A Non-Randomized, Multi-Center Open Label Phase II Study of Pazopanib and Pemetrexed or Pazopanib Alone In Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer After Progression on First Line Therapy Containing Bevacizumab.

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Cytologically or histologically confirmed stage IIIB (with malignant pleural or
pericardial effusion or supraclavicular lymph node involvement) or stage IV non-small
cell lung cancer

- Non-squamous histology

- Measurable disease using RECIST criteria

- Evidence of progression while on bevacizumab (documentation of radiographic
progression must be ≤ 8 weeks from last bevacizumab treatment)

- No lesions infiltrating major pulmonary vessels

- No significant uncontrolled pleural effusion, ascites, or other clinically
significant third space fluid collections

- No spinal cord compression, leptomeningeal carcinomatosis, or symptomatic and/or
untreated CNS metastasis

- Patients who were treated for CNS metastases are eligible provided they are
asymptomatic and have had no requirement for steroids within the past 2 weeks

- Anticonvulsants that have minimal drug interaction potential (i.e., levatiracem)
are allowed provided the patient has been on a stable dose for ≥ 4 weeks

- Screening with CNS imaging studies (CT scan or MRI) is required if clinically
indicated or if the patient has a history of CNS metastases

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- ANC ≥ 1,500/mm^3

- Hemoglobin ≥ 9 g/dL (5.6 mmol/L) (no transfusion within the past 7 days)

- Platelet count ≥ 100,000/mm^3

- PT or INR ≤ 1.5 times upper limit of normal (ULN)

- PTT ≤ 1.5 times ULN

- Total bilirubin ≤ 1.5 times ULN*

- AST and ALT ≤ 2.5 times ULN*

- Serum creatinine ≤ 1.5 mg/dL (133 μmol/L) OR calculated creatinine clearance ≥ 45
mL/min

- Urine protein to creatinine ratio < 1 OR < 1 g protein on 24-hour urine collection

- Corrected QT interval ≤ 480 msec

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Willing to provide blood samples for biomarker analysis

- Able to swallow and retain oral medication

- No clinically significant gastrointestinal (GI) abnormalities that may increase the
risk for GI bleeding including, but not limited to, any of the following:

- Active peptic ulcer disease

- Known intraluminal metastatic lesion(s) with risk of bleeding

- Active inflammatory bowel disease (e.g., ulcerative colitis, Crohn disease) or
other GI conditions with increased risk of perforation

- History of abdominal fistula, GI perforation, or intra-abdominal abscess within
the past 28 days

- No clinically significant GI abnormalities that may affect absorption of the study
drugs including, but not limited to, any of the following:

- Malabsorption syndrome

- Major resection of the stomach or small bowel

- No history of GI bleeding within the past 6 months

- No prior malignancy except for completely resected nonmelanomatous skin carcinoma or
successfully treated in situ carcinoma unless the patient has been disease-free for ≥
3 years

- No uncontrolled infection or nonhealing wound, fracture, or ulcer

- No history of any one or more of the following cardiovascular conditions within the
past 6 months:

- Cardiac angioplasty or stenting

- Myocardial infarction

- Unstable angina

- Coronary artery bypass graft surgery

- Symptomatic peripheral vascular disease

- NYHA class III or IV congestive heart failure

- No poorly controlled hypertension (defined as systolic BP ≥ 140 mm Hg or diastolic BP
≥ 90 mm Hg)

- Initiation or adjustment of antihypertensive medication(s) is allowed before
study entry

- No history of cerebrovascular accident including transient ischemic attack, pulmonary
embolism, or untreated deep venous thrombosis (DVT) within the past 6 months

- Patients with recent DVT who have been treated with therapeutic anticoagulating
agents for ≥ 6 weeks are eligible provided they are monitored regularly for
changes in relevant coagulation parameters, as clinically indicated, as well as
any clinical bleeding episodes

- No major trauma within the past 28 days

- No evidence of active bleeding or bleeding diathesis

- No hemoptysis within the past 6 weeks

- No serious and/or unstable pre-existing medical, psychiatric, or other condition that
could interfere with the patient's safety, provision of informed consent, or
compliance to study procedures NOTE: *No concurrent elevations in bilirubin and
AST/ALT above 1.0 times ULN

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No more than 1 prior cytotoxic chemotherapy regimen (platinum-containing) in
combination with bevacizumab

- Bevacizumab continued as a single agent after completion of cytotoxic therapy in
the first-line setting does not constitute a second regimen and is therefore
allowed

- If one or more of the agents in the patient's regimen had to be reduced,
omitted, or substituted with another similar drug due to toxicity, these changes
do not constitute a new regimen

- Last bevacizumab treatment must be within the past 3-9 weeks

- No prior exposure to anti-VEGF therapy except for bevacizumab

- No ongoing toxicity from prior anticancer therapy that is > grade 1 or baseline
and/or that is progressing in severity (except for alopecia)

- More than 28 days since prior major surgery (procedures such as catheter placement
are not considered to be major)

- More than 14 days since prior radiotherapy, surgery, or tumor embolization

- More than 14 days or 5 half-lives (whichever is longer) since prior chemotherapy,
immunotherapy, biologic therapy, investigational therapy, or hormonal therapy

- More than 14 days since prior steroids

- Patients with a creatinine clearance of 45-79 mL/min who are otherwise eligible for
treatment in group 2 but are on daily treatment with NSAIDs are not eligible unless
they can interrupt NSAIDs with short-elimination half-lives 2 days before (5 days for
NSAIDs with longer half-lives), the day of, and 2 days after administration of
pemetrexed disodium

- At least 14 days since prior and no concurrent medications (substrates of CYP3A4,
CYP2C8, and CYP2D6) with a narrow therapeutic window

- These medications may be resumed 7-15 days after the last dose of pazopanib
hydrochloride

- No concurrent strong CYP3A4 inhibitors

- No concurrent CYP3A4 inducers