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
  Purpose

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 Intervention
Glioblastoma
Drug: Temozolomide
Radiation: Radiation Therapy

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Comparative Assessment of Methods to Analyze MGMT as a Predictive Factor of Response to Temozolomide in Glioblastomas.

Resource links provided by NLM:


Further study details as provided by Center Eugene Marquis:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Progression-Free Survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Freezed or/and parffine embedded tumor samples.


Estimated Enrollment: 300
Study Start Date: March 2009
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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).

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01345370

Locations
France
CHRU Hautepierre Recruiting
Strasbourg, Alsace, France, 67
Contact: Natacha ENTZ-WERLE, MD    +33 388 12 83 96    Natacha.Entz-Werle@chru-strasbourg.fr   
Principal Investigator: Natacha ENTZ-WERLE, MD         
CHU de Bordeaux Recruiting
Bordeaux, Aquitaine, France, 33000
Contact: Pierre DUBUS, MD, PhD    +33 557 57 16 80    pierre.dubus@histo.u-bordeaux2.fr   
Principal Investigator: Pierre DUBUS, MD, PhD         
CHU Cote de Nacre Recruiting
Caen, Basse Normandie, France, 14000
Contact: Emmanuele LECHAPT-ZALCMAN, MD    +33 231 06 45 04    lechapt-e@chu-caen.fr   
Principal Investigator: Emmanuele LECHAPT-ZALCMAN, MD         
Center Eugene Marquis Recruiting
Rennes, Brittany, France, 35000
Contact: Veronique QUILLIEN, MD    +33 299 25 31 63    v.quillien@rennes.fnclcc.fr   
Contact: Oussama ZEKRI, PhD    +33 299 25 31 32    o.zekri@rennes.fnclcc.fr   
Principal Investigator: Veronique QUILLIEN, MD         
Sub-Investigator: Thierry LESIMPLE, MD         
Sub-Investigator: Isabelle LECOUILLARD, MD         
Sub-Investigator: Mohamed BEN HASSEL, MD         
CHU La Salpetriere Recruiting
Paris, Ile de France, France, 75000
Contact: Marc SANSON, MD    +33 142 16 03 91    marc.sanson@psl.aphp.fr   
Principal Investigator: Marc SANSON, MD         
CHRU de Lille Recruiting
Lille, Nord Pas-de-Calais, France, 59000
Contact: Fabienne ESCANDE, MD    +33 320 44 61 54    f-escande@chru-lille.fr   
Principal Investigator: Fabienne ESCANDE, MD         
CHU La Timone Recruiting
Marseille, Paca, France, 13000
Contact: Dominique FIGARELLA, MD, PhD       dominique.figarella-branger@univmed.fr   
Principal Investigator: Dominique FIGARELLA, MD, PhD         
CHU de Poitiers Recruiting
Poitiers, Poitou-Charentes, France, 86000
Contact: Lucie KARAYAN-TAPON, MD    +33 549 44 49 88    l.karayan-tapon@chu-poitiers.fr   
Principal Investigator: Lucie KARAYAN-TAPON, MD         
CHU de Grenoble Active, not recruiting
Grenoble, Rhone-Alpes, France, 38000
CHU de Lyon Recruiting
Lyon, Rhone-Alpes, France, 69000
Contact: Francois DUCRAY, MD    +33 427 85 54 60    francois.ducray@chu-lyon.fr   
Principal Investigator: Francois DUCRAY, MD         
Sponsors and Collaborators
Center Eugene Marquis
Rennes University Hospital
  More Information

Publications:
Responsible Party: Veronique QUILLIEN, MD, Center Eugene Marquis
ClinicalTrials.gov Identifier: NCT01345370     History of Changes
Other Study ID Numbers: ECOM-Glioblastome
Study First Received: April 20, 2011
Last Updated: April 29, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 21, 2014