Comparison of Different Methods to Test MGMT Status in Glioblastoma Patients (ECOM)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by Center Eugene Marquis.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Rennes University Hospital
Information provided by:
Center Eugene Marquis
ClinicalTrials.gov Identifier:
NCT01345370
First received: April 20, 2011
Last updated: April 29, 2011
Last verified: April 2011

April 20, 2011
April 29, 2011
March 2009
December 2011   (final data collection date for primary outcome measure)
Survival of patients according to their MGMT status. [ Time Frame: 12 months after last enrollment ] [ Designated as safety issue: No ]
Predictive MGMT methylation tests values related to mean overall survival.
Same as current
Complete list of historical versions of study NCT01345370 on ClinicalTrials.gov Archive Site
Progression-Free Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Comparison of Different Methods to Test MGMT Status in Glioblastoma Patients
Comparative Assessment of Methods to Analyze MGMT as a Predictive Factor of Response to Temozolomide in Glioblastomas.

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.

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).

Observational
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Freezed or/and parffine embedded tumor samples.

Non-Probability Sample

Patients with glioblastoma, eligible to resection and to a treatment according to the Stupp schedule.

Glioblastoma
  • Drug: Temozolomide
    According to sites procedures
    Other Name: Temodal (brand name).
  • Radiation: Radiation Therapy
    According to sites procedures
    Other Name: Radiotherapy
Stupp protocole
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.
Interventions:
  • Drug: Temozolomide
  • Radiation: Radiation Therapy

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
300
December 2012
December 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
Not Provided
France
 
NCT01345370
ECOM-Glioblastome
No
Veronique QUILLIEN, MD, Center Eugene Marquis
Center Eugene Marquis
Rennes University Hospital
Not Provided
Center Eugene Marquis
April 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP