Combination of Erlotinib and Bevacizumab as Second-line Treatment in Patients With Non-small Cell Lung Cancer

Combination of Erlotinib (Tarceva®) and Bevacizumab (Avastin®) as Second-line Treatment in Locally Advanced / Metastatic, Non-squamous, Non-small Cell Lung Cancer (NSCLC) Patients: A Phase II Study

The purpose of this study is to evaluate the efficacy and toxicity of combination of erlotinib and bevacizumab in patients with locally advanced or metastatic, non-squamous non-small cell lung cancer, who progressed after first line treatment. Pretreatment with one of the two agents would not excluded patients from the study, in order to evaluate whether the combination of the two biologic agents could reverse tumor resistance.

A randomized, placebo-controlled phase III trial of erlotinib versus placebo, demonstrated that therapy with this tyrosine kinase inhibitor (TKI) prolongs survival after first or second line therapy in patients with advanced NSCLC. Moreover, the addition of bevacizumab, a monoclonal antibody against Vascular Endothelial Growth Factor bevacizumab (VEGF), to systemic chemotherapy, improved both the response rates and the time to tumor progression in two trials. Early data from phase I/II trials examining the combination of these two biological agents in pre-treated patients with non-squamous NSCLC, showed no major pharmacokinetic interactions and promising clinical activity.

Inclusion Criteria:

• Histologically or cytologically confirmed, unresectable locally advanced (stage IIIB with pleural effusion) and/or metastatic (stage IV) NSCLC
• Progression to first-line therapy for advanced/metastatic NSCLC
• Bi-dimensionally measurable disease (not included in radiation field)
• ECOG performance status of 0-2
• Life expectancy of more than 6 months
• Adequate liver (serum bilirubin <1.5 times the upper normal limit, AST and ALT <2.5 times the upper normal limit in the absence of demonstrable liver metastases, or <5 times the upper normal limit in the presence of liver metastases,adequate renal function (serum creatinine <1.5 times the upper normal limit),and bone marrow (neutrophils ≥ 1.5x 109 /L, and platelets ≥ 100x 109 /L) function
• Signed informed consent

Exclusion Criteria:

• Central nervous system involvement (unless if the patient has being previously irradiated and is clinically stable)
• Presence of a centrally located mass or a tumor mass in close relation to large vessels or a mass with cavitation.
• Surgery or radiation therapy within the last 14 days from study entry
• Active infection
• History of life-threatening hemoptysis / hematemesis, history of thrombosis or use of anti-coagulation therapy
• History of significant cardiac disease (unstable angina, congestive heart failure, myocardial infarction, ventricular arrhythmias) or stroke within the previous 6 months or uncontrolled hypertension
• Patients on other experimental treatment protocols
• History of a second primary malignancy (other than basal-cell skin carcinoma or in situ carcinoma of the cervix)
• Psychiatric illness or social situation that would preclude study compliance
• Pregnant or lactating women