Erlotinib Hydrochloride and Cabozantinib-s-Malate Alone or in Combination as Second or Third Line Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer
Trial ID or NCT#
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.
A Randomized Phase II Trial of Erlotinib, Cabozantinib, or Erlotinib Plus Cabozantinib as 2nd or 3rd Line Therapy in Patients With EGFR Wild-Type NSCLC
- - INCLUSION CRITERIA STEP 1: - Cytologically or histologically confirmed non-small cell lung carcinoma (NSCLC) - Predominant non-squamous histology (patients with NSCLC not otherwise specified [NOS] are eligible); mixed tumors will be categorized by the predominant cell type; if small cell elements are present the patient is ineligible - Stage IV disease (includes M1a, M1b, or recurrent disease), according to the 7th edition of the lung cancer TNM classification system - Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria; baseline measurements and evaluation of all sites of disease must be obtained within 4 weeks prior to registration - Prior to registration, the investigator/site must confirm that sufficient pathology material representative of patient's cancer is available for submission for MET immunohistochemical (IHC) testing - Patients must have received one or two lines of prior chemotherapy (first line platinum-doublet based chemotherapy plus switch maintenance chemotherapy counts as one line of therapy); prior adjuvant chemotherapy for early stage disease does not count as one line of therapy if 12 months or greater elapsed between completion of adjuvant therapy and initiation of first-line systemic therapy; if less than 12 months elapsed, adjuvant chemotherapy counts as one line of therapy - Any prior chemotherapy (based on administration schedule) must have been completed in greater than or equal to the time frames specified in the protocol - Patients must have discontinued treatment with any other type of investigational agent >= 4 weeks prior to registration - Patients must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) v 4.0 =< grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs) - Patients with no known brain metastasis at baseline must have baseline brain imaging within 12 weeks prior to study registration not demonstrating brain metastases; patients with brain metastases at baseline must have baseline brain imagining within 4 weeks prior to study registration and meet all of the specific criteria for brain mets listed in the protocol - Radiation related toxicities must have resolved to =< grade 1 prior to registration - Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status between 0-2 - Patients must have an anticipated life expectancy greater than 3 months - Acceptable bone marrow, renal and hepatic function within 2 weeks prior to registration as defined in the protocol - Patients must have corrected QT interval calculated by the Fridericia formula (QTcF) =< 500 ms within 28 days before registration - Patients must be able to swallow tablets - INCLUSION CRITERIA STEP 2: - Patients must have met all eligibility requirements for Step 1 at time of registration to Step 1 to be eligible for Step 2 - Patients must have radiographic progressive disease per RECIST v1.1 criteria after >= 2 courses of therapy on Arm A or Arm B - Patients must be registered to Step 2 within 4 weeks of the last dose of treatment administration from Step 1 - Patients must have an ECOG performance status between 0-2 - Patients must have recovered to baseline (pre-Step 1) or CTCAE version 4.0 <= grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs
- - EXCLUSION CRITERIA STEP 1: - Patients without sufficient pathology material representative of the patient's cancer (tumor block or 10 unstained slides) - Prior erlotinib, other EGFR tyrosine kinase inhibitor therapy, vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor therapy, Met tyrosine kinase inhibitor therapy, or Met monoclonal antibody (MetMAb); prior antibody therapy such as bevacizumab or cetuximab is allowed with a washout period depending on dosing interval and investigational nature - Prior radiation therapy to the thoracic cavity, abdomen, or pelvis within 3 months prior to registration, to bone or brain metastasis within 14 days prior to registration, or to any other site within 28 days prior to registration - History of the following: Clinically-significant gastrointestinal (GI) bleeding within 6 months prior to registration; Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood within 3 months prior to registration; Any other signs indicative of pulmonary hemorrhage within 3 months prior to registration - Radiographic or other evidence of the following within 28 days prior to registration: • Tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor; Cavitating pulmonary lesion(s); Tumor in contact with, invading or encasing any major blood vessels - Psychiatric illness/social situations that would limit compliance with study requirements - History of major thrombotic events (deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 6 months prior to registration - Concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, low molecular weight heparin (LMWH), thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel). (low dose aspirin [=< 81 mg/day] and prophylactic LMWH are permitted) - Concomitant treatment of strong cytochrome P450 3A4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort) - Cardiovascular disorders including: Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening; - Concurrent uncontrolled hypertension; Any history of congenital long QT syndrome; Any of the following within 6 months prior to registration: - Unstable angina pectoris - Clinically-significant cardiac arrhythmias - Stroke (including transient ischemic attack [TIA], or other ischemic event) - Myocardial infarction - GI disorders particularly those associated with a high risk of perforation or fistula formation specified in the protocol - Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months prior to registration - Uncontrolled, significant, intercurrent or recent illness - Prior malignancy within 2 years prior to registration which required systemic treatment or is currently active - Pregnant or breast-feeding - Patients with known human immunodeficiency virus (HIV) disease taking antiretroviral therapy - Known chronic active hepatitis B - EXCLUSION CRITERIA (STEP 2): - Intervening anticancer treatment or major surgical procedure(s) between Step 1 and Step 2, except palliative radiation to the bone finishing >= 2 weeks prior to registration to Step 2 - Central nervous system (CNS) progression; patients with stable CNS disease are allowed - Intercurrent illness or disease complication that the investigator believes would limit the ability to safely tolerate the combination of erlotinib and cabozantinib
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