Minimally Interventional Study on Prevalence of Emerging ESR1 Mutations in Liquid Biopsy in Three Cohorts of Patients With Breast Cancer in Comparison With Patient's Baseline ESR1 Mutation Status as Defined by Tissue Profiling.

NCT06417801 | Recruiting

• 1 other identifier: D3612L00003
• Study Type: observational
• Target: 170
• Locations: 1 country
• Sites: 6

Brief Summary

Minimally interventional study on prevalence of emerging ESR1 mutations in liquid biopsy in three cohorts of patients with breast cancer (with and without prior therapies in metastatic setting, and during first-line aromatase inhibitor plus CDK4/6 inhibitor therapy) in comparison with patient's baseline ESR1 mutation status as defined by tissue profiling.

Conditions

Metastatic Breast Cancer

Keywords

Breast Cancer; ER-positive; ESR-1 mutation

Outcome Measures

Primary Outcomes (1)

• Prevalence of emerging ESR1 mutations

  Primary objective A (Cohorts 1 and 2): to determine the prevalence of emerging ESR1 mutations in liquid biopsy samples from two cohorts of breast cancer patients (with and without prior treatment in the metastatic setting) and to compare this with the baseline ESR1 mutation status as determined by the patient's tissue profile. Primary objective B (Cohort 3): to determine the overall prevalence of emerging ESR1 mutations during first-line treatment with AI plus CDK4/6i in patients without clinical or radiological evidence of progressive disease, using a highly sensitive ctDNA assay.

  Through study completation, an avarege 2 years

Secondary Outcomes (1)

• Define the prevalence of PIK3CA, AKT1, PTEN, BRCA1, BRCA2, PALB2, ERBB2 mutations.

  Through study completation, an avarege 2 years

Study Arms (3)

Cohort 1 (N=30)

Locally-advanced/metastatic HR+/HER2- breast cancer, either treatment naive or previously exposed to adjuvant therapies, no prior palliative therapy, candidates to receive first-line hormone therapy, primary tumor tissue available.

Cohot 2 (N=40)

Locally-advanced/metastatic HR+/HER2- breast cancer, progression during hormone therapy plus CDK inhibitor; primary tumor tissue available.

Cohort 3 (N=100)

Locally advanced/metastatic HR+/HER2- breast cancer, with no disease progression during 6 months of hormonal therapy plus a CDK4/6 inhibitor; with archived tumour tissue available. Patients will be enrolled from the start of therapy with AI plus CDK4/6i in the metastatic setting (index date) up to 6 months into this first-line therapy, provided they have no clinical or radiological evidence of progressive disease. Patients will be followed up until disease progression.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

3 parallel cohorts: 1. Locally advanced/metastatic HR-positive/HER2-negative breast cancer, either treatment-naïve or having previously received adjuvant therapy, without prior palliative therapy, eligible for first-line hormonal therapy, with primary tumour tissue available; 2. Locally advanced/metastatic HR+/HER2- breast cancer, progression during treatment with hormone therapy plus a CDK inhibitor; with primary tumour tissue available; 3. Locally advanced/metastatic HR+/HER2- breast cancer, with no disease progression during 6 months of hormonal therapy plus a CDK4/6 inhibitor; with archived tumour tissue available. Patients will be enrolled from the start of therapy with AI plus CDK4/6i in the metastatic setting (index date) up to 6 months into this first-line therapy, provided they have no clinical or radiological evidence of progressive disease. Patients will be followed up until disease progression.

You may qualify if:

• Cohort 1:
• BC patients, male and female,
• years old and older,
• Pre or post menopausal,
• With HR+ (ER and/or PR positive) and Her-2 negative (confirmed centrally),
• Locally advanced irresectable and/or metastatic disease
• Confirmation of HR and Her-2 status may be performed in the primary tumor or in the metastatic lesion (patients with discordant results may be included),
• Patients must be candidates to CDK4/6i therapy in combination with endocrine therapy in the first line setting (with or without ovarian suppression)
• Patients may have received one previous line of chemotherapy in the metastatic setting, but no endocrine therapy in the metastatic setting is allowed,
• Patients may have received chemotherapy in the neo/adjuvant setting,
• Patients may have received endocrine therapy (with or without ovarian suppression) in the neo/adjuvant setting,
• Patients may have received a CDK4/6i in the adjuvant setting, provided they are still candidates for CDK4/6i therapy in the metastatic setting,
• Patients must be able to undergo a liquid biopsy procedure before starting their first line treatment,
• All patients must fill and sign an informed consent form.
• Cohort 2:

You may not qualify if:

• Patients WITHOUT HR+ (ER- and/or PR-positive)/HER2-negative disease,
• Patients without radiological and/or pathological confirmation of locally unresectable and/or metastatic breast cancer,
• Patients who are NOT candidates for further systemic treatment following a diagnosis of metastatic disease or disease progression,
• Patients who have already started a CDK4/6 inhibitor in combination with endocrine therapy (with or without ovarian suppression) for first-line metastatic disease (for Cohort 1);
• Patients who have already started a new line of treatment for metastatic disease following progression on a CDK4/6 inhibitor in combination with endocrine therapy (with or without ovarian suppression) (for Cohort 2);
• Patients with any suspicion of clinical or radiological disease progression at the time of the first liquid biopsy collection (for Cohort 3),
• Patients who are NOT able to undergo a liquid biopsy procedure,
• Patients who are NOT able to provide informed consent.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (6)

Ensino E Terapia de Inovação Clínica Amo - Ética

Salvador, Estado de Bahia, 41.950-640, Brazil

NOT YET RECRUITING

Irmandade Da Santa Casa de Misericórdia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

NOT YET RECRUITING

Fundação Antonio Prudente - A.C. Camargo Cancer Center

São Paulo, 01.509-900, Brazil

NOT YET RECRUITING

Instituto D'Or de Pesquisa E Ensino - São Paulo

São Paulo, 01401-002, Brazil

NOT YET RECRUITING

Research Site

São Paulo, 04513-020, Brazil

RECRUITING

Sociedade Beneficente Israelita Brasileira Hospital Albert Eisntein

São Paulo, 05652-000, Brazil

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Tissue.

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Rodrigo Dienstmann

  Oncoclínicas

  PRINCIPAL INVESTIGATOR

• Vladmir C. de Lima

  FUNDAÇÃO ANTONIO PRUDENTE - A.C. CAMARGO CANCER CENTER

  PRINCIPAL INVESTIGATOR

• Tomas Reinert

  IRMANDADE DA SANTA CASA DE MISERICÓRDIA DE PORTO ALEGRE

  PRINCIPAL INVESTIGATOR

• Renata Bonadio

  INSTITUTO D'OR DE PESQUISA E ENSINO - SÃO PAULO

  PRINCIPAL INVESTIGATOR

• Mayana Lopes

  ENSINO E TERAPIA DE INOVAÇÃO CLÍNICA AMO - ÉTICA

  PRINCIPAL INVESTIGATOR

• Leandro Jonata C. de Oliveira

  SOCIEDADE BENEFICENTE ISRAELITA BRASILEIRA HOSPITAL ALBERT EISNTEIN

  PRINCIPAL INVESTIGATOR

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2024
• First Posted: May 16, 2024
• Study Start: June 17, 2024
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

BR (6)