Genomic Landscape of Ceritinib

The Washington University

Status: Terminated

Conditions: Non-small Lung Cancer; Carcinoma, Non-Small-Cell Lung; Non-Small Cell Lung Cancer

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT02554591

201509030

Details and patient eligibility

About

The investigators propose to conduct a retrospective study of single agent ceritinib in patients with previously untreated anaplastic lymphoma kinase (ALK) rearranged adenocarcinoma of the lung with the sole purpose of characterizing the genomic landscape before ceritinib and at the time of disease progression.

Full description

Further improvements in therapy can only be achieved with a better understanding of the genomic landscape of ALK rearranged non-small cell lung cancer (NSCLC), specifically at the time of disease progression following treatment with ALK inhibitors. Recently, secondary ALK mutations, L1196M and G1269A have been described in patients with acquired resistance to crizotinib. A small subset of ALK positive lung cancer patients who progressed after treatment with ceritinib had tumors available for molecular analysis. Secondary mutations found included G1202R, F1174C, and F1174V. While this is interesting, an unbiased genomic study (exome or whole genome sequencing) using massively parallel sequencing at the time of disease progression is critical to fully understand the clonal evolution and the molecular mechanisms underpinning treatment resistance. To the best of the investigators' knowledge, such a study has not yet been reported.

The investigators believe the time is ripe now to comprehensively characterize genomic alterations using massively parallel sequencing technology of ALK driven adenocarcinoma of the lung to fully understand the clonal heterogeneity before therapy and fully understand the clonal evolution and the molecular mechanisms underpinning treatment resistance. A better understanding of genomic alterations through an unbiased comprehensive approach likely would lead to rationally designed therapy to augment response to ALK inhibitors.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• Diagnosis of metastatic stage IIIB/IV lung adenocarcinoma.
• Presence of known ALK gene rearrangement.
• 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") with an existing specimen prior to initiation of treatment with ceritinib.
• At least 18 years of age.
• Received treatment with standard of care ceritinib