Impact of O6-methylguanine-DNA Methyltransferase (MGMT) Promoter Methylation and MGMT Expression on Dacarbazine Treated Sarcoma Patients (MGMT)

NCT04893356 | Unknown

• 1 other identifier: MGMT
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

MGMT study is a retrospective, non-profit, multi-center, observational study. The scientific objective of this study is to investigate whether MGMT expression or MGMT promoter methylation may represent a predictive marker for dacarbazine sensitivity in sarcoma patients.

Conditions

Sarcoma

Outcome Measures

Primary Outcomes (2)

• To analyze the expression of the MGMT gene in patients with Leiomyosarcoma (AML) and with metastatic Solitary Fibrous Tumor (SFT)

  1 year

• To analyze the methylation status of the MGMT promoter in histological specimens

  1 year

Secondary Outcomes (1)

• To investigate whether MGMT activity or MGMT promoter methylation may also represent a predictive marker for dacarbazine sensitivity in sarcomas

  1 year

Study Arms (1)

Dacarbazine treated sarcoma patients

Approximately 75 patients with histological diagnosis of Leiomyosarcoma (SCL) and Solitary Fibrous Tumor(SFT), previously treated with dacarbazine alone or associated with anthracyclines, will be enrolled, diagnosed from 2010 to 2020. From formalin fixed tumor samples, DNA will be extracted and MGMT expression and MGMT promoter methylation analyzed.

Genetic: O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and MGMT expression on dacarbazine treated sarcoma patients

Interventions

O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and MGMT expression on dacarbazine treated sarcoma patients GENETIC

Tumor samples of Leiomyosarcoma and Solitary Fibrous Tumours patients, dacarbazine (as single agents or in combination with anthracyclines) treated, will be obtained from and characterized by the Pathology Unit of the "Istituto Nazionale Tumori Fondazione Pascale" in Naples, Campus Biomedico of Rome, Istituto Oncologico of Bari and University of Palermo. Glioblastomas control samples will be obtained from CEINGE-Biotecnologie Avanzate, in Naples and characterized by the Pathology Unit of the University of Naples "Federico II". After biopsy or surgical resection, the tissues were fixed in 10% formalin and included in paraffin blocks. All patients partecipating in this study provided informed consent.

Dacarbazine treated sarcoma patients

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Tumor specimens from patients with Leiomyosarcoma (SCL) and Solitary Fibrous Tumors (SFT), treated with dacarbazine (as a single agent or in combination with anthracyclines), after biopsy or surgical resection, are fixed in 10% formalin and included in blocks of paraffin. They will be compared with control samples of glioblastomas (provided by the CEINGE-Biotechnologies Advanced, of Naples).

You may qualify if:

• \- Patients with a histological diagnosis of metastatic LMS and SFT from 2010 to 2020, previously treated with dacarbazine alone or with anthracyclines as first line of chemotherapy.

You may not qualify if:

• Patients with histological diagnosis of metastatic LMS and SFT, received before 2010.
• Patients with histological diagnosis of metastatic LMS and SFT from 2010 to 2020, never treated with dacarbazine
• Patients with a histological diagnosis of metastatic LMS and SFT from 2010 to 2020, previously treated with dacarbazine alone or with anthracyclines as the first line of chemotherapy, of which, however, there is no tissue sample

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (1)

National Cancer Institute of Naples

Naples, Campania, 80131, Italy

Location

Biospecimen

Retention: SAMPLES WITH DNA

Human DNA will be extracted from tumor tissues using the FFPE DNA Tissue Kit (Qiagen, Hilden, Germany), following the manufacturer's instructions. DNA quality will be checked using NanoDrop 2000 (Thermo Scientific, Waltham, MA, USA). Genomic DNA (500ng) will be converted by sodium bisulfite with the EZ DNA Methylation Gold Kit (Zymo Research, Irvine, CA, USA) and eluted in 20μL RNase free water, according to the manufacturer's instructions.

MeSH Terms

Conditions

Sarcoma

Interventions

O(6)-Methylguanine-DNA Methyltransferase

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Protein Methyltransferases; Methyltransferases; One-Carbon Group Transferases; Transferases; Enzymes; Enzymes and Coenzymes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: May 19, 2021
• Study Start: January 20, 2021
• Primary Completion: February 28, 2022
• Study Completion: January 20, 2025
• Last Updated: October 30, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)