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

Active, not recruiting
Conditions
Biomarker
Interventions
Diagnostic Test: Validation of miRNA-serum signatures associated with IDH1 status
Registration Number
NCT06178692
Lead Sponsor
Regina Elena Cancer Institute
Brief Summary

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.

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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
30
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Arm 2Validation of miRNA-serum signatures associated with IDH1 statusIDH1 wt
Arm 1Validation of miRNA-serum signatures associated with IDH1 statusIDH1 mutated
Primary Outcome Measures
NameTimeMethod
Identification of specific forms of circulating microRNAs invasive brain tumorsEnlistment period: 6-12 months Total duration of the study: 18-24 months

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.

Secondary Outcome Measures
NameTimeMethod
Transfer of information in the clinical setting for diagnosisEnlistment period: 6-12 months Total duration of the study: 18-24 months

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.

Implementation of clinical trials leveraging know-how.Enlistment period: 6-12 months Total duration of the study: 18-24 months

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.

Trial Locations

Locations (1)

"Regina Elena" National Cancer Institute

🇮🇹

Rome, Italy

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