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

• ClinicalTrials.gov Identifier: NCT04996836
• Recruitment Status: Unknown
• First Posted: August 9, 2021
• Last Update Posted: August 13, 2021
• Sponsor: University of Campania "Luigi Vanvitelli"
• Information provided by (Responsible Party): Giuditta Benincasa, University of Campania "Luigi Vanvitelli"

Tracking Information

• First Submitted Date: August 2, 2021
• First Posted Date: August 9, 2021
• Last Update Posted Date: August 13, 2021
• Estimated Study Start Date: January 2022
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 7, 2021)

• 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)
• 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).

Original Primary Outcome Measures (submitted: August 2, 2021)

• Prognosis [ 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.
• Prediction 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.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Breast Cancer, Omics, and Precision Medicine
• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Single (Participant); Primary Purpose: Other
• Condition: Breast Cancer

Intervention

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.

Study Arms

• 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
  Intervention: Biological: Next Generation Sequencing and Network Analysis
• 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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 2, 2021): 200
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

• Inflammatory diseases
• Cardiovascular diseases

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04996836
• Other Study ID Numbers: LV
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Giuditta Benincasa, University of Campania "Luigi Vanvitelli"
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Campania "Luigi Vanvitelli"
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University of Campania "Luigi Vanvitelli"
• Verification Date: August 2021