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

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) meeting the following criteria:
• Any histology
• Stage IIIB-IV disease
• Newly diagnosed or recurrent disease (after surgery or radical radiotherapy) proven on cytology or histology before induction chemotherapy
• In case of adjuvant chemotherapy after previous surgery, time interval from start of previous treatment to induction chemotherapy for metastatic disease is 12 months
• May or may not have measurable disease as defined by RECIST criteria
• Must not have progressed during the 4 courses of initial chemotherapy
• For patient presenting with measurable disease, there must be documented radiographic evidence of response (complete response, partial response, or stable disease) according to RECIST 1.1 criteria
• For patients without measurable disease, there must be no symptomatic/clinical progression
• EGFR wild-type or unknown (known EGFR mutations are not eligible)
• 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