Genomic Landscape of EGFR Mutant NSCLC Prior to Erlotinib and at the Time of Disease Progression

Terminated

• Conditions: Nonsmall Cell Lung Cancer; Non-Small Cell Lung Cancer; Carcinoma, Non-Small-Cell-Lung

• Registration Number: NCT02431169
• Lead Sponsor: Washington University School of Medicine

Brief Summary

The investigators propose to conduct a pilot feasibility study of single agent erlotinib in patients with metastatic EGFR mutant adenocarcinoma of the lung with up to one prior treatment with the sole purpose of characterizing the genomic landscape before erlotinib and at the time of disease progression. The logistics of obtaining adequate quality fresh tissue specimens for sequencing studies before therapy and at the time of disease progression in patients with advanced lung cancer are complex and a thorough understanding of the practical challenges in conducting a study like this is crucial.

The current proposal will include exome and transcriptome sequencing from blood collected at baseline along with tumor samples obtained prior to starting erlotinib and at the time of disease progression (a total of two tissue samples and one blood sample per patient). If carried out successfully, the proposed strategy very likely will lead to a larger and adequately powered study to understand fully evolving molecular changes due to clonal selection under treatment pressure. The pace of progress in the field of sequencing technology currently underway is only likely to accelerate in the near future yielding richer and highly content-rich information. Moreover, it is likely that genomic information from DNA sequencing and transcriptome will be supplemented by analyses of translatomes and proteomes.

The investigators plan to sequence paired tumor specimens from 20 patients with EGFR mutant adenocarcinoma of the lung before treatment with erlotinib and at the time of disease progression following treatment with erlotinib. As the investigators expect some drop off (due to unexpected clinical events precluding a second biopsy at the time of disease progression, poor specimen quality and early discontinuation of therapy for non-progression), the investigators will enroll 40 patients in this trial to get 20-paired specimens.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-04-27
• Study First Submitted QC: 2015-04-27
• Study Start: 2015-04-30
• Study First Posted: 2015-04-30
• Primary Completion: 2019-06-27
• Study Completion: 2019-06-27
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-15
• Last Update Posted: 2019-07-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Genetic changes associated with disease progression following treatment with erlotinib in patients with activating mutations in the EGFR TK domain known to be responsive to therapy	Up to 3 years	Exome and transcriptome sequencing of tumor before therapy with erlotinib and at the time of relapse. In addition, exome sequencing of peripheral blood DNA will be done (for germ line).

Secondary Outcome Measures

Name	Time	Method
Correlate mutations in signaling kinases with therapeutic response	Up to 3 years
Correlate the allelic ratio of wild type to mutant EGFR with duration of response	Up to 3 years

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States