S0802 - Topotecan With or Without Aflibercept in Treating Patients With Extensive-Stage Small Cell Lung Cancer
Condition: Extensive Stage Small Cell Lung Cancer; Recurrent Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: ziv-aflibercept; topotecan hydrochloride
Intervention description: Given IV; Given IV
Intervention MeSH terms: Aflibercept; Topotecan; Endothelial Growth Factors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 189.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial is studying topotecan to see how well it works when given with
      or without aflibercept in treating patients with extensive-stage small cell lung cancer.
      Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of
      tumor cells, either by killing the cells or by stopping them from dividing. Combinations of
      biological substances in aflibercept may be able to carry tumor-killing substances directly
      to small cell lung cancer cells. Aflibercept may also stop the growth of small cell lung
      cancer by blocking blood flow to the tumor. It is not yet known whether topotecan is more
      effective with or without aflibercept in treating patients with small cell lung cancer.
    

Eligibility criteria:

        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)