Study of Pazopanib and Pemetrexed in Advanced Non-small Cell Lung Cancer

An Open-label, Multicentre, Randomised Phase II Study of Pazopanib in Combination With Pemetrexed in First-line Treatment of Subjects With Predominantly Non-squamous Cell Stage IIIBwet/IV Non-small Cell Lung Cancer

The main purpose of this study is to determine whether the combination of pazopanib and pemetrexed is safe and effective in the treatment of advanced non-small cell lung cancer (NSCLC).

Inclusion Criteria:

• Written informed consent
• At least 18 years old
• Histologically- or cytologically-confirmed diagnosis of predominantly nonsquamous cell Stage IIIBwet (with confirmed malignant pleural effusion) or Stage IV NSCLC
• No prior systemic first-line therapy for advanced NSCLC
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of at least 12 weeks
• Able to swallow and retain oral medication
• Adequate organ system function (hematological, hepatic, and renal)
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) OR childbearing potential, and agrees to use adequate contraception. A male with a female partner of childbearing potential is eligible if he uses a barrier method of contraception or abstinence during the study

Exclusion Criteria:

• Active malignancy or any malignancy in the 3 years prior to first dose of study drug other than NSCLC
• Central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for asymptomatic, previously treated CNS metastases
• Clinically significant gastrointestinal abnormalities
• Prolongation of corrected QT interval (QTc) > 480 msecs
• History of any one or more cardiovascular conditions within the past 6 months prior to randomization
• Poorly controlled hypertension
• History of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months
• Major surgery or trauma within 28 days or any non-healing wound, fracture, or ulcer
• Evidence of active bleeding or bleeding diathesis
• Recent hemoptysis
• Endobronchial lesions and/or lesions infiltrating major pulmonary vessels
• Serious and/or unstable pre-existing medical (e.g., uncontrolled infection), psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
• Use of any prohibited medication
• Use of an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug
• Ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity except alopecia
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib, pemetrexed, and/or cisplatin
• Inability to interrupt aspirin or other non-steroidal anti-inflammatory drugs during the study
• Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone
• Clinically significant third-space fluid collections (e.g., ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to study start
• Recent or concurrent yellow fever vaccination