Combination Chemotherapy With or Without Maintenance Sunitinib Malate (IND 74019; NSC 736511) For Untreated Extensive Stage Small Cell Lung Cancer: A Phase IB/Randomized Phase II Study

Inclusion Criteria:

- Histologically or cytologically confirmed small cell lung cancer

- Extensive-stage disease, defined as any of the following:

- Extrathoracic metastases

- Malignant pleural effusion

- Bilateral or contralateral supraclavicular adenopathy or contralateral
hilar adenopathy

- No limited-stage disease, defined as disease restricted to 1 hemithorax with
regional lymph node metastases, including hilar, ipsilateral and contralateral
mediastinal, and/or ipsilateral supraclavicular nodes

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by
conventional techniques OR ≥ 10 mm by spiral CT scan

- No nonmeasurable disease, including all of the following:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural or pericardial effusion

- Lymphangitis cutis/pulmonis

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

- Cystic lesions

- No history of spinal cord compression or carcinomatous meningitis

- No history of brain metastases

- CTC performance status 0-1 (phase I) OR 0-2 (phase II)

- Absolute granulocyte count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Creatinine clearance ≥ 70 mL/min

- Bilirubin ≤ 1.5 mg/dL

- AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN for patients with
liver metastases)

- PTT ≤ 1.5 ULN

- Not pregnant or nursing

- No current active second malignancy other than non-melanoma skin cancers

- No ongoing cardiac dysrhythmias or atrial fibrillation

- QTc interval < 500 msec

- No New York Heart Association (NYHA) class III-IV heart failure within the past 12
months

- NYHA class II heart failure allowed, provided all of the following criteria are
met:

- Asymptomatic on treatment

- Prior anthracycline exposure

- Received prior central thoracic radiotherapy that included the heart in the
radiotherapy port

- None of the following within the past year:

- Myocardial infarction

- Coronary or peripheral artery bypass graft or stenting

- Severe or unstable angina

- Cerebrovascular accident, including transient ischemic attack

- Pulmonary embolism

- No hypertension that cannot be controlled by medications (i.e., blood pressure >
150/100 mm Hg despite optimal medical therapy)

- No hemoptysis within the past 4 weeks

- Patients with blood-tinged or blood-streaked sputum are eligible if < 5 mL of
blood per episode and < 10 mL of blood/24 hours

- None of the following within the past 28 days:

- Abdominal fistula

- Gastrointestinal perforation

- Intra-abdominal abscess

- Serious or nonhealing wound

- Ulcer

- Bone fracture

- No prior chemotherapy for small cell lung cancer

- At least 1 week since prior radiotherapy

- At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the
following:

- Azole antifungals (e.g., ketoconazole, itraconazole)

- Diltiazem

- Clarithromycin

- Erythromycin

- Verapamil

- Delavirdine

- HIV protease inhibitors (e.g., indinavir, saquinavir, ritonavir, atazanavir,
nelfinavir)

- At least 12 days since prior and no concurrent CYP3A4 inducers, including any of the
following:

- Rifampin

- Rifabutin

- Carbamazepine

- Phenobarbital

- Phenytoin

- Hypericum perforatum (St. John's wort)

- Efavirenz

- Tipranavir

- No concurrent therapeutic doses of coumarin-derivative anticoagulants

- Doses ≤ 2 mg daily for prophylaxis of thrombosis allowed

- Concurrent low molecular weight heparin allowed provided PT INR ≤ 1.5

- No other concurrent chemotherapy

- No concurrent hormonal therapy

- Concurrent steroids for adrenal failure, hormones for non-disease-related
conditions (e.g., insulin for diabetes), or intermittent dexamethasone allowed