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
Overview
- Phase
- Phase 2
- Intervention
- Cabozantinib S-malate
- Conditions
- Recurrent Non-Small Cell Lung Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 37
- Locations
- 7
- Primary Endpoint
- Objective Response Rate
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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.
Detailed Description
PRIMARY OBJECTIVES: 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). SECONDARY OBJECTIVES: 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. OUTLINE: 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histologically or cytologically confirmed non-small cell lung cancer harboring an EGFR mutation; NOTE: EGFR mutational status will be known and assays performed in Clinical Laboratory Improvement Amendments (CLIA) certified laboratories will be accepted
- •Patients should have tumor tissue available for retrieval; tissue blocks or unstained slides from the time of original diagnosis are acceptable if repeat biopsy is not indicated
- •Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
- •Patients must have received prior EGFR TKI therapy for metastatic disease and have documented evidence of radiologic disease progression while on EGFR TKI as treatment immediately prior to enrollment; (patients may have received prior chemotherapy, and retreatment with erlotinib is allowed)
- •Eastern Cooperative Oncology Group (ECOG) performance status =\< 1 (Karnofsky \>= 60%)
- •Leukocytes \>= 3,000/mcL
- •Absolute neutrophil count \>= 1,500/mcL
- •Platelets \>= 100,000/mcL
- •Total bilirubin =\< 1.5 × upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 × institutional upper limit of normal
Exclusion Criteria
- •The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 3 weeks, or nitrosoureas/ mitomycin C within 6 weeks before the first dose of study treatment
- •Prior treatment with XL184 (cabozantinib) or other MET/hepatocyte growth factor (HGF) inhibitor
- •The subject has received radiation therapy:
- •To the thoracic cavity, abdomen, or pelvis within 2 weeks before the first dose of study treatment, or has ongoing complications, or is without complete recovery and healing from prior radiation therapy
- •To bone or brain metastasis within 14 days before the first dose of study treatment
- •To any other site(s) within 28 days before the first dose of study treatment
- •The subject has received prior treatment with a small molecule kinase inhibitor or a hormonal therapy (including investigational kinase inhibitors or hormones) within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment; prior erlotinib is required and does not require a 14-day wash out
- •The subject has received any other type of investigational agent within 28 days before the first dose of study treatment
- •The subject has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =\< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs)
- •The subject has a primary brain tumor
Arms & Interventions
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.
Intervention: Cabozantinib S-malate
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.
Intervention: Erlotinib Hydrochloride
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.
Intervention: Laboratory Biomarker Analysis
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: Up to 2 years
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
Secondary Outcomes
- Percentage of Patients With a Greater Than 30% Increase in Tumor Doubling Time(Up to 2 years)
- Number of Adverse Events(Up to 2 years)
- Best Response Patient Count(Up to 2 years)
- Overall Survival(Until death from any cause, up to 2 years)
- Progression-free Survival(Until disease progression or death from any cause, up to 2 years)