Clinical trial NCT03542097: Assessment of MGMT Promoter Methylation in Advanced Ewing Sarcoma Treated With Temozolomide and Irinotecan
Official title: Assessment of MGMT Promoter Methylation and Clinical Benefit From Temozolomide-based Therapy in Ewing Sarcoma Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ewing Sarcoma Family of Tumors
Keywords: Ewing Sarcoma
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
Collaborators: name: Regione Emilia-Romagna
First posted: 2018-05-31
Enrollment: 82
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patient with advanced Ewing Sarcoma treated in clinic

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

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.

Eligibility 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

Primary outcomes:
measure: Assessment of MGMT promoter methylation
timeFrame: at day 1
Secondary outcomes:
measure: Correlation of the MGMT promoter methylation to the activity of the temozolomide irinotecan combination
timeFrame: at month 2, 4, 6, 8, 10 and 12
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS - Istituto Nazionale dei Tumori
state: Mi
city: Candiolo
country: Italy
facility: Istituto di Candiolo - Fondazione del Piemonte per l'Oncologia - IRCCS
state: Turin
city: Bologna
country: Italy
facility: Orthopedic Rizzoli Institute
city: Turin
country: Italy
facility: Ospedale infantile Regina Margherita
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Rizzoli Orthopedic Institute
name: Emanuela Palmerini, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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.
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.
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.