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NCT03191149 Clinical Trial

Osimertinib in Treating Patients With Stage IIIB-IV or Recurrent Non-small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations

Recurrent Lung Non-Small Cell Carcinoma Clinical Trial

Official title:
Phase II Study of Osimertinib (AZD9291) in Advanced NSCLC Patients With Exon 20 Insertion Mutations in EGFR

Clinical Trial Details — Status: Recruiting

Administrative data
NCT number NCT03191149
Other study ID # NCI-2017-01017
Secondary ID NCI-2017-01017EA
Status Recruiting
Phase Phase 2
First received
Last updated
Start date April 25, 2018
Est. completion date June 30, 2025

Study information
Verified date March 2024
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase II trial studies how well osimertinib works in treating patients with non-small cell lung cancer with EGFR exon 20 insertion mutation that is stage IIIB-IV or has come back (recurrent). Osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Description:

PRIMARY OBJECTIVE: I. To evaluate the best objective response rate of osimertinib (AZD9291) among patients with EGFR exon 20 insertions. SECONDARY OBJECTIVES: I. To determine the safety profile of 160 mg once daily (QD) dose of osimertinib (AZD9291) in patients with EGFR Exon 20 insertion mutations. II. To determine the progression-free survival. III. To determine the overall survival. TERTIARY OBJECTIVES: I. To characterize molecular markers of response to treatment in circulating tumor deoxyribonucleic acid (DNA). II. To evaluate biomarkers of response to treatment through retrospective analyses of pre-treatment tumor tissue. III. To identify resistance mechanisms to osimertinib (AZD9291) through post-progression tumor biopsies and circulating tumor (ct)DNA. OUTLINE: Patients receive osimertinib orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI) or computed tomography (CT) with contrast and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up at 30 days and every 3 months for up to 5 years.

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Study Design

Related Conditions & MeSH terms

  • Advanced Lung Non-Small Cell Carcinoma
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Recurrent Lung Non-Small Cell Carcinoma
  • Stage IIIB Lung Non-Small Cell Cancer AJCC v7
  • Stage IV Lung Non-Small Cell Cancer AJCC v7

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood samples
• Computed Tomography with Contrast
Undergo CT with contrast
• Magnetic Resonance Imaging
Undergo MRI
Drug:
• Osimertinib
Given PO
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Sponsors (1)
Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome
Type Measure Description Time frame Safety issue
Other Characterization of molecular markers of response to treatment in circulating tumor deoxyribonucleic acid (ctDNA) Initial analyses of data will utilize tests for association comparing the frequency of a particular genomic aberration at baseline and at progression (for example, using McNemar's test) and association between alterations and baseline characteristics (for example, using Fisher's exact test). More sophisticated analyses may include multivariable logistic regression modeling and/or competing risks analysis, however it is expected that analyzable results will not be obtained from 100% of patients (either due to things like assay failure, inability to biopsy at progression due to poor patient health, etc). Baseline up to 5 years
Other Biomarkers of response to treatment through retrospective analyses of pre-treatment tumor tissue The rate of change in allelic fraction at a particular time point may be compared to baseline measures of ctDNA and that measure will be analyzed for association with patient demographics and/or disease characteristics using the Kruskal Wallis test. Landmark analyses of PFS and OS in which the landmark time is defined by the ctDNA measurements at a particular time point, may be used as well. Baseline up to 5 years
Other Identification of resistance mechanisms to osimertinib through post-progression tumor biopsies and ctDNA Presence or absence of mutations in plasma will be analyzed for association with other variables using Fisher's exact test. To account for the repeated measures of plasma over time, we may potentially use these data as time varying covariates in multivariable Cox models to study their impact on outcomes like PFS and OS. Up to 5 years
Primary Best objective response Will be evaluated via Response Evaluation Criteria in Solid Tumors 1.1 criteria. Categorical data, such as response rates (complete response + partial response), will be compared using Fisher's exact tests with a one-sided type I error rate of 10%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes. Any continuous outcomes will be analyzed using Wilcoxon rank sum test, and multivariable linear regression models may be used to adjust for multiple associations with outcome. Point estimates of all endpoints will be accompanied by the corresponding two-sided 80% confidence intervals. The method of Atkinson and Brown will be used for the estimation of the confidence interval for response. Up to 5 years
Secondary Progression-free survival (PFS) Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate hazard ratios. Comparisons of groups will be made using the logrank test and Cox modeling. Point estimates of all endpoints will be accompanied by the corresponding two-sided 80% confidence intervals. The method of Atkinson and Brown will be used for the estimation of the confidence interval for response. From registration to documented disease progression or death from any cause, whichever occurs first, assessed up to 5 years
Secondary Overall survival (OS) Will be estimated using the Kaplan-Meier method, and Cox proportional hazards models will be used to estimate hazard ratios. Comparisons of groups will be made using the logrank test and Cox modeling. Point estimates of all endpoints will be accompanied by the corresponding two-sided 80% confidence intervals. The method of Atkinson and Brown will be used for the estimation of the confidence interval for response. From registration to death from any cause, assessed up to 5 years
Secondary Incidence of adverse events Will be graded according to Common Terminology Criteria for Adverse Events version 5.0. Categorical data, such as toxicity, will be compared using Fisher's exact tests with a one-sided type I error rate of 10%; multivariable logistic regression modeling will be used to adjust for the effect of any covariates that are associated with these categorical outcomes. Any continuous outcomes will be analyzed using Wilcoxon rank sum test, and multivariable linear regression models may be used to adjust for multiple associations with outcome. Point estimates of all endpoints will be accompanied by the corresponding two-sided 80% confidence intervals. The method of Atkinson and Brown will be used for the estimation of the confidence interval for response. Up to 5 years
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