Cabozantinib-S-Malate and Erlotinib Hydrochloride in Treating Patients With Previously Treated Metastatic Non-Small Cell Lung Cancer
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.
Recurrent Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Drug: erlotinib hydrochloride
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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 ] [ Designated as safety issue: No ]All radiographic responses will be presented as waterfall plots.
- Tumor growth rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Estimated using an exponential growth model, providing a straight-forward estimate of the tumor doubling times.
- Incidence of toxicities, graded according to the National Cancer Institute CTCAE v4.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]Type, severity, time of onset, duration, and outcome of toxicities will be tabulated.
- Radiographic response, evaluated by RECIST v1.1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Presented as waterfall plots.
- Progression-free survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Summarized with Kaplan-Meier plots.
- Time to treatment failure [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Summarized with Kaplan-Meier plots.
- Changes in EGFR mutations [ Time Frame: Baseline up to 6 months after last study treatment ] [ Designated as safety issue: No ]
- Changes in MET amplification [ Time Frame: Baseline up to 6 months after last study treatment ] [ Designated as safety issue: No ]
- Changes in VEGF levels [ Time Frame: Baseline up to 6 months after last study treatment ] [ Designated as safety issue: No ]
- Changes in HGF levels [ Time Frame: Baseline up to 6 months after last study treatment ] [ Designated as safety issue: No ]
|Study Start Date:||May 2013|
|Estimated Primary Completion Date:||January 2015 (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.
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.
|United States, California|
|City of Hope||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Karen L. Reckamp 626-256-4673 firstname.lastname@example.org|
|Principal Investigator: Karen L. Reckamp|
|University of Southern California||Recruiting|
|Los Angeles, California, United States, 90033|
|Contact: Barbara J. Gitlitz 323-865-3959 email@example.com|
|Principal Investigator: Barbara J. Gitlitz|
|UC Davis Comprehensive Cancer Center||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: David R. Gandara 916-734-3771 firstname.lastname@example.org|
|Principal Investigator: David R. Gandara|
|City of Hope- South Pasadena Cancer Center||Recruiting|
|South Pasadena, California, United States, 91030|
|Contact: Stephen C. Koehler 626-396-2900 email@example.com|
|Principal Investigator: Stephen C. Koehler|
|United States, Michigan|
|Wayne State University-Karmanos Cancer Institute||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Shirish M. Gadgeel 313-576-8753 firstname.lastname@example.org|
|Principal Investigator: Shirish M. Gadgeel|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center||Recruiting|
|Hershey, Pennsylvania, United States, 17033-0850|
|Contact: Chandra P. Belani 717-531-1078 email@example.com|
|Principal Investigator: Chandra P. Belani|
|University of Pittsburgh Cancer Institute||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: Mark A. Socinski 412-623-4083 firstname.lastname@example.org|
|Principal Investigator: Mark A. Socinski|
|Principal Investigator:||Karen Reckamp||Beckman Research Institute|