Clinical trial NCT02431169: Genomic Landscape of EGFR Mutant NSCLC Prior to Erlotinib and at the Time of Disease Progression
Official title: Genomic Landscape of EGFR Mutant NSCLC Prior to Erlotinib and at the Time of Disease Progression Following Erlotinib
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Carcinoma, Non-Small-Cell-Lung
Non-Small Cell Lung Cancer
Nonsmall Cell Lung Cancer
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2015-04-30
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

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.


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

Primary outcomes:
measure: 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
timeFrame: Up to 3 years
Secondary outcomes:
measure: Correlate mutations in signaling kinases with therapeutic response
timeFrame: Up to 3 years
measure: Correlate the allelic ratio of wild type to mutant EGFR with duration of response
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Daniel Morgensztern, M.D.
role: PRINCIPAL_INVESTIGATOR
References: