Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA (MAGNETIC1)

April 13, 2023 updated by: Centro di Riferimento Oncologico - Aviano
The purpose of the study is to determine the diagnostic role of ctDNA when used to monitor metastatic breast cancer (MBC) during first-line endocrine therapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients with hormone receptor-positive MBC are eligible for endocrine therapy (ET) as first line treatment which is based on strategies aimed to either block signaling pathways depending on the estrogen receptor (ESR1) or using ESR1 antagonists. Only a few accepted predictive factors are associated with treatment benefit for MBC (i.e., hormone receptor status and HER2 status). Furthermore, a standardized assessment evaluation for MBC is still lacking. Because of these unmet needs, ET is continued until disease progression, or if toxicity requiring discontinuation occurs. Resistance is frequent in the treatment of early BC and unavoidable in MBC. Recently, mutations in ESR1 have been described in MBC that had been previously exposed to aromatase inhibitors (AIs) and are rarely detectable in primary BC. Besides that, resistance phenomena have been also linked to ESR1 cisregulatory elements (CRE, i.e. enhancers and promoters) hypermethylation, both related to ESR1 silencing.

According to the literature, the aim of the study is to detect tumor response with liquid biopsy technique compared to conventional clinical pratice algorithms.

Study Type

Interventional

Enrollment (Anticipated)

164

Phase

  • Not Applicable

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

Study Contact Backup

Study Locations

  • Italy
      • Brescia, Italy
        • Recruiting
        • Asst Ospedali Civili Di Brescia
      • Catania, Italy
        • Recruiting
        • Azienda Ospedaliero Universitaria Policlinico G. Rodolico- San Marco-Catania
        • Contact:
          • PAOLO VIGNERI
      • Napoli, Italy
        • Recruiting
        • Universita' degli Studi di Napoli Federico II
        • Contact:
          • Mario Giuliano
      • Udine, Italy
        • Recruiting
        • azienda sanitaria universitaria friuli centrale- Udine
        • Contact:
      • Vicenza, Italy
        • Recruiting
        • Ospedale San Bortolo- Azienda Ulss8 Berica
        • Contact:
          • LAURA MERLINI
    • Bergamo
      • Bergame, Bergamo, Italy
        • Recruiting
        • Asst Papa Giovanni Xxiii- Bergamo
        • Contact:
          • CARLO ALBERTO TONDINI
    • Pordenone
      • Aviano, Pordenone, Italy, 33081
        • Recruiting
        • Centro di Riferimento Oncologico - Aviano
        • Contact:
        • 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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically proven diagnosis of adenocarcinoma of the breast with evidence of metastatic disease.
  • ER positive tumor ≥ 1%
  • HER2 negative breast cancer by FISH or IHC (IHC 0,1+, 2+ and/or FISH HER2: CEP17 ratio < 2.0)
  • Females, 18 years of age or older
  • Candidate to first-line endocrine therapy (LH-RH analogue for premenopausal women is allowed)
  • Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment.
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.

Exclusion Criteria:

  • Diagnosis of any secondary malignancy within the last 3 years, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
  • Prior endocrine therapy for metastatic disease

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Hormone-receptor positive MBC
Women with hormone receptor-positive MBC, that will be eligible for endocrine therapy as first line treatment
Diagnostic test: Liquid biopsy and CT scan

CT scan and liquid biopsy blood sample are performed at baseline, after 8 weeks from baseline and, then, every 12 weeks.

Between two subsequent CT scan another liquid biopsy blood sample is performed.

CEA and CA 15.3 will be performed at baseline and then concomitantly to the radiological evaluation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Liquid-biopsy in monitoring treatment response in luminal breast cancer
Time Frame: 3 years
The primary objective of this study is to evaluate whether liquid-biopsy technique is able to detect treatment response in luminal breast cancer through the quantification of ESR1 ctDNA mutations
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ctDNA/miRNA based follow-up
Time Frame: 3 years
To characterize the clinical implications of deploying a ctDNA/miRNA based follow-up both in terms of outcome and health systems management.
3 years
Treatment resistance mechanisms
Time Frame: 3 years
To investigate treatment resistance mechanisms and their detectability through ctDNA/miRNA analysis.
3 years
Specificity
Time Frame: From baseline until disease progression
The proportion of patients correctly classified with a stable or response disease through the genetic and epigenetic analysis of ESR1 ctDNA among those without clinicoradiological relapse.
From baseline until disease progression
Positive predictive value
Time Frame: 3 years
The proportion of patients correctly classified with a progressive disease through the genetic and epigenetic analysis of ESR1 ctDNA (i.e. those patients with molecular progression that is confirmed by clinic-radiological progression) among all patients with molecular progression (i.e. patients who show molecular progression irrespectively of clinic-radiological progression).
3 years
Negative predictive value
Time Frame: 3 years
The proportion of patients correctly classified with a stable or response among those without clinico-radiological relapse.
3 years
Accuracy
Time Frame: 6 months
Accuracy of the ESR1 ctDNA test in respect to correctly classify the patients with clinicoradiological relapse and without clinico-radiological relapse at 6 months.
6 months
Lead time (for PFS)
Time Frame: 3 years
The time elapsed between the molecular detected progression and the imaging assessed one.
3 years
Number of futile diagnostic imaging
Time Frame: 3 years
The number of imaging evaluations negative for progression and that could be avoided with the liquid biopsy technique.
3 years
Time to Progression (TTP)
Time Frame: 3 years
The time from first biomarker assessment until objective tumor progression.
3 years
Progression Free Survival (PFS)
Time Frame: 3 years
The time from first biomarker assessment until objective tumor progression or death for any cause, whichever comes first.
3 years
Overall Survival (OS)
Time Frame: 3 years
The time from first biomarker assessment until death from any cause.
3 years
Overall Response Rate (ORR)
Time Frame: 3 years
The sum of partial responses (PR) and complete responses (CR) evaluated from the time of first biomarker assessment to documented disease progression.
3 years

Collaborators and Investigators

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

Sponsor

Centro di Riferimento Oncologico - Aviano

Investigators

  • Principal Investigator: Fabio Puglisi, MD, Centro di Riferimento Oncologico - Aviano

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

May 22, 2018

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

March 24, 2023

First Submitted That Met QC Criteria

April 13, 2023

First Posted (Actual)

April 14, 2023

Study Record Updates

Last Update Posted (Actual)

April 14, 2023

Last Update Submitted That Met QC Criteria

April 13, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018.016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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