Monotherapy Pazopanib in Subjects With Advanced Non-Small Cell Lung Cancer

A Phase II, Non-randomized, Multi-center Study to Evaluate the Efficacy and Safety of Pazopanib (GW786034) in Subjects With Advanced Non-Small Cell Lung Cancer

This study is designed to evaluate the efficacy and safety of monotherapy pazopanib (a small molecule tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGF, and c-kit) in subjects with advanced (Stage IIIB or IV) non-small cell lung cancer.

Study 109609 is a single-arm, non-randomized, single-stage Phase II study of pazopanib in subjects with Stage IIIB or IV non-small cell lung cancer who have progressed after one or two prior regimens of systemic therapy. The study will be conducted at a limited number of institutions in the US. A total of 40 evaluable subjects will be enrolled and treated. Pazopanib will be given at a dose of 800mg (as determined by previous Phase I studies) orally once per day. Subjects may continue to receive study drug for up to two years unless they experience disease progression or withdraw from treatment for other reasons, or unless the Sponsor terminates the study. A rollover study may be available to those subjects who are exhibiting clinical benefit (stable disease or better). Evaluable subjects will be assessed for response as the primary endpoint.

Inclusion Criteria:

• Signed consent
• Histologically- or cytologically confirmed diagnosis of Stage IIIB or IV non-small cell lung cancer.
• Failed no more than two prior chemotherapy regimens for Stage IIIB or IV non-small cell lung cancer, including a platinum-containing regimen.
• Brain metastases permitted if subject has been treated with surgery and/or radiation therapy more than 4 weeks prior to date of first dose and is stable for at least one week off steroids.
• 18 years of age or older.
• Eastern Cooperative Oncology Group performance status of at least 2.
• Measurable disease according to RECIST.
• Adequate organ system function.
• Females may be eligible to enroll if they are of non-childbearing potential (surgically sterile or post-menopausal)or are using appropriate contraception methods.

Exclusion Criteria:

• Prior malignancy - unless disease-free for at least 3 years, or have had completely resected non-melanomatous skin cancer or successfully treated in situ carcinoma.
• History or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis, except for subjects with previously-treated CNS metastases, who are asymptomatic, and have had no requirement for steroids or anti-seizure medication for one week prior to first dose of study drug.
• Clinically significant gastrointestinal abnormalities.
• Presence of uncontrolled infection.
• Corrected QT interval greater than 480 msec.
• History of significant cardiovascular condition(s).
• Poorly controlled hypertension (systolic blood pressure of 140mmHG or greater or diastolic blood pressure of 90mmHg or greater).
• History of cerebrovascular accident, pulmonary embolism, or insufficiently treated deep venous thrombosis within the past 6 months prior to first dose of study drug.
• Major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
• Active bleeding or diathesis.
• Hemoptysis in excess of 2.5mL within 8 weeks of first dose of study drug.
• Serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance with study procedures.
• Use of prohibited medications as defined in protocol.
• Use of an investigational agent, including an investigational anti-cancer agent within 28 days, or 5 half-lives, whichever is longer, prior to first dose of study drug.
• Prior use of any investigational or licensed anti-angiogenic agent, including thalidomide and agents that target platelet-derived growth factor. Prior treatment with bevacizumab or epidermal growth factor receptor tyrosine kinase inhibitors