ESR1 Mutations in Asian ER+ Metastatic Breast Cancer on Hormonal Therapy-based Treatments

Metastatic Breast Cancer Clinical Trial

Official title:

The Landscape of ESR1 Mutations in Asian Estrogen Receptor-positive Metastatic Breast Cancer Patients Detected by Liquid Biopsy and Impact on Hormonal Therapy-based Treatments

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04212702
• Other study ID #: 201703138RIPD
• Status: Active, not recruiting
• Start date: May 22, 2017
• Est. completion date: December 31, 2021

Study information

• Verified date: January 2021
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigator propose a prospective study using blood samples (liquid biopsy) of estrogen receptor (ER)-positive metastatic breast cancer (MBC) patients to understand the prevalence of estrogen receptor 1 (ESR1) mutation variants and the correlation with hormonal therapy (HT)-based treatment resistance in Asian ER-positive/human epidermal growth receptor-2 (HER2)-negative MBC population.

Description:

The investigator will use next-generation targeted sequencing covering the entire ESR1 ligand-binding domain (LBD) region to understand 1. the spectrum and prevalence of specific ESR1 mutation variants in Asian women, and 2. the preliminary correlation of Asian-specific prevalent ESR1 LBD mutation variants such as Y537C with treatment efficacy. For the second purpose, the investigator will specifically focus on patients with ESR1 Y537C mutation, while the results from patients with wild type ESR1 and patients with D538G or Y537S mutant will be severed as control for preliminary comparison.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 123
• Est. completion date: December 31, 2021
• Est. primary completion date: February 1, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• (1) Female patients who are = 20 years old at the time of informed consent.
• (2) Have histologically confirmed ER positive (defined as =1%) and/ or progesterone receptor (PR) positive (defined as =1%) breast cancer.
• (3) Have histologically confirmed HER2-negative breast cancer as defined by immuno-histochemistry (IHC) = 2+, and/or fluorescence in situ hybridization (FISH) negative.
• (4) Patients who fits either one of the following two criteria are eligible: I. Have radiological or objective evidence of inoperable locally advanced or metastatic breast cancer and are planned to be given HT single agent, HT plus other targeted therapy, HT plus everolimus (reimbursed by National Health Insurance), HT plus metronomic oral chemotherapy or oral chemotherapy only by the treating physician. II. Locally advanced but operable patients before the resection of the primary tumor.

Exclusion Criteria:

• (1) Patients not suitable for oral anti-cancer treatment as determined by the investigator.
• (2) Known hypersensitivity to mammilian target of rapamycin (mTOR) inhibitors, e.g. Sirolimus (rapamycin).
• (3) Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.
• (4) Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Hormonal therapy-based treatments
Hormonal therapy-based treatments, ex. HT single agent, HT plus other targeted therapy, HT plus everolimus, HT plus metronomic oral chemotherapy or oral chemotherapy only

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
National Taiwan University Hospital	Novartis

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The percentage of ESR1 LBD mutation variant	The percentage of each ESR1 LBD mutation variant in Asian ER-positive/HER2-negative MBC who had received at least one line of HT	12 months
Secondary	Progression-free Survival (PFS)	PFS of patients who are treated with everolimus plus HT with either ESR1 wild type or different Asian-specific prevalent ESR1 LBD mutation variants such as Y537C	12 months