Sunitinib Malate as Maintenance Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer Previously Treated With Combination Chemotherapy

PRIMARY OBJECTIVES:

I. To evaluate the effect of sunitinib (sunitinib malate) compared to placebo on
progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients who
have had either stable or responding disease over the course of their initial 4 cycles of
platinum-based therapy.

SECONDARY OBJECTIVES:

I. To evaluate the toxicity of sunitinib compared to placebo in the maintenance setting.

II. To evaluate the additional response rate as a result of sunitinib in this setting.

III. To assess the impact of sunitinib on overall survival compared to the placebo arm.

IV. To assess the impact of sunitinib on delaying the time to deterioration in quality of
life and symptom progression compared to placebo using the European Organization for Research
and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and Lung Cancer
Module (LC13).

V. To assess vascular endothelial growth factor (VEGF) haplotypes in advanced non-small cell
lung cancer and sunitinib maintenance.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-21. Courses
repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO QD on days 1-21. Courses repeat every 21 days in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year,
every 6 months for 1 year, and then periodically for 3 years.

Inclusion Criteria:

- Histologic or cytologic documentation of primary non-small cell lung cancer

- Stage IIIB or IV disease patients who are not candidates for combined modality therapy
(chemoradiotherapy)

- No evidence of symptomatic or untreated brain metastases, spinal cord compression, or
carcinomatous meningitis; patients with central nervous system (CNS) metastases must
be asymptomatic, must have received definitive therapy (>= 6 weeks since resection or
>= 2 weeks since radiotherapy) for brain metastases, and be off steroids or on a
stable dose for 2 weeks prior to registration

- No cavitary lesions

- Patients must have received one chemotherapy regimen for stage IIIB or IV NSCLC; the
regimen must include four cycles of platinum-based doublet chemotherapy with or
without bevacizumab (bevacizumab may not be given beyond the fourth cycle of
chemotherapy); patients must have achieved a complete response, partial response, or
stable disease to first-line chemotherapy and have no evidence of disease progression;
patients will be registered 3-5 weeks following day 1 of cycle 4 of prior therapy

- No prior adjuvant chemotherapy for stage I-III resected NSCLC or combined modality
therapy for stage III NSCLC

- No other primary therapy (including experimental therapy) for NSCLC; palliative
radiation therapy must have been completed at least one week before planned start of
protocol therapy

- Patients must have measurable or non-measurable disease

- Measurable disease: lesions that can be accurately measured in at least one
dimension (longest diameter to be recorded) as >= 2 cm with conventional
techniques or as >= 1 cm with spiral computed tomography (CT) scan

- Non-measurable disease: all other lesions, including small lesions (longest
diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan) and
truly non-measurable lesions; lesions that are considered non-measurable include
the following:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural/pericardial effusion

- Lymphangitis cutis/pulmonis

- Abdominal masses that are not confirmed and followed by imaging techniques

- Cystic lesions

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Non-pregnant and non-nursing

- No ongoing cardiac dysrhythmias, atrial fibrillation, or history of corrected QT (QTc)
interval >= 500 msec (within 2 years prior to registration); the use of agents with
proarrhythmic potential (e.g., quinidine, procainamide, disopyramide, sotalol,
probucol, haloperidol, risperidone, indapamide, flecainide) is not recommended while
on protocol therapy

- Patients with class I New York Heart Association (NYHA) heart failure are eligible;
patients with a history of class II NYHA heart failure are eligible, provided they
meet at least one of the following criteria:

- Patients with a history of class II heart failure who are asymptomatic on
treatment

- Patients with prior anthracycline exposure

- Patients who have received central thoracic radiation that included the heart in
the radiotherapy port

- Patients with a history of class III or IV NYHA heart failure within 12 months prior
to registration are not eligible

- No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft or stenting, cerebrovascular accident or transient ischemic attack within the
last year

- Patients with hypertension that cannot be controlled by medications (> 150/100 mmHg
despite optimal medical therapy) are not eligible

- Patients who require use of therapeutic anticoagulation for thromboembolic disease are
not eligible; Note: low doses of coumadin (up to 2 mg daily) are permitted for
prophylaxis of thrombosis

- No history of venous thrombosis, pulmonary embolism, or hypercoagulopathy syndrome

- No history of pulmonary hemorrhage, bleeding diathesis, or evidence of hemoptysis;
patients with blood-tinged or blood-streaked sputum will be permitted on study if the
hemoptysis amounts to less than 5 ml of blood per episode and less than 10 ml of blood
per 24-hour period in the best estimate of the investigator

- Patients with a history of hypothyroidism are eligible, provided they are currently
euthyroid

- None of the following within 28 days of beginning treatment: abdominal fistula,
gastrointestinal perforation, intra-abdominal abscess, serious or non-healing wound,
ulcer, or bone fracture

- The following inhibitors of cytochrome P450 3A4 (CYP3A4) are prohibited within 7 days
before beginning and during treatment with sunitinib: azole antifungals (ketoconazole,
itraconazole), diltiazem, clarithromycin, erythromycin, verapamil, delavirdine, and
human immunodeficiency virus [HIV] protease inhibitors (indinavir, saquinavir,
ritonavir, atazanavir, nelfinavir); the following inducers of CYP3A4 are prohibited
within 12 days before beginning and during treatment with sunitinib: rifampin,
rifabutin, carbamazepine, phenobarbital, phenytoin, St. John's Wort, efavirenz,
tipranavir; other inhibitors and inducers of CYP3A4 may be used if necessary, but
their use is discouraged

- Patients unable to take oral medication are not eligible

- Granulocytes >= 1,500/mcl

- Platelet count >= 100,000/mcl

- Total bilirubin =< 1.5 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)=< 2.5 x ULN;
patients with liver metastases may have AST and ALT =< 5 x ULN; all other patients
will have AST and ALT =< 2.5 x ULN

- Creatinine =< 1.5 mg/dl