A Dose Escalation Study of BIBF 1120 Together With Paclitaxel and Carboplatin in Patients With Advanced Stage Non-small-cell Lung Cancer

Inclusion criteria

• Male or female patients with histologically or cytologically confirmed Stage IIIB (including pleural effusion), IV or recurrent NSCLC
• Bi-dimensionally measurable disease by one or more techniques (CT, MRI, X-ray)
• Age 18 years or older
• Life expectancy of at least three (3) months
• Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1
• Written informed consent that is consistent with ICH-GCP guidelines

Exclusion criteria

• Prior treatment for NSCLC including chemotherapy, biologic response modifier therapy, or any investigational drug
• Participation in another clinical study within the past four weeks before start of therapy or concomitantly with this study
• Active brain metastases (stable for <28 days, symptomatic, or requiring concurrent steroids or antiepileptic therapy)
• Centrally located tumors with radiologic evidence (CT or MRI) of local invasion of major blood vessels
• Cavitary or necrotic tumors
• Sanguinous pleural effusion due to disease or pericardial effusion suspicious for disease
• Radiotherapy to an area of measurable disease (unless disease progression had been documented following completion of therapy)
• Radiotherapy within 4 weeks preceding Day 0
• Other active malignancy diagnosed within the past 3 years (other than non-melanomatous skin cancer)
• Gastrointestinal abnormalities that would interfere with intake or absorption 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, ≥NYHA Grade 2 congestive heart failure)
• History of hemorrhagic or thrombotic event (including transient ischemic attacks) in the past 12 months
• Clinically significant hemoptysis (1 teaspoon or more) in the past 3 months
• Concurrent therapeutic anticoagulation (except heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except chronic low-dose daily aspirin <325 mg)
• Known hypersensitivity to paclitaxel, carboplatin, or any of their excipients including Cremophor® (polyoxyethylated castor oil)
• Absolute neutrophil count (ANC) ≤1,500/μl, platelet count ≤100,000/μl, or hemoglobin <9 gm/dL
• Total bilirubin >1.5 mg/dL (26 μmol/L, SI Unit equivalent), alanine amino transferase (ALT) and/or aspartate amino transferase (AST) ≥1.5 X ULN,
• Serum creatinine >1.5 mg/dL (>132 μmol/L, SI Unit equivalent)
• 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 breastfeeding
• Known or suspected active alcohol or drug abuse
• Patients unable to comply with the protocol