S0802 – Topotecan With or Without Aflibercept in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Inclusion Criteria:

Histologically or cytologically confirmed extensive stage small cell lung cancer

Progressive or recurrent disease following one (and only one) standard first-line platinum-containing regimen (cisplatin or carboplatin)

Measurable or non-measurable disease per RECIST criteria

Disease must be outside a previously irradiated field OR a new lesion must be inside the irradiated field
Disease must be outside a previously resected area OR a new lesion must be present
No known brain metastasis unless the metastasis has been treated and is stable for ≥ 3 months prior to study entry
No leptomeningeal involvement or brain stem metastasis
Zubrod performance status 0-1
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 10 g/dL
Serum creatinine ≤ 1.5 times upper limit of normal OR creatinine clearance ≥ 60 mL/min
Urine protein: creatinine ratio < 1 OR urine protein < 500 mg by 24-hour urine collection
Not pregnant or nursing
Fertile patients must use effective contraception
Willing to provide smoking history
No evidence of active infection
No active bleeding
No significant history of bleeding diathesis, including hemoptysis (½ teaspoon of hemoptysis within the past 3 months), or underlying coagulopathy

No history of recent arterial embolic events, including any of the following:

Myocardial infarction
Cerebrovascular accident
Transient ischemic attack
Worsening of pre-existing angina within the past 6 months

No uncontrolled hypertension (systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg)

History of hypertension allowed provided it is controlled on anti-hypertensive medications
No history of congestive heart failure
No history of encephalitis or encephalopathy of any cause
No diverticulitis, gastrointestinal bleeding, or peptic ulcer within the past 3 months
No known AIDS or HIV-1 associated complex
No known history of immune or immunodeficiency disorders
No unstable or pre-existing major medical conditions except for cancer-related abnormalities

No other prior malignancy except for any of the following:

Adequately treated basal cell or squamous cell skin cancer
In situ cervical cancer
Adequately treated stage I or II cancer currently in complete remission
Any other cancer from which the patient been disease-free for 5 years
Concurrent chronic therapeutic doses of low molecular weight heparin allowed
At least 21 days since prior and no concurrent radiotherapy and recovered
At least 28 days since prior and no concurrent surgery (e.g., thoracic or other major surgeries) and recovered
No prior bevacizumab or other anti-angiogenic therapies including, but not limited to, small molecule tyrosine kinase inhibitors

No concurrent enzyme-inducing anticonvulsant drugs

Non-enzyme-inducing anticonvulsant drugs (e.g., Keppra) allowed
Concurrent chronic oral anticoagulation therapy allowed provided INR is maintained in the therapeutic range (INR 2-3)