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

NCT02431169 | Terminated

• 1 other identifier: 201407158
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Carcinoma, Non-Small-Cell-Lung; Nonsmall Cell Lung Cancer

Outcome Measures

Primary Outcomes (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

  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).

  Up to 3 years

Secondary Outcomes (2)

• 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

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

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.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Daniel Morgensztern, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2015
• First Posted: April 30, 2015
• Study Start: April 30, 2015
• Primary Completion: June 27, 2019
• Study Completion: June 27, 2019
• Last Updated: July 18, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)