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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04996836
Recruitment Status : Not yet recruiting
First Posted : August 9, 2021
Last Update Posted : August 13, 2021
Sponsor:
Information provided by (Responsible Party):
Giuditta Benincasa, University of Campania "Luigi Vanvitelli"

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: Next Generation Sequencing and Network Analysis Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single (Participant)
Primary Purpose: Other
Official Title: 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
Estimated Study Start Date : January 2022
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. 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)


  2. 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).




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Inflammatory diseases
  • Cardiovascular diseases

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04996836


Contacts
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Contact: Giuditta Benincasa, PhD +390815667916 giuditta.benincasa@unicampania.it

Sponsors and Collaborators
University of Campania "Luigi Vanvitelli"
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Responsible Party: Giuditta Benincasa, Principal Investigator, University of Campania "Luigi Vanvitelli"
ClinicalTrials.gov Identifier: NCT04996836    
Other Study ID Numbers: LV
First Posted: August 9, 2021    Key Record Dates
Last Update Posted: August 13, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Giuditta Benincasa, University of Campania "Luigi Vanvitelli":
Liquid biopsy
DNA methylation
Omics
Biomarkers
Network Analysis
Precision Medicine
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases