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

• ClinicalTrials.gov Identifier: NCT02431169
• Recruitment Status: Terminated
• First Posted: April 30, 2015
• Last Update Posted: July 18, 2019
• Sponsor: Washington University School of Medicine
• Information provided by (Responsible Party): Washington University School of Medicine

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.

Condition or disease
Carcinoma, Non-Small-Cell-Lung; Non-Small Cell Lung Cancer; Nonsmall Cell Lung Cancer

Study Design

• Study Type: Observational
• Actual Enrollment: 5 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Genomic Landscape of EGFR Mutant NSCLC Prior to Erlotinib and at the Time of Disease Progression Following Erlotinib
• Actual Study Start Date: April 30, 2015
• Actual Primary Completion Date: June 27, 2019
• Actual Study Completion Date: June 27, 2019

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. 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).

Secondary Outcome Measures :

1. Correlate mutations in signaling kinases with therapeutic response [ Time Frame: Up to 3 years ]
2. Correlate the allelic ratio of wild type to mutant EGFR with duration of response [ Time Frame: Up to 3 years ]

Biospecimen Retention:   Samples With DNA

• 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Study 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.

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

Contacts and Locations

Locations

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

Investigators

• Principal Investigator: Daniel Morgensztern, M.D.; Washington University School of Medicine

More Information

Additional Information:

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine 

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT02431169
• Other Study ID Numbers: 201407158
• First Posted: April 30, 2015
• Last Update Posted: July 18, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Disease Progression; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Disease Attributes; Pathologic Processes