This phase II trial studies early onset pulmonary events in patients with non-small lung cancer and other cancers taking brigatinib or other TKIs. Severe side effects, including trouble breathing, coughing, pneumonia, and inflammation of the lungs (pneumonitis), have been seen in patients taking brigatinib. This study is being done to watch patients taking brigatinib and compare that experience with patients taking other drugs that also target ALK or ROS1 to study how often events like these occur. This study is also being done to observe patients who stopped brigatinib temporarily because of a suspected early onset pulmonary event, but then restarted brigatinib at the same dose to assess what experience they have.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03389399.
PRIMARY OBJECTIVE:
I. To estimate the incidence of early onset pulmonary events (EOPEs), defined as the proportion of participants with a peak reduction in diffusion capacity of the lung for carbon monoxide (DLCO) of 20% or greater after commencing brigatinib at 90 mg once daily (QD) or other ALK-/ROS1-targeted tyrosine kinase inhibitor (TKI) (‘other TKI’ from now on).
SECONDARY OBJECTIVES:
I. To quantify percentage change in DLCO from baseline after commencing brigatinib 90 mg QD or ‘other TKI’.
II. To quantify changes in 6 minute walking distance from baseline after commencing brigatinib or ‘other TKI’.
III. To quantify change in oxygen saturation on exertion from baseline after commencing brigatinib or ‘other TKI’.
IV. To measure change in dyspnea on exertion from baseline after commencing brigatinib or ‘other TKI’.
V. To measure other pulmonary function parameters as measured by pulmonary function test and imaging changes on computed tomography (CT) scanning chest before and after commencing brigatinib or ‘other TKI’.
VI. To correlate baseline / on treatment systemic inflammatory signatures, immunologic phenotype (e.g., HLA-phenotype), clinical, demographic, and molecular characteristics of participants with change in pulmonary function estimates (e.g., DLCO) as a means to discover the mechanism and/or predictive marker of EOPE.
OUTLINE:
Patients complete pulmonary function test, 6-minute walk test, and breathing questionnaire at baseline and days 2, 8, and 15 after starting treatment. Patients also undergo collection of blood samples at baseline and days 2 and 8 after starting treatment.
Lead OrganizationUniversity of Colorado
Principal InvestigatorRoss Camidge