Breast Cancer, Omics, and Precision Medicine

NCT ID: NCT04996836

Last Updated: 2021-08-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-31
• Study Completion Date: 2023-12-31

Brief Summary

The standard tissue biopsy strategy for cancer detection is not comprehensive enough to profile the whole epi-genomic signatures of breast cancer (BC) and ensure an accurate prognosis and prediction of drug response. Liquid-based assays have the potential to reduce the molecular heterogeneity of BC and a possible utility for improving disease management. In particular, genomic DNA (gDNA) and circulating tumor (ctDNA) can be sequenced for genetic and epigenetic (DNA methylation) profiling of the BC patients to enhance personalized prognosis and prediction of drug therapy. We describe a study protocol for evaluating the clinical utility of the early use of the network-oriented BR(E)2ASTOME algorithm which combine the power of liquid-based assays, advanced epi-genomics platform, and network analysis to identify improve precision medicine and personalized therapy of BC.

Detailed Description

The BR(E)2ASTOME study will be performed at the U.O.C. Patologia Molecolare e Clinica, University of Campania "L. Vanvitelli", Naples (Italy) with a long-standing experience in diagnosis and treatment of BC (Refs.). From each study participant, total of 10 mL of pheripheral blood in EDTA tubes will be collected at time of BC diagnosis. Blood-based assays will be performed to obtain genetic and/or epigenetic big data from ct-DNA and gDNA, respectively. A network-oriented algorithm combined with patient-level clinical information will be applied to big data in order to identify clusters of genes (BC-modules) harboring novel genetic mutations, in the NGS-ctDNA BC-group, and differentially methylated regions (DMRs), in the RRBS-gDNA group, with a potential predictive and prognostic role in BC management. In the NGS-ctDNA-RRBS-gDNA group, we will evaluate whether the multi-omics approach is more informative as compared to the single-omic paradigm.

BC patients (males and females) will be randomized to the 2 study arms: ctDNA-NGS + gDNA-RRBS, and standard of care alone. No modifications of intervention assignment will be possible after randomization process of patients. The BR(E)2ASTOME study will provide evidence about the potential clinical utility of early use liquid-based assays and network-oriented biomarkers in prognosis and prediction of drug response in BC management.

Thus, results from BR(E)2ASTOME study will bring to identify not only new molecular mechanisms associated with BC, but also non-invasive biomarkers that can direct towards an early diagnosis, contribute to monitor the cancer progression and the response to therapeutic treatment.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

BC diagnosis and Omics

Participants will be offered:

1. Liquid biopsy of ctDNA and targeted NGS (BRCA1, BRCA2, CHEK2, PALB2, BRIP1, TP53, PTEN, STK11, CDH1, ATM, BARD1, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PMS1, PMS2, RAD50, RAD51C, RAD51D, NF1, EPCAM, SMARCA4, CDK12);

2. Whole-genome RRBS

Group Type: EXPERIMENTAL

Next Generation Sequencing and Network Analysis

Intervention Type: BIOLOGICAL

Next Generation Sequencing and Network Analysis will profile genetic and epigenetic abnormalities in blood from patients with BC.

BC diagnosis and standard of the care

Participants will not be offered targeted NGS or whole-genome RRBS but will receive their usual clinical care

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Next Generation Sequencing and Network Analysis

Next Generation Sequencing and Network Analysis will profile genetic and epigenetic abnormalities in blood from patients with BC.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Sporadic BC
• Inherited BC
• 18 years old
• Males and Females

Exclusion Criteria

• Inflammatory diseases
• Cardiovascular diseases

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Campania Luigi Vanvitelli

OTHER

Sponsor Role: lead

Responsible Party

Giuditta Benincasa

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Giuditta Benincasa, PhD

Role: CONTACT

giuditta.benincasa@unicampania.it

+390815667916

Other Identifiers

LV

Identifier Type: -

Identifier Source: org_study_id