Breast Cancer, Omics, and Precision Medicine (BR(E)2ASTOME)

August 7, 2021 updated by: Giuditta Benincasa, University of Campania "Luigi Vanvitelli"

Evaluating the Predictive and Prognostic Power of the Early Breast canceR gEnetic and Epigenetic Abnormalities Through Liquid biopSy and neTwOrk MEdicine Algorithm: the BR(E)2ASTOME Phase II Randomized Controlled Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • Inflammatory diseases
  • Cardiovascular diseases

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Biological: Next Generation Sequencing and Network Analysis
Next Generation Sequencing and Network Analysis will profile genetic and epigenetic abnormalities in blood from patients with BC.
No Intervention: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of Network-oriented buomarkers in prognosis of BC
Time Frame: 1 years

We will evaluate whether the network-oriented BR(E)2ASTOME approach will identify BC modules useful for a better stratification of BC severity.

We will measure:

DNA methylation levels and associations with clinical parameters (survival, hospitalization, all-cause mortality).

We will evaluate potential novel genetic mutations in targeted genes and associations with clinical parameters (survival, rate of hospitalization, all-cause mortality)
1 years
Evaluation of Network-oriented buomarkers of Drug Response
Time Frame: 2 years

We will evaluate whether the network-oriented BR(E)2ASTOME approach will identify BC modules useful for predicting the individual drug response.

We will measure DNA methylation levels, and potential novel genetic mutations, and their association with clinical parameters (poor/good response to drug therapy).
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Campania "Luigi Vanvitelli"

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2022

Primary Completion (Anticipated)

December 1, 2022

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

August 2, 2021

First Submitted That Met QC Criteria

August 2, 2021

First Posted (Actual)

August 9, 2021

Study Record Updates

Last Update Posted (Actual)

August 13, 2021

Last Update Submitted That Met QC Criteria

August 7, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LV

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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