Clinical trial NCT05814224: Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA
Official title: Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: 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
Lead sponsor: Centro di Riferimento Oncologico - Aviano
Sponsor class: OTHER
First posted: 2023-04-14
Enrollment: 164
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Liquid-biopsy in monitoring treatment response in luminal breast cancer
timeFrame: 3 years
Secondary outcomes:
measure: ctDNA/miRNA based follow-up
timeFrame: 3 years
measure: Treatment resistance mechanisms
timeFrame: 3 years
measure: Specificity
timeFrame: From baseline until disease progression
measure: Positive predictive value
timeFrame: 3 years
measure: Negative predictive value
timeFrame: 3 years
measure: Accuracy
timeFrame: 6 months
measure: Lead time (for PFS)
timeFrame: 3 years
measure: Number of futile diagnostic imaging
timeFrame: 3 years
measure: Time to Progression (TTP)
timeFrame: 3 years
measure: Progression Free Survival (PFS)
timeFrame: 3 years
measure: Overall Survival (OS)
timeFrame: 3 years
measure: Overall Response Rate (ORR)
timeFrame: 3 years
Other outcomes:
Locations:
city: Bergame
country: Italy
facility: Asst Papa Giovanni Xxiii- Bergamo
state: Bergamo
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - Aviano
state: Pordenone
city: Brescia
country: Italy
facility: Asst Ospedali Civili Di Brescia
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico G. Rodolico- San Marco-Catania
city: Napoli
country: Italy
facility: Universita' Degli Studi Di Napoli Federico Ii
city: Udine
country: Italy
facility: azienda sanitaria universitaria friuli centrale- Udine
city: Vicenza
country: Italy
facility: Ospedale San Bortolo- Azienda Ulss8 Berica
Study officials:
affiliation: Centro di Riferimento Oncologico - Aviano
name: Fabio Puglisi, MD
role: PRINCIPAL_INVESTIGATOR
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