An Open-label, Multicenter, Phase I/II Study of Pazopanib in Combination With Paclitaxel in First-line Treatment of Subjects With Stage IIIBwet/IV Non-small Cell Lung Cancer
Inclusion Criteria:
- Written informed consent
- At least 18 years old
- Histologically- or cytologically-confirmed diagnosis of Stage IIIBwet (with confirmed
malignant pleural effusion) or Stage IV NSCLC (or for Phase I only, advanced solid
tumor for which there is no standard therapy or for whom paclitaxel is standard
therapy).
- No prior systemic first-line therapy for advanced disease
- Measurable disease
- 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, renal, and hepatic)
- Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) OR
childbearing potential, and agrees to use adequate contraception
Exclusion Criteria:
- Active malignancy or any malignancy in the 3 years prior to first dose of study drug
other than NSCLC (or for Phase I, other than the primary solid tumor)
- 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, paclitaxel, and/or carboplatin.