This randomized phase II trial studies how well giving erlotinib hydrochloride and cabozantinib-s-malate alone or in combination works as second or third line therapy in treating patient with stage IV non-small cell lung cancer. Erlotinib hydrochloride and cabozantinib-s-malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving erlotinib hydrochloride together with cabozantinib-s-malate is more effective than erlotinib hydrochloride or cabozantinib-s-malate alone in treating non-small cell lung cancer.
PRIMARY OBJECTIVES: I. To compare the progression-free survival (PFS) associated with patients treated with erlotinib (erlotinib hydrochloride) versus (vs) erlotinib plus cabozantinib (cabozantinib-s-malate). II. To compare the PFS associated with patients treated with erlotinib vs cabozantinib. SECONDARY OBJECTIVES: I. To evaluate overall survival in the three treatment arms. II. To evaluate best objective response rate in the three treatment arms. III. To define the toxicity associated with each regimen. IV. To conduct correlative science studies that will help to select predictive biomarkers of response to therapy, including mesenchymal-epidermal transition (MET) expression and potentially other tissue biomarkers, plasma biomarkers, and bone scans. OUTLINE: Patients are randomized to 1 of 3 treatment arms. ARM A (erlotinib): Patients receive erlotinib orally (PO) daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B (cabozantinib): Patients receive cabozantinib PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM C (erlotinib+cabozantinib): Patients receive erlotinib as patients in Arm A and cabozantinib as patients in Arm B. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM Z: Patients achieving disease progression in Arm A or Arm B may receive erlotinib and cabozantinib as patients in Arm C. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
125
Given PO
Given PO
Correlative studies
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Memorial Medical Center
Modesto, California, United States
Community Hospital of Monterey Peninsula
Monterey, California, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
VA Palo Alto Health Care System
Palo Alto, California, United States
Progression-free Survival (PFS)
PFS is defined as the time from randomization to documented disease progression or death from any cause, whichever occurred first. Patients who had not experienced an event of interest by the time of analysis were censored at the date of last disease assessment.
Time frame: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years
Overall Survival (OS)
OS is defined as the time from randomization to death from any cause or date of last known alive.
Time frame: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years
Proportion of Patients With Objective Response
Objective response is defined as complete response (CR) or partial response (PR) evaluated using RECIST v 1.1. CR is defined as disappearance of all lesions and any pathological lymph nodes must have reduction in short axis to \< 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions and persistence of one or more non-target lesion(s).
Time frame: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry, up to 5 years
Proportion of Patients With MET Positivity
Submission of archival tissue for central MET IHC testing was required for this study, and total MET IHC testing was conducted at the Brigham and Women's Hospital using the c-Met clone CVD13 (arabbit polyclonal). Membranous and cytoplasmic staining were individually scored, and positivity was declared if MET was expressed in either the membrane or cytoplasm.
Time frame: Assessed at baseline
Proportion of Patients With Worst Grade Toxicities of Grade 3 or Higher
Time frame: Assessed every 4 weeks while on treatment and for 30 days after the end of treatment
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