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

• ClinicalTrials.gov Identifier: NCT03542097
• Recruitment Status: Unknown
• First Posted: May 31, 2018
• Last Update Posted: May 31, 2018
• Sponsor: Istituto Ortopedico Rizzoli
• Collaborator: Regione Emilia Romagna - Italy within PRU-Liberati project
• Information provided by (Responsible Party): Istituto Ortopedico Rizzoli

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment
Ewing Sarcoma Family of Tumors	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 Design

• Study Type: Observational
• Estimated Enrollment: 82 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Assessment of MGMT Promoter Methylation and Clinical Benefit From Temozolomide-based Therapy in Ewing Sarcoma Patients
• Actual Study Start Date: April 15, 2014
• Estimated Primary Completion Date: December 31, 2018
• Estimated Study Completion Date: June 30, 2019

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Correlation of the MGMT promoter methylation to the activity of the temozolomide irinotecan combination [ Time Frame: at month 2, 4, 6, 8, 10 and 12 ]
   Correlation with level of MGMT methylation with tumor response

Biospecimen Retention:   Samples With DNA

Fresh and Formaline Fixed Paraffin Embeded tumor samples

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Patient with advanced Ewing Sarcoma treated in clinic

Criteria

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

Contacts and Locations

Contacts

Contact: Emanuela Palmerini, MD; 00390513666 ext 199; emanuela.palmerini@ior.it

Locations

Italy

Fondazione IRCCS - Istituto Nazionale dei Tumori; Completed

Milan, Mi, Italy, 20133

Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia - IRCCS; Completed

Candiolo, Turin, Italy, 10060

Orthopedic Rizzoli Institute; Recruiting

Bologna, Italy, 40136

Contact: Emanuela Palmerini, MD 00390516366 ext 199 emanuela.palmerini@ior.it

Principal Investigator: Emanuela Palmerini, MD

Ospedale infantile Regina Margherita; Completed

Turin, Italy, 10126

United Kingdom

The Royal Marsden NHS Foundation Trust; Not yet recruiting

London, United Kingdom, SW3 6JJ

Contact: Robin Jones, MD 00442078082200 ext 2590 robin.jones4@nhs.net

Principal Investigator: Robin Jones, MD

Sponsors and Collaborators

Istituto Ortopedico Rizzoli

Regione Emilia Romagna - Italy within PRU-Liberati project

Investigators

• Principal Investigator: Emanuela Palmerini, MD; Rizzoli Orthopedic Institute

  Study Documents (Full-Text)

Documents provided by Istituto Ortopedico Rizzoli:

Study Protocol  [PDF] January 7, 2014

More Information

Publications:

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. Review.

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.

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.

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.

• Responsible Party: Istituto Ortopedico Rizzoli
• ClinicalTrials.gov Identifier: NCT03542097
• Other Study ID Numbers: TEMIRI-EW
• First Posted: May 31, 2018
• Last Update Posted: May 31, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No Plan

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Istituto Ortopedico Rizzoli:

Ewing Sarcoma

Additional relevant MeSH terms:

Sarcoma; Sarcoma, Ewing; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue