Assessment of MGMT Promoter Methylation in Advanced Ewing Sarcoma Treated With Temozolomide and Irinotecan (MGMTLiberati)

Assessment of MGMT Promoter Methylation and Clinical Benefit From Temozolomide-based Therapy in Ewing Sarcoma Patients

This is a biological study in patients with advanced Ewing Sarcoma who received, according, clinical practice, temozolomide and irinotecan The O6-methylguanine-DNA methyltransferase (MGMT) methylation status, will be correlated with the disease clinical data and with the disease response

Study Overview

• Status: Completed
• Conditions: Ewing Sarcoma Family of Tumors
• Intervention / Treatment: Other: MGMT methylation evaluation

Detailed Description

This is a biological study in patients with advanced Ewing Sarcoma who received, according, clinical practice, temozolomide and irinotecan.

The MGMT methylation status will be correlated with the disease clinical data and with the disease response also in term of metabolic activity (if data will be available) The MGMT methylation analysis will be performed extracting from fresh tumor sample, the DNA on the basis of the standard protocols.

• Study Type: Observational
• Enrollment (Actual): 82

Contacts and Locations

• Study Contact: Name: Emanuela Palmerini, MD; Phone Number: 199 00390513666; Email: emanuela.palmerini@ior.it

Study Locations

• Italy
  • Bologna, Italy, 40136
    • Orthopedic Rizzoli Institute
  • Turin, Italy, 10126
    • Ospedale Infantile Regina Margherita
  • Mi
    • Milan, Mi, Italy, 20133
      • Fondazione IRCCS - Istituto Nazionale dei Tumori
  • Turin
    • Candiolo, Turin, Italy, 10060
      • Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia - IRCCS
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patient with advanced Ewing Sarcoma treated in clinic

Description

Inclusion Criteria:

1. Histological confirmed diagnosis of Ewing Sarcoma
2. Chemotherapic treatment with temozolomide and irinotecan
3. Written informed consent prior to any study related activities

Exclusion Criteria:

1. Lack of written informed consent for the study
2. Any situation that could interfere with the complete data collection of the clinical data related to the temozolomide and irinotecan treatment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Temozolomide and Irinotecan treatment; The group include all the patients with histological confirmed diagnosis of Ewing's Sarcoma who received chemotherapic treatment with temozolomide and irinotecan. In this group the MGMT methylation evaluation will be done	Other: MGMT methylation evaluation; The MGMT methylation will be evaluated by extracting DNA from fresh and Formalin Fixed paraffin Embedded (FFPE) tumor samples

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of MGMT promoter methylation	Amplification the methylation-specific Polymerase Chain Reaction products will be electrophoresed on a 2% agarose gel and will visualized with UV light	at day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of the MGMT promoter methylation to the activity of the temozolomide irinotecan combination	Correlation with level of MGMT methylation with tumor response	at month 2, 4, 6, 8, 10 and 12

Collaborators and Investigators

• Sponsor: Istituto Ortopedico Rizzoli
• Collaborators: Regione Emilia-Romagna
• Investigators: Principal Investigator: Emanuela Palmerini, MD, Rizzoli Orthopedic Institute

Publications and helpful links

General 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. doi: 10.1056/NEJMoa043331.
• Kushner BH, Meyers PA. How effective is dose-intensive/myeloablative therapy against Ewing's sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The Memorial Sloan-Kettering experience and a literature review. J Clin Oncol. 2001 Feb 1;19(3):870-80. doi: 10.1200/JCO.2001.19.3.870.
• Bacci G, Ferrari S, Longhi A, Donati D, De Paolis M, Forni C, Versari M, Setola E, Briccoli A, Barbieri E. Therapy and survival after recurrence of Ewing's tumors: the Rizzoli experience in 195 patients treated with adjuvant and neoadjuvant chemotherapy from 1979 to 1997. Ann Oncol. 2003 Nov;14(11):1654-9. doi: 10.1093/annonc/mdg457.
• Casey DA, Wexler LH, Merchant MS, Chou AJ, Merola PR, Price AP, Meyers PA. Irinotecan and temozolomide for Ewing sarcoma: the Memorial Sloan-Kettering experience. Pediatr Blood Cancer. 2009 Dec;53(6):1029-34. doi: 10.1002/pbc.22206.
• Donson AM, Addo-Yobo SO, Handler MH, Gore L, Foreman NK. MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma. Pediatr Blood Cancer. 2007 Apr;48(4):403-7. doi: 10.1002/pbc.20803.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2014
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: May 17, 2018
• First Submitted That Met QC Criteria: May 30, 2018
• First Posted (Actual): May 31, 2018

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Ewing Sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Sarcoma, Ewing
• Other Study ID Numbers: TEMIRI-EW

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No Plan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No