Study of Motesanib (AMG 706) in Combination With Paclitaxel and Carboplatin for Advanced Non-Squamous Non-Small Cell Lung Cancer

Inclusion Criteria: Disease Related: 1. Histologically or cytologically confirmed, Stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC) (except diagnosis by sputum cytology only). Adenosquamous histology or an unclear histology subtype containing more than 10% squamous cells was not allowed. 2. No prior chemotherapy, molecularly-targeted therapy, or immunotherapy. Neoadjuvant and post-operative adjuvant therapy except chemotherapy with platinum agent completed 1 year prior to randomization was permitted. 3. Measurable or non-measurable lesion per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 criteria (except non-measurable lesion with malignant effusion only). 4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 5. Life expectancy of ≥ 3 months as documented by the Investigator. Demographic: Must have been 18 years of age or older at the time informed consent was obtained. Laboratory: 1. Hematological function, as follows: * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L. * Platelet count ≥ 100 x 10\^9/L and ≤ 850 x 10\^9/L. * Hemoglobin ≥ 9 g/dL. 2. Renal function, as follows: * Creatinine clearance (GFR) \> 40 mL/min (calculated by Cockcroft-Gault formula). * Urinary protein quantitative value of ≤ 30 mg in urinalysis or ≤ 1+ on dipstick unless total quantitative protein was \< 500 mg in a 24-hour urine sample. 3. Hepatic function, as follows: * Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) or AST \< 5 x ULN if liver metastases were present. * Alanine aminotransferase (ALT) ≤ 2.5 x ULN or ALT \< 5 x ULN if liver metastases were present. * Alkaline phosphatase (ALP) ≤ 2.0 x ULN or ALP \< 5 x ULN if liver or bone metastases were present. * Total bilirubin \< 1.5 x ULN. 4. Coagulation function, as follows: * Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1 x ULN. * International normalized ratio (INR) ≤ 1.5 x ULN. Ethical: Ability to give written informed consent. General: 1. Able to take oral medications. 2. Able to start protocol-directed therapy within 7 days from the date of randomization. Exclusion Criteria: Disease Related: 1. Symptomatic central nervous system metastases. Participants with asymptomatic brain metastases were eligible if definitive therapy had been administered (surgery and/or radiation therapy), there was no planned treatment for brain metastasis, and the participant was clinically stable and off corticosteroids for at least 2 weeks prior to randomization. Participants with asymptomatic brain metastases were also eligible if the participant did not need definitive therapy (surgery and/or radiation therapy) or corticosteroids according to the Investigator's judgement. 2. Palliative radiation therapy: * Radiation therapy within 28 days prior to randomization for central (chest). * Radiation therapy within 14 days prior to randomization for distant metastatic foci. 3. History of pulmonary hemorrhage or gross hemoptysis (approximately 3 mL of bright red blood or more) within 6 months prior to randomization. Medications: 1. Prior targeted therapies, including but not limited to: • AMG 706, inhibitors of vascular endothelial growth factor (VEGF) (eg, SU5416, SU6668, ZD6474, SU11248, PTK787, AZD2171, AEE-788, sorafenib, bevacizumab), or epidermal growth factor receptor (EGFR) (eg, panitumumab, cetuximab, gefitinib, erlotinib). 2. Any anticoagulation therapy within 7 days prior to randomization. The use of low-dose warfarin (≤ 2 mg daily) or low molecular weight heparin or heparin flushes for prophylaxis against central venous catheter thrombosis was allowed. 3. Known history of allergy or hypersensitivity reaction to paclitaxel or carboplatin. General: 1. History of arterial or venous thrombosis within 12 months prior to randomization. 2. History of bleeding diathesis or bleeding within 14 days prior to randomization. 3. Peripheral neuropathy ≥ Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. 4. Clinically significant cardiovascular disease within 12 months of randomization, including myocardial infarction, unstable angina, ≥ Grade 2 peripheral vascular disease, cerebrovascular accident, transient ischemic attack, percutaneous transluminal coronary angioplasty/stent, congestive heart failure or ongoing arrhythmias requiring medication. 5. Any kind of disorder that compromised the ability of the participant to comply with the study procedures. 6. Open wound, ulcer or fracture. 7. Active or any uncontrolled, infection or inflammatory disease requiring systemic treatment ≤ 14 days prior to randomization. 8. Diagnosed interstitial lung disease and/or significant interstitial shadow on the computerized tomography (CT) image. 9. Uncontrolled hypertension as defined by resting blood pressure \> 150/90 mmHg despite the use of an antihypertensive. 10. History (past/current) of other primary cancer unless: * Curatively resected non-melanomatous skin cancer. * Curatively treated cervical carcinoma in situ. * Other primary solid tumor curatively treated with no known active disease present and no curative treatment administered for the last 3 years. 11. Surgery: * Major surgical procedures within 28 days prior to randomization. * Minor surgical procedures within 14 days prior to randomization. * Failure to recover from prior surgery. * Placement of a central venous access device (including ports and tunneled or non-tunneled catheters) within 3 days in principle prior to randomization. * Core needle biopsy within 7 days prior to randomization. 12. Planned elective surgery while on the study treatment. 13. Not recovered from all previous therapies (ie, radiation, surgery and medications). AEs related to previous therapies must have been CTCAE Grade ≤ 1 at Screening or must have resolved to the participant's Baseline level prior to the most recent previous therapy (except alopecia). 14. Participation in therapeutic clinical trials or currently receiving other investigational treatment(s) within 30 days prior to randomization. 15. Pregnant (eg, positive human chorionic gonadotropin \[HCG\] test-urine or serum) or breast-feeding woman. 16. Any participant not consenting to use adequate contraceptive precautions, from informed consent until 6 months after the last treatment. 17. Known to be human immunodeficiency virus (HIV), hepatitis B surface (HBs) antigen or hepatitis C positive. Participants may have been HBs antigen (-) and HB core antibody (+) and /or HBs antibody (+) with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) (-). If HBs antigen (-) but HBV DNA (+), participant could be enrolled with concomitant antiviral treatment (entecavir or tenofovir). In case of hepatitis C virus (HCV) antibody (+) with HCV ribonucleic acid (-) and/or HCV core antigen (-), participants could be enrolled. Participant with HBs antigen (+) could be enrolled if AST and ALT were within ULN, and HBV DNA level was less than 3.0 Log. The participant must have received concomitant antiviral treatment (entecavir or tenofovir). Participants who were already on antiviral treatment at Screening were not eligible. 18. Known chronic hepatitis. 19. History of any medical or psychiatric condition or laboratory abnormality that, in the opinion of the Investigator, may have increased the risks associated with participation in the study or administration of investigational products (IPs) administration, or may have interfered with the interpretation of the results. 20. Previously randomized to this study. 21. Not available for follow-up assessments or unable to comply with study requirements.