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

Not Applicable

Recruiting

• Conditions: Breast Neoplasms; Neoplasms, Breast; Antineoplastic Agents; ESR1 Gene Mutation; Breast Diseases; Hormone Receptor Positive Breast Carcinoma; Aromatase Inhibitors
• Interventions: Diagnostic Test: Liquid biopsy and CT scan

• Registration Number: NCT05814224
• Lead Sponsor: Centro di Riferimento Oncologico - Aviano

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.

Study Timeline

• Study Start: 2018-05-22
• Status Verified: 2023-03
• Study First Submitted: 2023-03-24
• Study First Submitted QC: 2023-04-13
• Last Update Submitted: 2023-04-13
• Study First Posted: 2023-04-14
• Last Update Posted: 2023-04-14
• Primary Completion: 2023-12-31
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 164

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hormone-receptor positive MBC	Liquid biopsy and CT scan	Women with hormone receptor-positive MBC, that will be eligible for endocrine therapy as first line treatment

Primary Outcome Measures

Name	Time	Method
Liquid-biopsy in monitoring treatment response in luminal breast cancer	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

Secondary Outcome Measures

Name	Time	Method
Treatment resistance mechanisms	3 years	To investigate treatment resistance mechanisms and their detectability through ctDNA/miRNA analysis.
Time to Progression (TTP)	3 years	The time from first biomarker assessment until objective tumor progression.
ctDNA/miRNA based follow-up	3 years	To characterize the clinical implications of deploying a ctDNA/miRNA based follow-up both in terms of outcome and health systems management.
Negative predictive value	3 years	The proportion of patients correctly classified with a stable or response among those without clinico-radiological relapse.
Accuracy	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.
Overall Survival (OS)	3 years	The time from first biomarker assessment until death from any cause.
Overall Response Rate (ORR)	3 years	The sum of partial responses (PR) and complete responses (CR) evaluated from the time of first biomarker assessment to documented disease progression.
Positive predictive value	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).
Lead time (for PFS)	3 years	The time elapsed between the molecular detected progression and the imaging assessed one.
Number of futile diagnostic imaging	3 years	The number of imaging evaluations negative for progression and that could be avoided with the liquid biopsy technique.
Specificity	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.
Progression Free Survival (PFS)	3 years	The time from first biomarker assessment until objective tumor progression or death for any cause, whichever comes first.

Trial Locations

Locations (7)

Asst Papa Giovanni Xxiii- Bergamo; 🇮🇹 Bergame, Bergamo, Italy

Centro di Riferimento Oncologico - Aviano; 🇮🇹 Aviano, Pordenone, Italy

Asst Ospedali Civili Di Brescia; 🇮🇹 Brescia, Italy

Azienda Ospedaliero Universitaria Policlinico G. Rodolico- San Marco-Catania; 🇮🇹 Catania, Italy

Ospedale San Bortolo- Azienda Ulss8 Berica; 🇮🇹 Vicenza, Italy

Universita' Degli Studi Di Napoli Federico Ii; 🇮🇹 Napoli, Italy

azienda sanitaria universitaria friuli centrale- Udine; 🇮🇹 Udine, Italy