Clinical trial NCT02491775: Afatinib Genomic Landscape
Official title: Genomic Landscape of EGFR Mutant NSCLC Prior to Afatinib and at the Time of Disease Progression Following Afatinib
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Carcinoma, Non-Small-Cell Lung
Non-Small Cell Lung Cancer
Non-small Lung Cancer
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2015-07-08
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be selected from the Washington University School of Medicine and Barnes-Jewish healthcare system who previously consented to study HRPO (Human Research Protection Office)# 201305031 ("Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information from Patients with Thoracic Malignancies, Suspected Thoracic Malignancies, or Mesothelioma").

Brief summary: The investigators propose to conduct a pilot feasibility study of single agent afatinib in patients with previously untreated metastatic EGFR (epidermal growth factor receptor) mutant adenocarcinoma of the lung (NSCLC = non-small cell lung cancer) with the sole purpose of characterizing the genomic landscape before afatinib and at the time of disease progression.

Detailed description: The current proposal will include exome and transcriptome sequencing from blood collected at baseline along with tumor samples obtained prior to starting afatinib and at the time of disease progression (a total of two tissue samples and one blood sample per patient). The samples will be collected via consent to the IRB (Institutional Review Board) approved banking study "Tissue and Blood Acquisition for Genomic Analysis and Collection of Health Information from Patients with Thoracic Malignancies, Suspected Thoracic Malignancies, or Mesothelioma".

If carried out successfully, the proposed strategy very likely will lead to a larger and adequately powered study (perhaps using whole genome sequencing) 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.

Successful completion of the proposed study would enable future studies to fully harness the potential of emerging technologies to develop novel approaches to treat and even ideally prevent resistance to EGFR TKIs (tyrosine-kinase inhibitor) and other molecularly targeted therapies. This could serve as a template for other cancer types as well. Over time, this approach, broadly used, would create simultaneously, highly valuable annotated tumor specimens along with germ line DNA for high-throughput genomic studies to identify novel targets and their impact on the course of disease. Re-analyzing molecular changes in the tumor at the time of disease progression would likely be a new standard of care to guide salvage therapy.

Eligibility criteria: Inclusion Criteria/Exclusion Criteria:

* Diagnosis of metastatic stage IIIB/IV lung adenocarcinoma
* Presence of known sensitizing mutations in EGFR TK domain (exon 19 deletion and L858R)
* Absence of known resistant mutations in the EGFR TK domain (T790M)
* 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")
* No prior treatment for this malignancy
* No prior localized therapy to the biopsy site
* Planned treatment with standard of care afatinib at 40 mg QD (daily)
* Not pregnant or breastfeeding
* At least 18 years of age

Primary outcomes:
measure: Genetic changes associated with disease progression following treatment with afatinib
timeFrame: Estimated to be 1 year
Secondary outcomes:
measure: Types of mutations in signaling kinases associated with therapeutic response
timeFrame: Estimated to be 1 year
measure: Allelic ratio of wild type to mutant EGFR (roughly corrected for intrinsic differences in tumor cellularity) with duration of response
timeFrame: Estimated to be 1 year
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: Ramaswamy Govindan, M.D.
role: PRINCIPAL_INVESTIGATOR
References: