Sorafenib in Treating Patients With Refractory Non-Small Cell Lung Cancer

OBJECTIVES:

- To determine the percent of patients maintaining stable disease or objective response
two months after randomization with continued sorafenib treatment, compared to patients
switched to placebo.

- To determine progression-free survival, overall survival, and response rate.

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.

- Arm I: Patients receive oral sorafenib twice daily for up to 1 year in the absence
of disease progression or unacceptable toxicity.

- Arm II: Patients receive oral placebo twice daily for up to 1 year in the absence
of disease progression or unacceptable toxicity. Patients who develop disease
progression within 1 year after randomization cross over to arm I.

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:

- Histologically or cytologically confirmed advanced non-small cell lung cancer (NSCLC)

- Disease must have progressed after at least 2 prior chemotherapy regimens for NSCLC

- Patients must have measurable or nonmeasurable disease

- Absolute neutrophil count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- AST and ALT no greater than 3 times ULN (5 times ULN in patients with liver disease)

- Creatinine less than 1.5 times ULN or calculated creatinine clearance greater than 50
mL/min

- More than 3 weeks since prior chemotherapy, radiotherapy, immunotherapy or other
investigational drug use

- Recovered from all prior therapy

- Fertile patients must use effective contraception

- Age >= 18

- ECOG performance status of 0-1

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:

- Ketoconazole

- Itraconazole

- Quinidine

- Digoxin

- Cyclosporine

- Ritonavir

- Grapefruit products

- Carbamazepine

- Phenytoin

- Phenobarbital

- Pregnant or nursing

- Clinically serious active infection

- Medical conditions, substance abuse or psychological/social situation that would
preclude study participation