A Double Blind Phase II Study of BAY 43-9006 in Patients With Non-Small Cell Lung Cancer Who Have Failed at Least Two Prior Chemotherapy Regimens
A Double Blind Phase II Study of BAY 43-9006 in Patients With Non-Small Cell Lung Cancer Who Have Failed at Least Two Prior Chemotherapy Regimens
RATIONALE: Preclinical studies indicate that sorafenib is a potent inhibitor of Raf kinase in vitro and in vivo, with significant dose-dependent, anti-tumor activity in four different human tumor types including colon, pancreatic, lung, and ovarian. This activity was cytostatic in nature and was maintained if dosing was continued. That is, tumor growth is suspended while the drug is administered but returns to baseline rates when the agent is withdrawn. Therefore, the optimal schedule will be an uninterrupted one. To assess the activity of sorafenib in a timely manner and with a meaningful interpretation, a randomized discontinuation design was adopted in the present trial, conducted in a population who were potentially sensitive to sorafenib.
PURPOSE: This randomized phase II trial is studying sorafenib to see how well it works compared to placebo in treating patients with refractory non-small cell lung cancer.
OBJECTIVES:
OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to number of prior chemotherapy regimens (2 vs more than 2) and prior epidermal growth factor receptor inhibitor treatment (yes vs no).
Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression.
Randomization: Patients are randomized to 1 of 2 treatment arms.
Patients are followed every 3 months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 311 patients will be accrued for this study within approximately 3 years.
Inclusion Criteria:
Exclusion Criteria:
Prior primary or metastatic brain or meningeal tumors unless clinically and radiographically stable and off therapy for at least 2 months
Active second malignancy
Clinically evident congestive heart failure, serious cardiac arrhythmias, or symptoms of coronary heart disease
Prior radiotherapy to the only site of measurable or evaluable disease unless there is evidence of disease progression in that site
Prior exposure to a ras pathway inhibitor (e.g., farnesyl transferase inhibitor)
Concurrent medications known to be metabolized by the liver with a narrow therapeutic index, including the following:
Pregnant or nursing
Clinically serious active infection
Medical conditions, substance abuse or psychological/social situation that would preclude study participation
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