evolution over 12 months] [Designated as safety issue: No] | The ratio D-2HG/creatine will be evaluated overtime and correlated with radiological evolution and the response to treatment (group 2: 15 patients) every four months | evolution over 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Glioma, IDH1/IDH2 mutation, Spectroscopy MRI, D-2-hydroxyglutarate, Free circulating DNA