Dose Escalation of BIBF 1120 Combined With Pemetrexed in Advanced Non Small Cell Lung Cancer

Inclusion Criteria:

* Pathologic confirmation of metastatic, unresectable, or locally advanced NSCLC (non-small cell lung cancer)
* Disease progression during or following one prior platinum-based (including prior neoadjuvant or adjuvant therapy) chemotherapy regimen for advanced disease
* Bi-dimensionally measurable disease by one or more techniques (CT (computed tomography), MRI (magnetic resonance imaging), X-ray)
* Age 18 years or older
* Life expectancy of at least three (3) months
* Eastern Cooperative Oncology Group (ECOG) performance score 0-2
* Written informed consent that is consistent with ICH-GCP (International Conference on Harmonization - Good Clinical Practice) guidelines

Exclusion Criteria:

* Participation in another clinical study within the past 28 days prior to the start of therapy or concomitantly with this study
* Treatment for NSCLC (except radiotherapy for palliative reasons) within the past 28 days prior to Treatment Day 1 of this trial. All toxicities of the previous therapy must have resolved to baseline prior to Treatment Day 1
* Patient has received more than one prior chemotherapy regimen for advanced disease
* Radiotherapy to an area of measurable disease (unless disease progression had been documented following completion of therapy)
* Patients who are unwilling or unable to take folic acid and vitamin B12 supplementation
* Radiotherapy within 4 weeks prior to Treatment Day 1
* Prior treatment with agents that target the vascular endothelial growth factor (VEGF) pathways, including monoclonal antibody therapy (such as bevacizumab) or tyrosine kinase inhibitors
* Active brain metastases (stable for \<28 days, symptomatic, or requiring concurrent steroids or antiepileptic therapy). Patients who have received prior whole brain irradiation and whose brain metastases are stable according to the criteria above will not be excluded
* Centrally located tumors with radiologic evidence (CT or MRI) of local invasion of major blood vessels, with exception of those tumors which have received prior irradiation and are stable
* Cavitary or necrotic tumors
* Sanguinous pleural effusion due to disease or pericardial effusion suspicious for disease
* Other active malignancy diagnosed within the past 3 years (other than non-melanomatous skin cancer)
* Gastrointestinal abnormalities that would interfere with intake or absorption (with exception of patients with gastric esophageal reflux disease controlled with proton pump inhibitors) of the study drug, such as a requirement for intravenous alimentation, prior surgical procedures affecting absorption, treatment for peptic ulcer disease within the last 6 months, active gastrointestinal bleeding unrelated to cancer (as evidenced by either hematemesis, hematochezia, or melena in the past 3 months and without endoscopic documented resolution), or malabsorption syndromes
* Significant cardiovascular disease (i.e., uncontrolled hypertension, myocardial infarction within 6 months, unstable angina, serious cardiac arrhythmia, \>2 New York Heart Association (NYHA) Grade 2 congestive heart failure)
* History of hemorrhagic or thrombotic event (including transient ischemic attacks) in the past 12 months or clinically significant hemoptysis in the past 3 months
* Patients receiving any anti-coagulant therapy (including coumadin, heparin, low molecular weight heparin, and aspirin
* Patient has received prior therapy with pemetrexed
* Absolute neutrophil count (ANC) ≤1,500/μl, platelet count ≤100,000/μl, or hemoglobin \<9 gm/dL
* Total bilirubin \>1.5 mg/dL (26 μmole/L, SI-Unit equivalent), alanine amino transferase (ALT) and/or aspartate amino transferase (AST) ≥1.5 X upper limit of normal (ULN)
* Inadequate renal function determined by a serum creatinine level \>1.5 X ULN
* Patient is unable or unwilling to interrupt aspirin or other NSAIDS for a 5-day period (8 days period for long lasting agents like piroxicam)
* Persistent hematuria or proteinuria (more than trace)
* Women and men who are sexually active and unwilling to use a medically acceptable method of contraception
* Pregnancy or breast feeding
* Known or suspected active alcohol or drug abuse
* Patients unable to comply with the protocol