Epidermal Growth Factor Receptor (EGFR) T790M Mutation Testing Practices in Hong Kong

An Observational, Multi-centre Study on EGFR T790M Mutation Testing Practices and Outcomes Conducted Among Locally Advanced/Metastatic NSCLC Patients Who Progressed on Previous EGFR Tyrosine-kinase Inhibitor (TKI) Therapy in Hong Kong

To describe the T790M mutation status of patients with locally advanced/metastatic NSCLC who progressed on previous EGFR TKI treatment in a real-world setting.

Study Overview

• Status: Withdrawn
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Diagnostic test: Plasma-tissue testing

Detailed Description

This is a multi-center, observational study of patients with locally advanced/metastatic NSCLC who progressed on previous EGFR TKI treatment. Eligible patients will be recruited from participating sites in Hong Kong over a 12 months enrolment period.

Plasma and urine samples will be collected from enrolled patients. Plasma circulating tumor DNA (ctDNA) and urine ctDNA will be analyzed by droplet digital PCR (ddPCR) for detection of T790M mutation and EGFR sensitizing mutations. Patients who are T790M plasma-negative, regardless of the urine testing results, will be recommended to undergo re-biopsy (defined as tissue sampling or cytology sampling), tissue/cytology T790M testing, and to provide a second plasma sample for a second plasma T790M test (tested by ddPCR).

Enrolled patients who subsequently receive osimertinib treatment will be followed up as per routine practice at the investigational site. Patient data will be collected for 12 months or until death or loss to follow-up, whichever occurs earlier, from the first prescription of osimertinib. All clinical decisions will be at the discretion of the treating physician.

• Study Type: Observational

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study will enrol locally advanced or metastatic NSCLC patients with confirmed EGFR sensitizing mutation, who progressed after EGFR TKI treatment (i.e.,gefitinib, erlotinib, afatinib), and are suggested to undergo T790M mutation testing by their treating physicians in participating sites in Hong Kong

Description

Inclusion Criteria

• Provision of written informed consent
• Locally advanced (stage IIIB) or metastatic (stage IV) NSCLC, not amenable to curative surgery or radiotherapy
• Confirmed EGFR sensitizing mutation (exon 19 deletion or exon 21 L858R ) in medical record
• Progressed on previous EGFR TKI treatment, based on physician judgement, with or without additional lines of treatment
• Suggested to undergo T790M mutation testing by treating physician, based on physician judgement

Exclusion Criteria

• Had been treated with osimertinib or any other 3rd generation T790M inhibitors
• Enrollment in studies that prohibit participation in this observational study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
EGFR NSCLC Progressed on EGFR TKI; Patients with EGFR NSCLC who have progressed following EGFR TKI therapy will undergo plasma-tissue testing	Diagnostic test: Plasma-tissue testing; EGFR T790M mutation plasma-tissue testing in NSCLC patients who progressed on previous EGFR TKI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EGFR T790M mutation prevalance	Based on the plasma-tissue testing algorithm in NSCLC patients who progressed on previous EGFR TKI therapy	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Valid Tissue T790M Testing Result	Proportion of study subjects who have a valid tissue/cytology T790M testing result after receiving a negative plasma test result for the T790M mutation	3 years
T790M Plasma Outcome	Proportions of study subjects who are T790M plasma-negative	3 years
False Negative Proportation	Proportion of study subjects who are T790M plasma-negative but T790M tissue/cytology-positive	3 years
Reasons for not performing re-biopsy	reasons given for not performing re-biopsy and tissue/cytology testing after obtaining a negative plasma test result	3 years
Demographics	Demographics of T790M-positive subjects and T790M-negative subjects	Baseline
Disease Characteristics	Disease characteristics of T790M-positive subjects and T790M-negative subjects	3 years
Number of particapants with complications assoicated with re-biopsy	Number of particapants with complications assoicated with tissue/cytology re-biopsy	3 years
Clinical Outcomes in T790M plasma-positive subejects	Clinical outcomes after osimertinib treatment between study subjects who are T790M plasma-positive	3 years
Clinical Outcomes in urine-positive	Clinical outcomes after osimertinib treatment between study subjects who are urine-positive	3 years
Clinical Outcomes in tissue/cytology-positive	Clinical outcomes after osimertinib treatment between study subjects who are tissue/cytology-positive	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concordance	To analyze the concordance of T790M mutation status as determined by urine, plasma, and tissue/cytology T790M testing	3 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: James Ho, MBBS, Queen Mary Hospital, Hong Kong

Study record dates

Study Major Dates

• Study Start (Anticipated): September 30, 2018
• Primary Completion (Anticipated): November 30, 2020
• Study Completion (Anticipated): November 30, 2020

Study Registration Dates

• First Submitted: February 19, 2018
• First Submitted That Met QC Criteria: April 30, 2018
• First Posted (Actual): May 9, 2018

Study Record Updates

• Last Update Posted (Actual): November 16, 2018
• Last Update Submitted That Met QC Criteria: November 15, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: D5160R00019