Comparison of Different Methods to Test MGMT Status in Glioblastoma Patients

Glioblastoma Clinical Trial

— ECOM  

Official title:

Comparative Assessment of Methods to Analyze MGMT as a Predictive Factor of Response to Temozolomide in Glioblastomas.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01345370
• Other study ID #: ECOM-Glioblastome
• Status: Completed
• Phase: N/A
• First received: April 20, 2011
• Last updated: January 28, 2016
• Start date: March 2009
• Est. completion date: June 2015

Study information

• Verified date: January 2016
• Source: Center Eugene Marquis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Observational

Clinical Trial Summary

Treatment for newly diagnosed glioblastomas currently involves surgical resection followed by Temozolomide chemotherapy with concomitant radiotherapy, and then 6 cycles of Temozolomide in adjuvant. According to many studies, only those patients not expressing the enzyme repair MGMT benefit from the adjunction of Temozolomide. Therefore, many patients receive unnecessary treatment. The aim of this project is to compare different techniques for analysis of MGMT in order to choose the approach with the best cost/utility ratio, which will allow the selection of patients likely to respond to TMZ chemotherapy during the first course of GBM treatment.

Description:

Treatment for newly diagnosed glioblastomas (GBM) currently involves surgical resection followed by Temozolomide (TMZ) chemotherapy with concomitant radiotherapy, and then 6 cycles of TMZ in adjuvant (Stupp schedule). According to many studies, only those patients not expressing the enzyme repair MGMT benefit from the adjunction of TMZ. Therefore, many patients receive unnecessary treatment at an average cost of about 15,000 euros.

The aim of this project is to compare different techniques for analysis of MGMT in order to choose the approach with the best cost/utility ratio, which will allow the selection of patients likely to respond to TMZ chemotherapy during the first course of GBM treatment. Another aspect of this project is to evaluate the extra cost produced by TMZ treatment, and therefore the expected cost saving in the case of using a reliable predictive factor. This kind of evaluation is of great importance, as the MGMT test status is beginning to appear in the decisional care trees of high-grade gliomas The two main techniques for MGMT analysis are currently immunohistochemistry (IH) and molecular analysis of promoter methylation of the gene. Immunohistochemistry is simple and quick, but there is no consensus about labelling or evaluation of the staining, all of which could lead to variability in results. Studies of promoter methylation are currently performed by the MS-PCR technique, in particular the article published in the N Engl J Med in 2005 showing that only patients with a methylated promoter benefit from TMZ adjunction. This technique appears somewhat rudimentary compared to techniques avoiding subjectivity linked to eye reading of the gel after electrophoresis of PCR products.

In phase one of this multicenter national study, IH, MS-PCR, MethyLight, pyrosequencing and MS-HRM will be compared in a retrospective study on 100 samples (frozen for molecular analysis and paraffin-embedded for IH), taken from patients treated according to the Stupp protocol and with a follow-up of 18 months at least. In phase 2, the two techniques with the best cost/efficacy ratio (based on predictive value, analytical quality and feasibility of the test) will be implemented in all the laboratories according to a standard protocol developed by the referral centre for the tests. The dissemination of quality controls will allow us to check that the same results are obtained from one laboratory to another. In phase 3, samples will be analysed prospectively in the different centres and a medico-economic analysis will be undertaken on the integration of MGMT analysis into the standard care of GBM patients. Two types of analysis will be performed: i) on the costs of the techniques, allowing us in particular to estimate the possible additional clinical cost generated and its effect on the cost of a hospital stay, in order to adjust the charging system, and ii) on alternative care strategies for the patients, with or without screening, leading to improve the target of treatments by TMZ, with the aim of improving the definition of "options and recommendations" (cost-utility analysis).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: June 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Adult, age from 18 to 70

• Pre-surgical diagnosis compatible with a primary or secondary sub-tentorial glioblastoma than can be resected

• No counter-indication to an adjuvant treatment according to the Stupp schedule

• Free written informed consent

Exclusion Criteria:

• Absence of tumor sample available

• Definite histology not related to a glioblastoma or a main oligodendroglioma component

Study Design

Time Perspective: Prospective

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Drug:
• Temozolomide
According to sites procedures

Radiation:
• Radiation Therapy
According to sites procedures

Locations

Country	Name	City	State
France	CHU de Bordeaux	Bordeaux	Aquitaine
France	CHU Cote de Nacre	Caen	Basse Normandie
France	CHU de Grenoble	Grenoble	Rhone-Alpes
France	CHRU de Lille	Lille	Nord Pas-de-Calais
France	CHU de Lyon	Lyon	Rhone-Alpes
France	CHU La Timone	Marseille	Paca
France	CHU La Salpetriere	Paris	Ile de France
France	CHU de Poitiers	Poitiers	Poitou-Charentes
France	Center Eugene Marquis	Rennes	Brittany
France	CHRU Hautepierre	Strasbourg	Alsace

Sponsors (2)

Lead Sponsor	Collaborator
Center Eugene Marquis	Rennes University Hospital

Country where clinical trial is conducted

France, 

References & Publications (2)

Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005 Mar 10;352(10):997-1003. — View Citation

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival of patients according to their MGMT status.	Predictive MGMT methylation tests values related to mean overall survival.	12 months after last enrollment	No
Secondary	Progression-Free Survival		12 months	No