Comparison of Different Methods to Test MGMT Status in Glioblastoma Patients (ECOM)
|ClinicalTrials.gov Identifier: NCT01345370|
Recruitment Status : Completed
First Posted : May 2, 2011
Last Update Posted : January 29, 2016
|Condition or disease||Intervention/treatment|
|Glioblastoma||Drug: Temozolomide Radiation: Radiation Therapy|
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).
|Study Type :||Observational|
|Actual Enrollment :||300 participants|
|Official Title:||Comparative Assessment of Methods to Analyze MGMT as a Predictive Factor of Response to Temozolomide in Glioblastomas.|
|Study Start Date :||March 2009|
|Actual Primary Completion Date :||April 2015|
|Actual Study Completion Date :||June 2015|
All subjects enrolled must be treated according to the Stupp schedule : surgical resection followed by Temozolomide (TMZ) chemotherapy with concomitant radiotherapy, and then 6 cycles of adjuvant Temzolomide.
According to sites procedures
Other Name: Temodal (brand name).
Radiation: Radiation Therapy
According to sites procedures
Other Name: Radiotherapy
- Survival of patients according to their MGMT status. [ Time Frame: 12 months after last enrollment ]Predictive MGMT methylation tests values related to mean overall survival.
- Progression-Free Survival [ Time Frame: 12 months ]
Biospecimen Retention: Samples With DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01345370
|Strasbourg, Alsace, France, 67|
|CHU de Bordeaux|
|Bordeaux, Aquitaine, France, 33000|
|CHU Cote de Nacre|
|Caen, Basse Normandie, France, 14000|
|Center Eugene Marquis|
|Rennes, Brittany, France, 35000|
|CHU La Salpetriere|
|Paris, Ile de France, France, 75000|
|CHRU de Lille|
|Lille, Nord Pas-de-Calais, France, 59000|
|CHU La Timone|
|Marseille, Paca, France, 13000|
|CHU de Poitiers|
|Poitiers, Poitou-Charentes, France, 86000|
|CHU de Grenoble|
|Grenoble, Rhone-Alpes, France, 38000|
|CHU de Lyon|
|Lyon, Rhone-Alpes, France, 69000|