Non Invasive Detection of IDH1/2 Mutation in Gliomas (IDASPE)

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

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.

Study Overview

• Status: Unknown
• 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

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:

1. longitudinal analysis Spectro-MRI overtime (12 months) correlation with radiological evolution and the response to treatment (group 2: 15 patients)
2. Differentiation of tumor recurrence from radiation induced changes
3. Confrontation of Spectro-MRI, D-2HG dosages and IDH mutation detection from plasma DNA, and elaboration of a combined score of prediction

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Groupe Hospitalier Pitie-Salpetriere
    • Contact: Marc Sanson, MD, PhD; Phone Number: +331 42 16 03 91

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. Affiliation to a social security system
2. Patient≥ 18 years old
3. Written informed consent

4. 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)
5. Evaluable tumoral mass min diameter >2 cm (FLAIR)
6. PKPS > 60

Exclusion criteria

1. Contra-indication to MRI
2. Patient unable to give an written Informed Consent
3. Patient under guardianship or deprived of freedom
4. For group 2: patient already included in group 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Marc Sanson, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Anticipated): April 1, 2018
• Study Completion (Anticipated): April 1, 2018

Study Registration Dates

• First Submitted: April 27, 2015
• First Submitted That Met QC Criteria: November 3, 2015
• First Posted (Estimate): November 5, 2015

Study Record Updates

• Last Update Posted (Actual): September 20, 2017
• Last Update Submitted That Met QC Criteria: September 19, 2017
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Glioma; IDH1/IDH2 mutation; Spectroscopy MRI; D-2-hydroxyglutarate; Free circulating DNA
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: P120141