ESR1 Mutations in Asian ER+ Metastatic Breast Cancer on H... | NCT04212702

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

NCT04212702

Sponsor

National Taiwan University Hospital

Status

Unknown status

Last Update Posted

Jan 12, 2021Actual

Enrollment

123Actual

Phase

Not provided

Conditions

Metastatic Breast Cancer

Interventions

Hormonal therapy-based treatments

Countries

Taiwan

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Jan 2021

Overall Recruitment Status or Expanded Access Status

Unknown status

Last Known Status

Active, not recruiting

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

May 22, 2017Actual

Primary Completion Date

Feb 1, 2020Actual

Completion Date

Dec 31, 2021Estimated

First Submitted Date

Dec 25, 2019

First Submission Date that Met QC Criteria

Dec 25, 2019

First Posted Date

Dec 27, 2019Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Jan 11, 2021

Last Update Posted Date

Jan 12, 2021Actual

Name	Class
Novartis	INDUSTRY

Oversight Module

Has Data Monitoring Committee (DMC)

Not provided

Is FDA Regulated Drug

Is FDA Regulated Device

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

Brief 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.

Detailed 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.

Design Module

Study Type

Observational

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Target Follow-Up Duration

Not provided

Phases

Not provided

Interventional Study Design

Allocation

Not provided

Intervention Model

Biospecimen

Retention

Enrollment

123Actual

Arms/Interventions Module

Arm Groups

Not provided

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Hormonal therapy-based treatments	Drug	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		HT single agent, HT plus other targeted therapy, HT plus everolimus, HT plus metronomic oral chemotherapy or oral chemotherapy only

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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 Outcomes

Measure	Description	Time Frame
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

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

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.

Accepts Healthy Volunteers

Sex

Female

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

20 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Asian ER positive/HER2 negative metastatic breast cancer

Sampling Method

Probability Sample

Name	Affiliation	Role
Yen-Shen Lu, MD, PhD	National Taiwan University Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
National Taiwan University Hospital		Taipei		100	Taiwan
Tri-Service General Hospital

ID	Term
D001943	Breast Neoplasms

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases

ID	Term
D000068338	Everolimus

ID	Term
D020123	Sirolimus
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals

Description

Approximately 8 ml plasma sample will be prepared from 20 ml whole blood to be used for circulating cell free DNA (cfDNA) extraction using the QIAamp Circulating Nucleic Acid Kit (Qiagen, Hilden, Germany, Cat. No. 55114). DNA concentration will be determined by the Qubit fluorometer (Thermo Fisher Scientific, Wilmington, DE, USA) and DNA integrity will be analyzed using the capillary electrophoresis (AATI Fragment analyzer).