Study of Oral Topotecan With Bevacizumab for Recurrent Small Cell Lung Cancer

An Open-label, Multicenter, Non-comparative, Phase II Study of Oral Topotecan in Combination With Bevacizumab for Second-line Treatment in Subjects With Relapsed Small-cell Lung Cancer (SCLC)

Combination of Hycamtin (topotecan) and Avastin (bevacizumab) could allow killing of both endothelial and neoplastic cells. We postulate that addition of bevacizumab to topotecan will increase delivery of topotecan to tumor cells and may enhance activity of topotecan in patients with previously treated small cell lung cancer and improve progression free survival.

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of SCLC.
• First recurrence of SCLC after therapy with one prior chemotherapy regimen at initial diagnosis.
• Relapsed SCLC of any duration (both sensitive and resistant relapse).
• ECOG performance status of </= 2.
• Adequate bone marrow reserve, hepatic, renal, and cardiovascular function.
• No prior therapy with bevacizumab or any other VEGF inhibitor or topotecan

Exclusion Criteria:

• Uncontrolled emesis, regardless of etiology.
• Active uncontrolled infection.
• GI conditions or drugs that could impact absorption of oral topotecan.
• Known hypersensitivity to any component of topotecan capsule or compounds chemically related to topotecan.
• Uncontrolled hypertension with BP>150/100.
• Prior h/o hypertensive crisis or encephalopathy.
• NYHA Grade II or greater congestive heart failure.
• H/O myocardial infarction within 6 months.
• H/O stroke or TIA within 6 months.
• H/O thrombotic or hemorrhagic disorders.
• Clinically significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days.
• Anticipation of need for major surgical procedure during the study.
• Minor surgical procedures within 7 days prior to treatment start (placement of vascular access devices is permitted).
• H/O abdominal fistula, GI perforation, or intra-abdominal abscess within prior 6 months. Serious, non-healing wound, active ulcer, or untreated bone fracture. - H/O hemoptysis within prior 1 month.
• Concurrent radiotherapy.
• H/O whole lung radiation within 90 days prior to start of treatment.
• Presence or h/o central nervous system or brain metastases.
• H/o another malignancy other than SCLC.
• Concurrent chemotherapy, immunotherapy, or investigational therapy for the treatment of small cell lung cancer.