A Phase II Study of Erlotinib and Sorafenib in Patients With Locally Advanced and/or Metastatic (Stage IIIb or IV) Non Small Cell Lung Cancer Who Have Not Received Prior Chemotherapy
1. Histologically/cytologically advanced NSCLC stage IIIB or IV
2. No prior chemotherapy or therapy with systemic anti-tumor therapy (e.g., monoclonal
antibody therapy) or prior exposure to agents directed at the HER axis (e.g. EGFR TK
inhibitors, Herceptin). Prior surgery and/or localized irradiation is permitted
provided that the irradiated lesion is not the only measurable lesion.
3. Age > 18 years.
4. ECOG Performance Status of 0 or 1
5. Life expectancy of at least 12 weeks.
6. Subjects with at least one uni-dimensional(for RECIST) measurable lesion. Lesions
must be measured by CT-scan.
7. Adequate bone marrow, liver and renal function as assessed by the following
laboratory requirements to be conducted within 7 days prior to screening:
8. Hemoglobin > 9.0 g/dl
9. Absolute neutrophil count (ANC) >1,500/mm3
10. Platelet count > 100,000/μl
11. Total bilirubin < 1.5 times the upper limit of normal
12. ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients
with liver involvement of their cancer)
13. Alkaline phosphatase < 4 x ULN
14. PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically
anticoagulated with low molecular weight heparin will be allowed to participate
provided that no prior evidence of underlying abnormality in these parameters
15. Serum creatinine < 1.5 x upper limit of normal.
16. Written informed consent.
Excluded medical conditions:
1. History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI
more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring
anti-arrhythmic therapy( beta blockers or digoxin are permitted) or uncontrolled
2. History of HIV infection or chronic hepatitis B or C.
3. Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
4. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 1 months
from definitive radiotherapy and off steroids):
5. Patients with seizure disorder requiring medication (such as steroids or
6. History of organ allograft.
7. Patients with evidence or history of bleeding diathesis
8. Patients undergoing renal dialysis
9. Previous or concurrent cancer that is distinct in primary site or histology from the
cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal
cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively
treated > 3 years prior to study entry.
Excluded therapies and medications, previous and concomitant:
1. Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study
2. Radiotherapy during study or within 3 weeks of start of study drug. (Palliative
radiotherapy will be allowed). Major surgery within 3 weeks of start of study
3. Autologous bone marrow transplant or stem cell rescue within 4 months of study
4. Use of biologic response modifiers, such as G-CSF, within 3 week of study entry.
[G-CSF and other hematopoietic growth factors may be used in the management of acute
toxicity such as febrile neutropenia when clinically indicated or at the discretion
of the investigator, however they may not be substituted for a required dose
reduction.] [Patients taking chronic erythropoietin are permitted provided no dose
adjustment is undertaken within 2 months prior to the study or during the study]
5. Investigational drug therapy outside of this trial during or within 4 weeks of study
6. Prior exposure to the study drugs.
7. Pregnant or breast-feeding patients. Women of childbearing potential must have a
negative pregnancy test performed within 7 days of the start of treatment. Both men
and women enrolled in this trial must use adequate barrier birth control measures
during the course of the trial and two weeks after the completion of trial.
8. Substance abuse, medical, psychological or social conditions that may interfere with
the patient's participation in the study or evaluation of the study results
9. Any condition that is unstable or could jeopardize the safety of the patient and
their compliance in the study
10. Patients unable to swallow oral medications.