Non Invasive IDentification of Gliomas With IDH1 Mutation

NCT ID: NCT01703962

Last Updated: 2021-08-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 6 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-03-14
• Study Completion Date: 2014-03-20

Brief Summary

The recurrent mutation IDH1Arg132His leads to the cellular accumulation of D-2-hydroxyglutarate (2-HG), thus representing a diagnostic marker (this change is almost specific for gliomas) and prognostic (mutated gliomas have longer survival) of interest.

The main objective is to identify the patients with IDH1 mutated glioma by three complementary approaches -genetic (identification of IDH1 mutation in plasmatic DNA), biochemical (2-HG dosage in the urine of patients) and radiological (2-HG

Detailed Description

Our preliminary results indicate an extremely high amount of D-2HG in gliomas and CSF of the patients, and therefore the possibility to detect its presence by spectro-MRI, and to establish a non-invasive diagnosis of glioma with IDH1 mutation. Our goal is to identify and quantify by high-field MRI spectroscopy the presence of D-2HG to identify gliomas with IDH1 mutation. In parallel, we developed a technique for selective amplification of the mutated form of IDH1 (COLD PCR): by combining this technique with digital PCR, we already are able to detect IDH1 mutation from free plasma DNA with a sensitivity of 58% and a specificity of 100%. At the same time we have shown that D-2HG levels in urine of patients correlate with the status of the tumor IDH1.

The main objective is to identify using this triple approach (detection of the mutation on plasma DNA detection, detection of urinary D-2HG, detection of tumor D-2HG by spectro-MRI) patients with IDH1arg132His mutation, the secondary objective is to evaluate the value of these markers for patients follow-up and for differentiating recurrence from treatment induced damage. 40 patients with grade II and grade III gliomas (20 mutated, 20 non mutated) will be included and followed up for one year (five measurements are planned).

The first interest is diagnostic: the presence of the IDH1Arg132His mutation allows the diagnosis of glioma. This information is particularly valuable in patients not amenable to biopsy, because of the location of the tumor considered at risk, the general condition of the patient or the co-morbidities and medications. We hope also with these parameters to better monitor patient's follow-up, and to have a new method to differentiate tumor recurrence and radionecrosis or post-radiation leukoencephalopathy.

Conditions

Non Invasive Diagnosis of Glioma

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients with IDH1 R132H or wild type IDH1/IDH2 glioma

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Affiliated to Health Insurance regimen (sécurité sociale)
• Patient of 18 years or more
• written informed consent
• Glioma grade II or III histologically proven
• Frozen samples available
• Known status IDH1/IDH2
• Presence of a measurable residual tumor (> 2 cm in diameter FLAIR)
• Karnofsky Performance Status (KPS)> 60

Exclusion Criteria

• Contraindication to MRI *
• The rare patients with IDH2 mutation or with non Arg132His IDH1 mutation will be excluded
• Inability to provide informed consent
• Patient under guardianship or deprived of liberty by court

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc SANSON, MDPhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

GH Pitié-Salpêtrière, 47 Bd de l'Hopital,

Paris, Sélectionner..., France

Countries

France

References

Branzoli F, Liserre R, Deelchand DK, Poliani PL, Bielle F, Nichelli L, Sanson M, Lehericy S, Marjanska M. Neurochemical Differences between 1p/19q Codeleted and Noncodeleted IDH-mutant Gliomas by in Vivo MR Spectroscopy. Radiology. 2023 Sep;308(3):e223255. doi: 10.1148/radiol.223255.

Reference Type: DERIVED

PMID: 37668523 (View on PubMed)

Other Identifiers

2011-A01356-35

Identifier Type: REGISTRY

Identifier Source: secondary_id

C11-28

Identifier Type: -

Identifier Source: org_study_id