Pazopanib in Patients With Relapsed or Refractory Small Cell Lung Cancer

OBJECTIVES:

Primary

- To determine the progression-free survival rate in participants with relapsed or refractory
small cell lung cancer who have received one prior regimen of systemic chemotherapy at 8
weeks

Secondary

- To determine the response rate (as measured by RECIST 1.1 criteria and changes in blood
flow/perfusion as measured by perfusion CT)

- To determine median and overall survival

- To characterize the toxicity profile of pazopanib in this patient population.

Exploratory

- To analyze levels of circulating biomarkers from blood and urine samples obtained
serially throughout the study and assess the utility of individual or subsets of these
proteins to serve as a surrogate marker for treatment effect, treatment efficacy, and
for tumor progression

- To measure and investigate the use of monocytes as surrogate markers of angiogenesis
inhibition

- To analyze the subject population by identification of intra-tumoral biomarkers (such as
c-kit, VEGF receptors, and microvessel density measured in available tumor biopsies)
associated with the efficacy, safety and resistance to pazopanib

- To assess the utility of perfusion CT scan in evaluating changes in anti-angiogenic
activity as a measure of treatment efficacy

STATISTICAL DESIGN: This study uses a two-stage design to evaluate efficacy of cetuximab
based on progression-free rate (PFR) at week 8 defined as complete response (CR), partial
response (PR) or stable disease (SD) per RECIST 1.1 criteria. The null and alternative PFR
are 30% and 50%. If fewer than 4 patients enrolled in the stage one cohort (n=15 patients)
achieve SD or better than accrual would not proceed to stage two (n=15 patients). If 13 or
more patients are progression-free of the 30 patients then the null hypothesis will be
rejected. The probability that the treatment will be considered promising if the true PFR
rate was 30% is 8.4% and 82% if the true PFR rate was 50%.

Inclusion Criteria:

- Diagnosis of small cell neuroendocrine carcinoma based on either histology or cytology
with radiologically-confirmed progressive disease.

- Participants should have received first-line chemotherapy and may have had up to two
prior chemotherapy regimens. Radiation therapy may have been part of the permitted
prior therapy.

- Participants with brain metastases will be allowed if they have been treated with
surgery and/or radiation therapy more than 21 days prior, are asymptomatic, and are
stable for at least one week off steroids.

- 18 years of age or older

- ECOG Performance status of 0, 1 or 2

- Ability to swallow and retain oral medication

- Disease must be measurable according to RECIST 1.1

- Adequate organ function as defined in the protocol

Exclusion Criteria:

- Prior malignancy except for participants that have been disease-free for 3 years or
with a history of completely resected non-melanomatous skin carcinoma or successfully
treated in situ carcinoma

- History or clinical evidence of central nervous system metastases or leptomeningeal
carcinomatosis except for individuals who have previously-treated CNS metastases, 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

- Prolongation of corrected QT interval (QTc) > 480msecs

- History of any one or more of the following cardiovascular conditions within the past
6 months: cardiac angioplasty or stenting; myocardial infarction; unstable angina;
symptomatic peripheral vascular disease; Class III or IV congestive heart failure

- Poorly controlled hypertension

- History of cerebrovascular accident including transient ischemic attack, pulmonary
embolism or insufficiently treated deep venous thrombosis within the past 6 months

- Prior 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

- Evidence of active bleeding or bleeding diathesis

- Hemoptysis in excess of 2.5mL within 6 weeks of first dose of study drug

- Any serious and/or unstable pre-existing medical, 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 within the timeframes listed in the protocol

- Use of an investigational agent, including an investigational anti-cancer agent,
within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study
drug

- Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors

- Is now undergoing and/or has undergone in the 14 days immediately prior to first dose
of study drug, any cancer therapy

- Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is
progressing in severity

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to pazopanib