Clinical trial NCT02554591: Genomic Landscape of Ceritinib
Official title: Retrospective Analysis of Genomic Landscape of ALK Positive NSCLC Prior to Ceritinib, and at Disease Progression Following Ceritinib
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Carcinoma, Non-Small-Cell Lung
Non-small Lung Cancer
Non-Small Cell Lung Cancer
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2015-09-18
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Genetic changes associated with disease progression following treatment with ceritinib
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 ALT to ALK gene rearrangement (roughly corrected for intrinsic difference 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: