Cabozantinib-S-Malate and Erlotinib Hydrochloride in Treating Patients With Previously Treated Metastatic Non-Small Cell Lung Cancer
|Recurrent Non-Small Cell Lung Carcinoma Stage IV Non-Small Cell Lung Cancer||Drug: Cabozantinib S-malate Drug: Erlotinib Hydrochloride Other: Laboratory Biomarker Analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Phase II Trial of XL184 (Cabozantinib) Plus Erlotinib in Patients With Advanced EGFR-Mutant Non-small Cell Lung Cancer (NSCLC) Who Have Progressed on Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Therapy|
- Objective response defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to 2 years ]All radiographic responses will be presented as waterfall plots.
- Incidence of toxicities, graded according to the National Cancer Institute CTCAE v4.0 [ Time Frame: Up to 2 years ]Type, severity, time of onset, duration, and outcome of toxicities will be tabulated.
- Progression-free survival [ Time Frame: Up to 2 years ]Summarized with Kaplan-Meier plots.
- Radiographic response, evaluated by RECIST v1.1 [ Time Frame: Up to 2 years ]Presented as waterfall plots.
- Time to treatment failure [ Time Frame: Up to 2 years ]Summarized with Kaplan-Meier plots.
- Tumor growth rate [ Time Frame: Up to 2 years ]Estimated using an exponential growth model, providing a straight-forward estimate of the tumor doubling times.
- Changes in EGFR mutations [ Time Frame: Baseline up to 6 months after last study treatment ]
- Changes in HGF levels [ Time Frame: Baseline up to 6 months after last study treatment ]
- Changes in MET amplification [ Time Frame: Baseline up to 6 months after last study treatment ]
- Changes in VEGF levels [ Time Frame: Baseline up to 6 months after last study treatment ]
|Actual Study Start Date:||May 20, 2013|
|Estimated Primary Completion Date:||December 31, 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (cabozantinib-s-malate, erlotinib hydrochloride)
Patients receive cabozantinib-s-malate PO daily and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Cabozantinib S-malate
Other Names:Drug: Erlotinib Hydrochloride
Other Names:Other: Laboratory Biomarker Analysis
I. To evaluate for efficacy by response rate (RR) when patients with advanced non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation who have progressed following EGFR tyrosine kinase inhibitor (TKI) therapy are treated with XL184 (cabozantinib [cabozantinib-s-malate]) and erlotinib (erlotinib hydrochloride).
I. Determine progression free survival (PFS) for combination XL184 (cabozantinib) and erlotinib in EGFR mutation positive patients following progression on erlotinib.
II. Assess overall survival. III. Evaluate change in tumor growth rate on XL184 (cabozantinib) and erlotinib.
IV. Evaluate type, severity, duration and outcome of toxicities. 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.
Patients receive cabozantinib-s-malate orally (PO) daily 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 every 12 weeks for 1 year and then annually thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01866410
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|USC / Norris Comprehensive Cancer Center|
|Los Angeles, California, United States, 90033|
|University of California Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|City of Hope South Pasadena|
|South Pasadena, California, United States, 91030|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center|
|Hershey, Pennsylvania, United States, 17033-0850|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Karen Reckamp||City of Hope Comprehensive Cancer Center|