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

Ewing Sarcoma Family of Tumors Clinical Trial

— MGMTLiberati  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03542097
• Other study ID #: TEMIRI-EW
• Status: Completed
• Start date: April 15, 2014
• Est. completion date: June 30, 2019

Study information

• Verified date: May 2023
• Source: Istituto Ortopedico Rizzoli
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: June 30, 2019
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Ewing Sarcoma Family of Tumors
• Sarcoma
• Sarcoma, Ewing

Intervention

Other:
• MGMT methylation evaluation
The MGMT methylation will be evaluated by extracting DNA from fresh and Formalin Fixed paraffin Embedded (FFPE) tumor samples

Locations

Country	Name	City	State
Italy	Orthopedic Rizzoli Institute	Bologna
Italy	Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia - IRCCS	Candiolo	Turin
Italy	Fondazione IRCCS - Istituto Nazionale dei Tumori	Milan	Mi
Italy	Ospedale infantile Regina Margherita	Turin
United Kingdom	The Royal Marsden NHS Foundation Trust	London

Sponsors (2)

Lead Sponsor	Collaborator
Istituto Ortopedico Rizzoli	Regione Emilia-Romagna

Countries where clinical trial is conducted

Italy,  United Kingdom, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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