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

ID: NCT02431169
Status: Recruiting
Phase: N/A
Start Date: April 30, 2015
First Submitted: April 27, 2015
Last Updated: February 23, 2018
Results: N/A
Sponsors & Collaborators: Washington University School of Medicine
Location: United States
Conditions: Carcinoma, Non-Small-Cell-Lung, Non-Small Cell Lung Cancer, Nonsmall Cell Lung Cancer
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Study Description

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

Condition or disease Intervention/treatment Phase

Carcinoma, Non-Small-Cell-Lung

Non-Small Cell Lung Cancer

Nonsmall Cell Lung Cancer

N/A

Tracking Information

First Submitted DateApril 27, 2015
Last Update Posted DateFebruary 23, 2018
Actual Start DateApril 30, 2015
Anticipated Completion DateMay 31, 2018
Actual Primary Completion DateMay 31, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • 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 [Time Frame: 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).

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Correlate mutations in signaling kinases with therapeutic response [Time Frame: Up to 3 years]

  • Correlate the allelic ratio of wild type to mutant EGFR with duration of response [Time Frame: Up to 3 years]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleGenomic Landscape of EGFR Mutant NSCLC Prior to Erlotinib and at the Time of Disease Progression
Official TitleGenomic Landscape of EGFR Mutant NSCLC Prior to Erlotinib and at the Time of Disease Progression Following Erlotinib
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

Study TypeObservational
Study PhaseN/A
Estimated Enrollment
40
Allocation
Not Available
Interventional Model
Not Available
Masking
Not Available
Primary Purpose
Not Available
Conditions
Carcinoma, Non-Small-Cell-Lung
Non-Small Cell Lung Cancer
Nonsmall Cell Lung Cancer
Target Follow-Up Duration N/A
Biospecimen:
Retention: Samples With DNA
Description: - Specimen (tissue and blood) acquisition will take place under Washington University's study HRPO# 201305031 and will be analyzed under this study. - Fresh tissue will be taken at the time of diagnosis of metastatic disease and again at progression.
Sampling MethodNon-Probability Sample
Study PopulationStudy population will consist of participants with stage IIIB/IV non-small cell lung cancer with presence of known sensitizing mutations in the EGFR TK domain and absense of known resistant mutations in the EGFT TK domain.
Intervention
Not Available
Study Groups/Cohorts
Not Available
Study Arms
Not Available
Arm Intervention/Treatment

Recruitment Information

Recruitment Status:Recruiting
Enrollment40
Completion DateMay 31, 2018
Eligibility Criteria: Patient Selection
- Diagnosis of metastatic stage IIIB/IV lung adenocarcinoma
- Presence of known sensitizing mutations in EGFR TK domain
- Consented to HRPO# 201305031 ("Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information from Patients with Thoracic Malignancies, Suspected -Thoracic Malignancies, or Mesothelioma")
- Treatment with standard of care erlotinib
- At least 18 years of age
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
United States

Administrative Information

NCT Number:NCT02431169
Other Study ID Numbers
201407158
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Washington University School of Medicine
Collaborators
Not Available
Investigators
Principal Investigator
Daniel Morgensztern, M.D.
Washington University School of Medicine