Trametinib and Erlotinib Hydrochloride in Treating Patients with Stage IV or Recurrent Lung Cancer with EGFR Activating Mutation

Inclusion Criteria

• Pathologic evidence of advanced stage IV or recurrent lung adenocarcinoma reviewed at Memorial Sloan Kettering Cancer Center (MSKCC)
• Somatic activating mutation in EGFR radiographic progression during treatment with erlotinib or any other EGFR tyrosine kinase inhibitor (TKI) therapies
• Any number of prior chemotherapy regimens is permitted
• Measurable (Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]) indicator lesion not previously irradiated
• Karnofsky performance status (KPS) >= 70%
• Must have undergone biopsy after development of acquired resistance to erlotinib with available archived tissue (equivalent of >= 10 unstained slides)
• Left ventricular ejection fraction >= the lower limit of normal by echocardiogram (ECHO) or multigated acquisition scan (MUGA)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
• Total bilirubin =< 1.5 x ULN
• Albumin >= 2.6 g/dL
• Creatinine < 1.5 x ULN OR calculated creatinine clearance >= 50 mL/min
• Absolute neutrophil count (ANC) >= 1,200 cells/mm^3
• Hemoglobin >= 9.0 g/dL
• Platelets >= 100,000/mm^3

Exclusion Criteria

• Patients with symptomatic brain metastasis requiring escalating doses of steroids
• Patients with grade 2 or greater diarrhea prior to study initiation despite maximal medical management due to medications or a medical condition such as Crohn's disease or malabsorption
• Pregnant or lactating women
• Any type of systemic therapy (chemotherapy or experimental drugs) within 2 weeks of starting treatment on protocol except for a EGFR TKI
• Patients who have received prior treatment with a MEK inhibitor
• Any major surgery or extensive radiotherapy within 21 days of starting treatment on protocol
• A history of clinically significant interstitial lung disease or pneumonitis
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from day 1 of study administration, New York Heart Association class III or IV congestive heart failure, or symptomatic uncontrolled arrhythmias, prolonged corrected QT interval > 480 msec, treatment refractory hypertension, presence of a cardiac defibrillator
• History of central serous retinopathy or retinal vein occlusion
• Patients with baseline risk factors for central serous retinopathy or retinal vein occlusion such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mmHg
• History of prior malignancy within 3 years; patients who are considered no evidence of disease (NED) from a malignancy may be considered on a case by case basis
• Have a known immediate or delayed hypersensitivity reaction to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO)
• Any other condition that, in the opinion of the investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study