Sorafenib in Treating Patients With Refractory Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Sorafenib; Placebo
Intervention description: Step 1 (induction): Sorafenib was giventwice daily for two cycles to all patients. Patients with progression (PD) discontinued treatment. Those who responded after two cycles continued treatment up to 1 year or until PD. With response after 1 year, patients were given the option to continue treatment until PD. Patients who were stable after the end of induction were then randomized onto Step 2 to either continue sorafenib or receive placebo.
Step 2 (randomization): Patients with stable disease after induction will be randomized in a double-blinded manner to placebo or sorafenib. If a patient has progressed, the arm will be unblinded. Patients on placebo with PD can then crossover to receive sorafenib; patients with PD on the sorafenib arm will be removed from the study.
Step 3 (crossover): If patients on placebo progressed within 1 year from randomization, they crossed over to the treatment arm and receive sorafenib for up to 1 year or until PD, unacceptable toxicity, or death.; Patients randomized to the placebo arm in step 2 continued receiving placebo until disease progression or one year from randomization. Placebo was given orally twice a day (BID).
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 342.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; sorafenib

Summary:

      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      withdrawn.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.
    

Eligibility criteria:

        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