Primary Outcomes

Description: OS is defined as the Time from randomization to death from any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier. Overall survival will be compared between the 2 treatment arms using the unstratified log-rank test.

Secondary Outcomes

Description: PFS is defined as the time from randomization to documentation of disease progression or death due to any cause, whichever is first. The distribution of progression free survival will be estimated using the method of Kaplan-Meier. Progression free survival will be compared between the 2 treatment arms using the log-rank test.

Description: Defined as the number of patients with a complete response (CR) or partial response (PR) (as defined by the Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) divided by the number of evaluable patients in each arm at 12 months post ranomization. ORR will be compared between the 2 treatment arms. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.

Description: Defined as the number of patients with a complete response (CR), partial response (PR), or stable disease for >= 6 months (as defined by the RECIST 1.1) divided by the number of evaluable patients in each arm. Confidence intervals for the true success proportion will be calculated according to the approach of Clopper and Pearson.

Description: The maximum grade for each type of adverse event will be recorded for each patient in each cycle. The overall adverse event rates for grade 3 or higher adverse events will be compared using Chi-Square or Fisher's Exact tests.

Description: Patients reported quality of life (QOL) outcomes will be collected using the Linear Analog Self-Assessment (LASA) Questionnaire. Data will be collected each cycle. Mean values of the first question (regarding overall QOL) at each cycle will be plotted, and stratified by arm. Additional analyses using data collected from the LASA questionnaire may be performed.

Other Outcomes

Description: A report will be generated for each clinical specimen, which may include (but not limited to) the presence or absence of relevant gene mutations or amplifications, along with the allele frequency. Mutations of interest include KRAS and NRAS exons 2, 3, and 4, BRAF, PIK3CA, EGFR, AKT, PTEN, MAP2K1, and MET. Amplifications of interest include MET, EGFR, KRAS, and ERBB2. Genes and alterations analyzed will be based on best available science at the time of analysis.

Description: Plasma samples will be analyzed for multiple soluble protein analytes, which may include (but not limited to) HGF, c-MET, EGF, HBEGF, TGF-alpha, EGFR, HER2, and CD73.

Description: Comprehensive mutational analysis will be performed on archived formalin fixed paraffin embedded (FFPE) tumor samples. This analysis may include, but is not limited to Next Generation Sequencing (NGS) and IHC where appropriate.