This phase I trial studies the side effects and best dose of c-Met inhibitor INCB028060 and erlotinib hydrochloride when given together in treating patients with previously treated non-small cell lung cancer. C-Met inhibitor INCB028060 and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of INC280 (c-Met inhibitor INCB028060) plus erlotinib (erlotinib hydrochloride) in patients with met proto-oncogene (MET) expressing non-small cell lung cancer (NSCLC). SECONDARY OBJECTIVES: I. To describe the toxicity profile of INC280 plus erlotinib. II. To determine the preliminary efficacy of INC280 plus erlotinib. III. To characterize the pharmacokinetic behavior of this combination. TERTIARY OBJECTIVES: I. To collect blood and tumor samples for exploratory analysis of the MET and epidermal growth factor receptor (EGFR) signaling pathways. OUTLINE: This is a dose-escalation study. Patients receive c-Met inhibitor INCB028060 orally (PO) twice daily (BID) and erlotinib hydrochloride PO once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Given PO
Given PO
University of California, Davis
Sacramento, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Maximum tolerated dose (MTD) of c-Met inhibitor INCB028060 and erlotinib, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize toxicities and side effects by dose and by course. Baseline information (e.g. the extent of prior therapy) and demographic information will be presented.
Time frame: Up to 28 days after a full course of therapy
Toxicities as measured by NCI CTCAE V4
The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course. Baseline information (e.g. the extent of prior therapy) and demographic information will be presented.
Time frame: Up to 30 days
Overall response rate among patients with measurable disease, measured by RECIST 1.1
Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals.
Time frame: Up to 30 days
Disease control rate, measured by RECIST 1.1
Time frame: Up to 30 days
Progression-free survival
Summarized with Kaplan-Meier plots. Median time to progression will be estimated using standard life table methods.
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Time frame: Duration of time from start of treatment to time of progression or death, assessed up to 30 days
Overall survival
Summarized with Kaplan-Meier plots. Median time to progression will be estimated using standard life table methods.
Time frame: Duration of time from the start of treatment to death from any cause, assessed up to 30 days
Concentrations of c-Met inhibitor INCB028060 in plasma, measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay
Time frame: Days 15-16 of course 1, days 1 and 15 of course 2, and day 1 of courses 3-4