Osimertinib for Russian EGFR T790M Mutation-positive NSCLC Patients Who Progressed on or After EGFR TKI Therapy (TRUST)

Multicenter Non-interventional Study of Osimertinib Administration in Patients With NSCLC Progression Occurred During or After Therapy With EGFR Tyrosine Kinase Inhibitors, With Confirmed Т790М Positive Mutation in EGFR Gene

The purpose of this study is to assess safety of Osimertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with progression during or after therapy with a prior EGFR tyrosine kinase inhibitor (TKI), with confirmed Т790М positive mutation in EGFR gene.

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer; EGFR Gene Mutation; T790M

Detailed Description

This study is a multicenter non-interventional retro- and prospective study of safety and efficacy of the Osimertinib administration in frames of Early Access Program (EAP) and real clinical practice in patients with locally advanced or metastatic non-small cell lung cancer that progressed during or after therapy with an EGFR tyrosine kinase inhibitor, with confirmed Т790М positive mutation in EGFR gene with explorative analysis of the set of mutations detected in plasma ctDNA taken after the progression on Osimertinib.

It is planned to include in the study approximately 70 patients in the Russian Federation (RF) who are participating or having completed their participation in EAP, or patients, who were treated with Osimertinib in real clinical practice.

For the patients participating in EAP and patients taking Osimertinib in real clinical practice, prospective data collection is planned after signing the informed consent form(ICF) for participation in the study. Data from those patients who completed participation in EAP or completed therapy with Osimertinib in real clinical practice will be gathered retrospectively, following the procedure of signing the ICF, or without it, if the procedure is not applicable (patient's death prior to the data collection).

Patients who are participating in EAP at the moment of inclusion into the TRUST study will receive therapy by Osimertinib at a dose of 80 mg a day orally, as a single dose. Patients will be treated according to the SmPC and local clinical regulations. Assessment of response to the therapy will be performed in accordance with RECIST 1.1.

From all patients included into the study will be performed retro- or prospective data collection of two-year-course of the disease starting from the time of first dose of Osimertinib.

For patients with progression of the disease on Osimertinib will be performed molecular-genetic testing of their plasma ctDNA at the time when the fact of the progression is registered.

During the study, each patient, for whom data will be collected prospectively, will undergo two data collection points: the first point (for signing of ICF and evaluation of eligibility criteria) and the final point, which will take place 2 years after the first dose of Osimertinib or at the time when therapy by Osimertinib is discontinued. Patients, for whom data will be collected retrospective, should underdo only the first visit for signing the ICF.

• Study Type: Observational
• Enrollment (Anticipated): 70

Contacts and Locations

• Study Contact: Name: Konstantin Laktionov, MD; Phone Number: +79031709795; Email: lkoskos@mail.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • Recruiting
    • Federal State Budgetary Institution National Medical Research Center of Oncology named after N.N. N.N. Blokhin" of the Ministry of Health of Russia
    • Contact: Konstantin Laktionov, M.D.; Phone Number: +79031709795; Email: lkoskos@mail.ru

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

The study plans to include all the patients enrolled in an Osimertinib Early Access Program in Russia With Locally Advanced/Metastatic EGFR T790M Mutation-positive NSCLC and Prior Exposure to and progression on or after other EGFR TKI Therapy (presumably 45 to 50 subjects) and patients, who were treated with osimertinib in local clinical practice (presumably 20 to 25 subjects).

Description

Inclusion Criteria:

• Participation in Osimertinib EAP and /or taking / completion therapy with Osimertinib in real clinical practice;
• Confirmed diagnosis of IIIB (locally advanced) or IV (metastatic) stages of NSCLC with T790M EGFRm;
• Progression of the disease that occurred during or after the therapy with first- or second-generation EGFR TKI

Exclusion Criteria:

• Participation in any other clinical study;
• Absence of data essential for obtaining all necessary information in full.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with at least one adverse event	By sex: Male; Female By line of treatment: First line therapy; Second line of therapy By treatment duration: Up to a year; More than a year By effectiveness of therapy: Progression; Stabilization; Negative feedback Previous targeted therapy: Yes; No Variant of mutation: Exon 19; Exon 21	Through study completion, an average of 5 years
Proportion of patients who discontinued therapy with Osimertinib	By sex: Male; Female By line of treatment: First line therapy; Second line of therapy By treatment duration: Up to a year; More than a year By effectiveness of therapy: Progression; Stabilization; Negative feedback Previous targeted therapy: Yes; No Variant of mutation: Exon 19; Exon 21	Through study completion, an average of 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate and Objective Response Rate	By sex: Male; Female Previous targeted therapy: Yes; No Variant of mutation: Exon 19; Exon 21	Through study completion, an average of 5 years
Progression-free survival	By sex: Male; Female Previous targeted therapy: Yes; No Variant of mutation: Exon 19; Exon 21	Through study completion, an average of 5 years
Overall Survival	By sex: Male; Female Previous targeted therapy: Yes; No Variant of mutation: Exon 19; Exon 21	Through study completion, an average of 5 years
Time to Treatment Discontinuation	By sex: Male; Female Previous targeted therapy: Yes; No Variant of mutation: Exon 19; Exon 21	Through study completion, an average of 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory outcome	Percentage of patients who had been treated with other therapies prior to the start of therapy with Osimertinib. Percentage of patients who previously underwent targeted therapy and other types of therapies.	Through study completion, an average of 5 years

Collaborators and Investigators

• Sponsor: N.N. Blokhin National Medical Research Center of Oncology

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: March 5, 2022
• First Submitted That Met QC Criteria: March 29, 2022
• First Posted (Actual): April 6, 2022

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: March 29, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Osimertinib; Tyrosine kinase inhibitor
• 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: ESR-17-13290

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No