Pazopanib Hydrochloride or a Placebo in Treating Patients With Non-Small Cell Lung Cancer Who Have Received First-Line Chemotherapy

Brain metastases allowed provided they are controlled and the patient must present with a performance status (PS) of 0-1 after the 4 courses of chemotherapy and at least 1 week off steroids

No known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage, including any of the following:

* Large protruding endobronchial lesions in the main or lobar bronchi

* Endobronchial lesions in the segmented bronchi are allowed

* Lesions extensively infiltrating the main or lobar bronchi

* Minor infiltrations in the wall of the bronchi are allowed

* Lesions infiltrating major pulmonary vessels (contiguous tumor and vessels)

* Tumors touching but not infiltrating (abutting) the vessels are acceptable

PATIENT CHARACTERISTICS:

WHO performance status (PS) 0-2

* PS 2 capped at 15% of the study population

* Elderly population (i.e., \> 70 years old) capped at 15% and must be PS 0-1

Life expectancy ≥ 12 weeks

ANC ≥ 1.5 x 10\^9/L

Platelet count ≥ 100 x 10\^9/L

Hemoglobin ≥ 9 g/dL

PT or INR ≤ 1.2 times upper limit of normal (ULN)

PTT ≤ 1.2 times ULN

Bilirubin ≤ 1.5 times ULN

AST/ALT ≤ 2.5 times ULN

Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min

Urine protein:creatinine ratio ≤ 1 OR ≤ 1.0 g of protein by 24-hour urine collection

May only be randomized in this trial once

Not pregnant or nursing

Negative pregnancy test

Fertile patients must use effective contraception 2 weeks prior to, during, and for at least 1 month after completion of study therapy

Corrected QT interval (QTc) ≤ 480 msec on normal 12-lead ECG

* If QTc interval is \> 480 msec, then 2 additional ECGs should be obtained over a brief period of time (e.g., within 15-20 minutes) to confirm the abnormality and the average QTc interval will be determined from the 3 ECG tracings by manual evaluation and will be used to determine if the patient will be excluded from the study

No history of any 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

No NYHA class III-IV congestive heart failure (no class II, III, or IV for elderly patients)

LVEF normal

No other malignancy within the past 2 years except for non-small cell lung cancer

No poorly controlled hypertension, defined as blood pressure (BP) \> 140/90 mm Hg

* Initiation or adjustment of antihypertensive medications is permitted prior to study entry provided blood pressure is reassessed on two occasions that are separated by a minimum of 1 hour and the mean systolic BP/diastolic BP values must be ≤ 140/90 mm Hg

No cerebrovascular accident (at any time in the past), transient ischemic attack, deep venous thrombosis (DVT), or pulmonary embolism within the past 6 months

* Patients with recent DVT who have been treated with therapeutic anticoagulating agents and remained stable for at least 6 weeks are eligible

No hemoptysis within the past 6 weeks (patients with a history of hemoptysis associated with metastatic disease must undergo a bronchoscopy to rule out endobronchial lesions and patients with an endobronchial lesion will be excluded from the study)

No history of clinically significant gastrointestinal disorders, including any of the following:

* Malabsorption syndrome

* Major resection of the stomach or small bowel that could affect the absorption of the study drug

* Active peptic ulcer disease

* Known intraluminal metastatic lesions with risk of bleeding

* Inflammatory bowel disease

* Ulcerative colitis

* Other gastrointestinal conditions with increased risk of perforation

No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days

No evidence of active bleeding or bleeding diathesis

No trauma within the past 28 days

No nonhealing wound, fracture, or ulcer

No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib hydrochloride

No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

PRIOR CONCURRENT THERAPY:

See Disease Characteristics

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

At least 6 months since prior amiodarone

At least 14 days since prior CYP3A4 substrates

At least 2 weeks since prior palliative radiotherapy

No major surgery within the past 28 days

No prior multi-target tyrosine kinase inhibitor (TKI), bevacizumab, or cetuximab (as part of induction therapy)

Prior radical radiotherapy allowed provided it was at least 12 months from start of induction chemotherapy for metastatic disease

Concurrent anticoagulant therapy allowed provided the patient's PT, INR, or PTT is stable and within the recommended range for the desired level of anticoagulation

What this study is about