Phase I Study of Weekly Topotecan in Combination With Sorafenib in Treatment of Relapsed Small Cell Lung Cancer

• Status: Completed
• Trial end date: 2010-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to determine the maximum tolerated dose of sorafenib up to the full active dose when combined with standard weekly dosing of topotecan in patients with recurrent small cell lung cancer and to characterize the toxicities associated with the combination of topotecan and sorafenib in this patient population

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: HealthPartners Institute
• Treatments: Niacinamide; Sorafenib; Topotecan

Criteria

Inclusion Criteria:

• Patients must have histologically proven small cell carcinoma of bronchogenic origin.

• Must have received one course of systemic chemotherapy which included cisplatin or carboplatin. Chemotherapy administered during radiation is allowable.

• Must have radiographically documented disease recurrence or progression by CT scan or bone scan. CNS only recurrence is not sufficient. Measurable disease per RECIST criteria is not required.

• ECOG Performance status of 0 to 2

• Adequate organ function within 14 days of study enrollment as defined by the following:

• Absolute neutrophil count ≥ 1500/mm3

• Platelet count ≥ 100,000/mm3

• Hemoglobin ≥ 9 gm/dL

• Creatinine ≤ 1.5 mg/dL

• Bilirubin < 1.5 times upper limit of normal (x UNL)

• Alkaline phosphatase, aspartate transaminase and alanine transaminase < 3 x ULN (may be <5 x ULN if hepatic metastases)

• Women of childbearing potential and sexually active males must use an effective method of contraception during the study and for 3 months after the last dose of study drug.

• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.

• Treated brain metastases that are stable for a minimum of 4 weeks following surgery or radiation and off therapeutic glucocorticoids are allowed.

• INR<1.5 or a PT/PTT within normal limits. Patients receiving anti- coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.

• Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.

Exclusion Criteria:

• Pregnant or breast feeding.

• Myocardial infarction or cerebrovascular accident within 6 months.

• Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg despite optimal medical management.

• History of other active invasive malignancy (except for basal cell or squamous cell skin cancer) within 12 months.

• Major surgery within 4 weeks.

• Chemotherapy within 4 weeks.

• Cardiac disease: Congestive heart failure > NYHA Class II, unstable or new-onset angina within prior 3 months.

• History of bleeding diathesis or coagulopathy.

• Active clinically serious infection > CTCAE Grade 2.

• Ventricular arrhythmias requiring anti-arrhythmic therapy.

• Serious non-healing wound, ulcer or fracture.

• Any hemorrhage or bleeding event > CTCAE Grade 3 within 4 weeks of study enrollment.

• Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug.

• Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.

• Known human immunodeficiency virus (HIV) or chronic hepatitis B or C infection.

• Any condition that impairs patient's ability to swallow whole pills.

• Any gastrointestinal malabsorption syndrome

• Use of St. John's wort or rifampin.