This phase II trial studies how well cabozantinib-s-malate and erlotinib hydrochloride works in treating patients with previously treated metastatic non-small cell lung cancer. Cabozantinib-s-malate and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cabozantinib-s-malate may also stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. Giving cabozantinib-s-malate together with erlotinib hydrochloride may be an effective treatment for non-small cell lung cancer.
Name: Cabozantinib S-malate
Name: Erlotinib Hydrochloride
Name: Laboratory Biomarker Analysis
Description: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Measure: Objective Response Rate Time: Up to 2 yearsDescription: Tumor doubling time was estimated using an exponential growth model. Specifically, the pre-progression scan, and the baseline scan were used to estimate the doubling time prior to enrollment, td = log(2)∗1time/1log(tumor size) [derivation, S(t) = S(to)∗2∧[(t−to)/td] for a parameterization of exponential growth with a doubling time of td. Taking the logarithm on both sides: log(S(t))-log(S(to)) = log(2)∗(t − to)/td or td = log(2)∗(t − to)/[log(S(t))-log(S(to))] = log(2)∗1time/1log(S)], the baseline scan and first evaluation scan were used to determine the doubling time. Based on pre-planned protocol assessment, we estimated the percent of patients that experienced a slowing of tumor kinetics (a 30% increase in the length of time for tumor doubling) based on RECIST v1.1 measurements. Patients who did not get a scan on study, and patients whose pre-progression scans were missing or whose pre-progression tumor size was zero or whose tumor was decreasing prior to enrollment were excluded.
Measure: Percentage of Patients With a Greater Than 30% Increase in Tumor Doubling Time Time: Up to 2 yearsDescription: Grade 3 & 4 adverse events attributed to treatment agents. Events are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Measure: Number of Adverse Events Time: Up to 2 yearsDescription: Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD), ≥ 20% increase in the sum of the longest diameter of target lesions compared with the smallest-sum longest diameter recorded or the appearance of one or more new lesions; Stable Disease (SD), Neither CR, PR or PD.
Measure: Best Response Patient Count Time: Up to 2 yearsDescription: Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measure: Progression-free Survival Time: Until disease progression or death from any cause, up to 2 yearsDescription: Estimated using the product-limit method of Kaplan and Meier.
Measure: Overall Survival Time: Until death from any cause, up to 2 yearsDescription: Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. DNA was analyzed for the presence of the T790M point mutation.
Measure: Progression-free Survival by T790M Mutation Status Time: Until disease progression or death from any cause, up to 2 yearsDescription: Estimated using the product-limit method of Kaplan and Meier.
Measure: Overall Survival by T790M Mutation Status Time: Until death from any cause, up to 2 yearsAllocation: N/A
Single Group Assignment
There is one SNP
Estimated using the product-limit method of Kaplan and Meier.. Progression-free Survival by T790M Mutation Status. --- T790M ---
DNA was analyzed for the presence of the T790M point mutation.. Overall Survival by T790M Mutation Status. --- T790M ---
DNA was analyzed for the presence of the T790M point mutation.. Overall Survival by T790M Mutation Status. --- T790M --- --- T790M ---
V. Correlate outcome with tumor biomarkers such as met proto-oncogene (MET) amplification, T790M mutation, and serum markers of the vascular endothelial growth factor (VEGF) and MET pathways in a preliminary manner. --- T790M ---