Determination of Safety, Efficacy, and Pharmacokinetics of “Regorafenib” Combined With Pemetrexed and Cisplatin in Patients With Nonsquamous Non-Small Cell Lung Cancer

Inclusion Criteria:

Age >= 18 years.
Histological or cytological diagnosis of metastatic Stage IV or locally advanced, unresectable confirmed Stage IIIB nonsquamous Non-Small Cell Lung Cancer (NSCLC) not amenable to local therapy with curative intent.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2
Life expectancy of at least 12 weeks.
Adequate bone marrow, liver, and renal function
Controlled blood pressure [defined as systolic Blood Pressure (BP) <=150 mmHg and diastolic Blood Pressure (BP) <= 90 mmHg]
Men and women of childbearing potential enrolled in this study must use adequate barrier birth control measures during the course of the study

Exclusion Criteria:

Sensory neuropathy with sensory alterations or paresthesia (including tingling), interfering with function
Hearing impairment
Persistent proteinuria of Common Toxicity Criteria (CTC) Grade 3 or higher
Cardiac disease: congestive heart failure > New York Heart Association (NYHA) Class II; patients must not have unstable angina (anginal symptoms at rest) or new-onset angina (began within the last 3 months) or myocardial infarction within the past 6 months; cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
Brain metastasis: patients with neurological symptoms should undergo a Computerized Tomography (CT) scan / Magnetic Resonance Imaging (MRI) of the brain to exclude any new or progressive brain metastasis. Patients with brain metastases are excluded from the trial
Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication
Pulmonary hemorrhage/bleeding event > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 within 4 weeks prior to the start of study treatment. Clinically significant hemoptysis (1 teaspoon or more) in the past 3 months
Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks prior to the start of study treatment
Evidence or history of bleeding diathesis or coagulopathy
Centrally located tumors with radiologic evidence (CT or MRI) of local invasion of major blood vessels
The effect of third space fluid, such as pleural effusion and ascites, on pemetrexed is unknown. In patients with clinically significant third space fluid, consideration should be given to draining the effusion prior to study start
Patients with phaeochromocytoma Excluded Therapies and Medications, Previous and Concomitant
Prior treatment with a systemic chemotherapy for metastatic NSCLC. Patients who underwent prior systemic treatment or radiotherapy for NSCLC in a neoadjuvant or adjuvant setting are eligible, but no chemotherapy treatment within the last 6 month prior to study entry is allowed