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
• Sponsor: Center Eugene Marquis
• Collaborator: Rennes University Hospital
• Information provided by: Center Eugene Marquis

Study Description

Brief 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.

Condition or disease	Intervention/treatment
Glioblastoma	Drug: Temozolomide; Radiation: Radiation Therapy

Detailed 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).

Study Design

• Study Type: Observational
• Actual Enrollment: 300 participants
• Time Perspective: Prospective
• 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

Groups and Cohorts

Group/Cohort	Intervention/treatment
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.	Drug: Temozolomide; According to sites procedures; Other Name: Temodal (brand name).; Radiation: Radiation Therapy; According to sites procedures; Other Name: Radiotherapy

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. Progression-Free Survival [ Time Frame: 12 months ]

Biospecimen Retention:   Samples With DNA

Freezed or/and parffine embedded tumor samples.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

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

Criteria

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

Contacts and Locations

Locations

France

CHRU Hautepierre

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

Sponsors and Collaborators

Center Eugene Marquis

Rennes University Hospital

More Information

Publications:

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.

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.

• Responsible Party: Veronique QUILLIEN, MD, Center Eugene Marquis
• ClinicalTrials.gov Identifier: NCT01345370
• Other Study ID Numbers: ECOM-Glioblastome
• First Posted: May 2, 2011
• Last Update Posted: January 29, 2016
• Last Verified: January 2016

Keywords provided by Center Eugene Marquis:

Glioblastoma

Additional relevant MeSH terms:

Glioblastoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Temozolomide; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents