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

Primary Purpose

Hormone Receptor Positive Breast Carcinoma, Breast Neoplasms, Neoplasms, Breast

Status
Recruiting
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Liquid biopsy and CT scan
Sponsored by
Centro di Riferimento Oncologico - Aviano
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Hormone Receptor Positive Breast Carcinoma focused on measuring Epigenetics, Liquid biopsy, ctDNA, ESR1 Gene Mutation, Biomarker, HR-positive HER2-negative, Advanced breast cancer, CDK4/6, Antineoplastic Agents Hormonal

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Asst Papa Giovanni Xxiii- BergamoRecruiting
  • Centro di Riferimento Oncologico - AvianoRecruiting
  • Asst Ospedali Civili Di BresciaRecruiting
  • Azienda Ospedaliero Universitaria Policlinico G. Rodolico- San Marco-CataniaRecruiting
  • Universita' Degli Studi Di Napoli Federico IiRecruiting
  • azienda sanitaria universitaria friuli centrale- UdineRecruiting
  • Ospedale San Bortolo- Azienda Ulss8 BericaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hormone-receptor positive MBC

Arm Description

Women with hormone receptor-positive MBC, that will be eligible for endocrine therapy as first line treatment

Outcomes

Primary Outcome Measures

Liquid-biopsy in monitoring treatment response in luminal breast cancer
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

Secondary Outcome Measures

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

Full Information

First Posted
March 24, 2023
Last Updated
April 13, 2023
Sponsor
Centro di Riferimento Oncologico - Aviano
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1. Study Identification

Unique Protocol Identification Number
NCT05814224
Brief Title
Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA
Acronym
MAGNETIC1
Official Title
Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 22, 2018 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centro di Riferimento Oncologico - Aviano

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hormone Receptor Positive Breast Carcinoma, Breast Neoplasms, Neoplasms, Breast, Breast Diseases, Antineoplastic Agents, Aromatase Inhibitors, ESR1 Gene Mutation
Keywords
Epigenetics, Liquid biopsy, ctDNA, ESR1 Gene Mutation, Biomarker, HR-positive HER2-negative, Advanced breast cancer, CDK4/6, Antineoplastic Agents Hormonal

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
164 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Hormone-receptor positive MBC
Arm Type
Experimental
Arm Description
Women with hormone receptor-positive MBC, that will be eligible for endocrine therapy as first line treatment
Intervention Type
Diagnostic Test
Intervention Name(s)
Liquid biopsy and CT scan
Intervention Description
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
Primary Outcome Measure Information:
Title
Liquid-biopsy in monitoring treatment response in luminal breast cancer
Description
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
Time Frame
3 years
Secondary Outcome Measure Information:
Title
ctDNA/miRNA based follow-up
Description
To characterize the clinical implications of deploying a ctDNA/miRNA based follow-up both in terms of outcome and health systems management.
Time Frame
3 years
Title
Treatment resistance mechanisms
Description
To investigate treatment resistance mechanisms and their detectability through ctDNA/miRNA analysis.
Time Frame
3 years
Title
Specificity
Description
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.
Time Frame
From baseline until disease progression
Title
Positive predictive value
Description
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).
Time Frame
3 years
Title
Negative predictive value
Description
The proportion of patients correctly classified with a stable or response among those without clinico-radiological relapse.
Time Frame
3 years
Title
Accuracy
Description
Accuracy of the ESR1 ctDNA test in respect to correctly classify the patients with clinicoradiological relapse and without clinico-radiological relapse at 6 months.
Time Frame
6 months
Title
Lead time (for PFS)
Description
The time elapsed between the molecular detected progression and the imaging assessed one.
Time Frame
3 years
Title
Number of futile diagnostic imaging
Description
The number of imaging evaluations negative for progression and that could be avoided with the liquid biopsy technique.
Time Frame
3 years
Title
Time to Progression (TTP)
Description
The time from first biomarker assessment until objective tumor progression.
Time Frame
3 years
Title
Progression Free Survival (PFS)
Description
The time from first biomarker assessment until objective tumor progression or death for any cause, whichever comes first.
Time Frame
3 years
Title
Overall Survival (OS)
Description
The time from first biomarker assessment until death from any cause.
Time Frame
3 years
Title
Overall Response Rate (ORR)
Description
The sum of partial responses (PR) and complete responses (CR) evaluated from the time of first biomarker assessment to documented disease progression.
Time Frame
3 years

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Females, 18 years of age or older
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fabio Puglisi, MD
Phone
0434 659310
Email
fabio.puglisi@cro.it
First Name & Middle Initial & Last Name or Official Title & Degree
Elisa De Crignis, PhD
Phone
0434-659077
Email
elisa.decrignis@cro.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fabio Puglisi, MD
Organizational Affiliation
Centro di Riferimento Oncologico - Aviano
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asst Papa Giovanni Xxiii- Bergamo
City
Bergame
State/Province
Bergamo
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
CARLO ALBERTO TONDINI
Facility Name
Centro di Riferimento Oncologico - Aviano
City
Aviano
State/Province
Pordenone
ZIP/Postal Code
33081
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabio Puglisi, MD
Phone
0434 659310
Email
fabio.puglisi@cro.it
First Name & Middle Initial & Last Name & Degree
Elisa De Crignis, PhD
Phone
0434 659077
Email
elisa.decrignis@cro.it
Facility Name
Asst Ospedali Civili Di Brescia
City
Brescia
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
VITO AMOROSO
Facility Name
Azienda Ospedaliero Universitaria Policlinico G. Rodolico- San Marco-Catania
City
Catania
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
PAOLO VIGNERI
Facility Name
Universita' Degli Studi Di Napoli Federico Ii
City
Napoli
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MARIO GIULIANO
Facility Name
azienda sanitaria universitaria friuli centrale- Udine
City
Udine
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
MARTA BONOTTO
Email
giada.carpi@cro.it
Facility Name
Ospedale San Bortolo- Azienda Ulss8 Berica
City
Vicenza
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
LAURA MERLINI

12. IPD Sharing Statement

Plan to Share IPD
Undecided
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Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA

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