Validation Study of a Serum-miRNA Signature in Glioma Patients.

Validation Study of a Serum-miRNA Signature, Associated With IDH1 Stuatus, as Non-invasive Diagnostic and Prognostic Biomarkers in Glioma Patients

Prospective, multicenter, noninterventional, nonprofit study of a cohort of patients with glioma, aimed at validating miRNA-serum signatures associated with IDH1 status and prognosis, as reliable, specific and sensitive circulating diagnostic biomarkers also useful for improve prognostic stratification of patients. The study will be conducted on serum samples at diagnosis, at 4-6 days postoperatively and/or at the first post-surgery follow-up, in a new cohort of glioma patients and representative of different IDH1 mutational statuses. Furthermore, because comparison of miRNA expression profiles in serum and tissue may provide further evidence to support the use of serum miRNAs as reliable biomarkers reliable, their expression will also be analyzed, where possible, in tissue biopsies from the same patient and compared with the expression profiles of serum miRNAs.

Study Overview

• Status: Active, not recruiting
• Conditions: Biomarker
• Intervention / Treatment: Diagnostic test: Validation of miRNA-serum signatures associated with IDH1 status

Detailed Description

Scientific data suggest that a serum signature of miRNA could be a promising noninvasive diagnostic and prognostic tool for stratify, by liquid biopsy, patients with glioma according to IDH1 status. It has the primary objective of validating, through non-invasive methods, a signature of Serum miRNAs as reliable, specific and sensitive diagnostic and/or prognostic biomarkers for patients affected by glioma which can also help integrate the molecular analyzes performed on biopsies tissue. The ultimate goal is therefore to validate specific biomarkers for a "medicine" approach personalized" for glioma patients, with potential clinical benefits resulting from improved patient management and identification of the best possible therapy for specific subgroups biological data of patients. Blood samples from cancer patients will be used brain with different IDH1 status and of different grade, recruited from the centers participating in the study.

Where possible, tissue samples coming, according to clinical practice, from biopsy will be used to the diagnosis of the same patient.

For the analyzes foreseen by the study it will be necessary to take two test tubes (6ml each) with activator of peripheral blood coagulation at diagnosis, at discharge after surgery (4-6 days after surgery) and/or at the first post-surgery check-up. From the serum obtained from blood samples will subsequently be extracted the RNA and the expression level of the miRNAs will be analyzed in individual samples by digital PCR.

The method of collection of peripheral blood samples at diagnosis, discharge and/or following the first post-surgery check-up it will be kept uniform throughout study, to minimize preanalytical variables. Any hemolyzed samples will be identified, and excluded from the study, through spectrophotometric analysis and/or by analyzing the level of expression of miR-451, abundant in erythrocytes, and miR-23a, not affected by hemolysis.

Where possible, biopsy tissue taken for diagnostic purposes and fixed in formalin and embedded in paraffin (FFPE) will be analyzed for the expression of miRNAs of interest by Real-Time PCR.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00144
    • "Regina Elena" National Cancer Institute

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Prospective, multicenter, noninterventional, nonprofit study of a cohort of patients with glioma, aimed at validating miRNA-serum signatures associated with IDH1 status and prognosis, as reliable, specific and sensitive circulating diagnostic biomarkers also useful for improve prognostic stratification of patients.

The study will be conducted on serum samples at diagnosis, at 4-6 days postoperatively and/or at the first post-surgery follow-up, in a new cohort of glioma patients and representative of different IDH1 mutational statuses.

Description

Inclusion Criteria:

• histological diagnosis of glioma;
• age≥18 years;
• No other primary tumor;
• No metastatic disease
• Informed consent on treatment and molecular analysis

Exclusion Criteria:

• Histological diagnosis of non-glial tumor;
• age< 18;
• patients with concomitant other solid tumors
• metastatic disease; HIV seropositivity.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm 1; IDH1 mutated	Diagnostic test: Validation of miRNA-serum signatures associated with IDH1 status; Validation of miRNA-serum signatures associated with IDH1 status and prognosis, as reliable, specific and sensitive circulating diagnostic biomarkers also useful to improve prognostic stratification of patients.
Arm 2; IDH1 wt	Diagnostic test: Validation of miRNA-serum signatures associated with IDH1 status; Validation of miRNA-serum signatures associated with IDH1 status and prognosis, as reliable, specific and sensitive circulating diagnostic biomarkers also useful to improve prognostic stratification of patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of specific forms of circulating microRNAs invasive brain tumors	Identification of specific circulating microRNA signatures as non-diagnostic biomarkers invasive brain tumors. The variables of interest will be summarized by descriptive statistics. ROC curve analysis will be used to evaluate the diagnostic accuracy of miRNAs to be validated. Survival analysis (Overall Survival=OS and Progression Free Survival=PFS) will be conducted through the use of the Kaplan-Meier model and risk regression models Cox proportionals. The log-rank test will be used to test for any differences between groups. The Hazard Risk (HR) and related 95% confidence intervals (95%CI) will be estimated for each variable using univariate and multivariate Cox models. A p value <0.05 will be considered statistically significant. All analyzes will be conducted with SPSS v.21.0 software.	Enlistment period: 6-12 months Total duration of the study: 18-24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transfer of information in the clinical setting for diagnosis	Transfer of this information into the clinical setting for diagnosis, prognosis and purposes therapeutic. The variables of interest will be summarized by descriptive statistics. ROC curve analysis will be used to evaluate the diagnostic accuracy of miRNAs to be validated. Survival analysis (Overall Survival=OS and Progression Free Survival=PFS) will be conducted through the use of the Kaplan-Meier model and risk regression models Cox proportionals. The log-rank test will be used to test for any differences between groups. The Hazard Risk (HR) and related 95% confidence intervals (95%CI) will be estimated for each variable using univariate and multivariate Cox models. A p value <0.05 will be considered statistically significant. All analyzes will be conducted with SPSS v.21.0 software.	Enlistment period: 6-12 months Total duration of the study: 18-24 months
Implementation of clinical trials leveraging know-how.	Implementation and interpretation of clinical trials using specific know-how generated by the collaborative effort of study participants. The variables of interest will be summarized by descriptive statistics. ROC curve analysis will be used to evaluate the diagnostic accuracy of miRNAs to be validated. Survival analysis (Overall Survival=OS and Progression Free Survival=PFS) will be conducted through the use of the Kaplan-Meier model and risk regression models Cox proportionals. The log-rank test will be used to test for any differences between groups. The Hazard Risk (HR) and related 95% confidence intervals (95%CI) will be estimated for each variable using univariate and multivariate Cox models. A p value <0.05 will be considered statistically significant. All analyzes will be conducted with SPSS v.21.0 software.	Enlistment period: 6-12 months Total duration of the study: 18-24 months

Collaborators and Investigators

• Sponsor: Regina Elena Cancer Institute
• Collaborators: University of Roma La Sapienza; Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta; Azienda Ospedaliero Universitaria di Sassari; Plymouth State University
• Investigators: Principal Investigator: Maria Giulia Rizzo, Doctor, IRCCS "Regina Elena" National Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2020
• Primary Completion (Actual): November 17, 2022
• Study Completion (Estimated): May 10, 2024

Study Registration Dates

• First Submitted: March 28, 2023
• First Submitted That Met QC Criteria: December 18, 2023
• First Posted (Estimated): December 21, 2023

Study Record Updates

• Last Update Posted (Estimated): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: RS1337/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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