Erlotinib + Bevacizumab for PS 2 Chemotherapy Naïve Non-Small Cell Lung Cancer

OUTLINE: This is a multi-center study.

• Bevacizumab 15 mg/kg IV on day 1
• Erlotinib 150 mg po qd days 1-21
• Disease Assessment during even numbered cycles

If no progressive disease observed, continue (combination or single agent- see below) until unacceptable toxicity or progressive disease.

If progressive disease observed, treatment will be discontinued.

• Cycles will be repeated every 21 days up to a total of 6 cycles.
• Patients with non-progression after 6 cycles may stay on therapy (single agent erlotinib or the combination) until progressive disease or intolerable toxicity (at the physician discretion).
• Patients who require discontinuation of bevacizumab may receive at investigator's discretion erlotinib alone on study until progression.
• Patients who require discontinuation of erlotinib may receive at investigator's discretion bevacizumab alone until progression.

ECOG Performance Status 2

Hematopoietic:

• Absolute neutrophil count (ANC) > 1,000 mm3
• Platelet count > 100,000 mm3
• Hemoglobin > 8 g/dl

Hepatic:

• Bilirubin < 2 X upper limit of normal.
• Aspartate aminotransferase (AST, SGOT) < 2.5 X upper limit of normal or 5 X if liver involvement.

Renal:

• Urine protein:creatinine ratio 1.0 at screening

Cardiovascular:

• Blood pressure of < 150/100 mmHg.
• No history of unstable angina.
• No history of New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• No history of myocardial infarction within 6 months prior to registration for protocol therapy.
• No history of stroke within 6 months prior to registration for protocol therapy.
• No clinically significant peripheral vascular disease.

Inclusion criteria

• Histological proof of non-small cell lung cancer meeting one of the following criteria:

• stage III b with a pleural effusion
• stage IV
• Histology must not be squamous cell.
• No prior chemotherapy or hormonal therapy.
• Prior radiation therapy must be completed at least 21 days prior to being registered for protocol therapy.
• No prior use of an epidermal growth factor receptor (EGFR) inhibitor or antiangiogenic agent.
• No treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
• Measurable disease according to RECIST and obtained by imaging within 28 days prior to being registered for protocol therapy.
• ECOG Performance Status of 2 in the opinion of the treating investigator.
• Age > 18 years at the time of consent.
• Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) while on treatment and for a 6 week period thereafter.
• Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy. Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
• Females must not be breastfeeding.
• Able to comply with study and/or follow-up procedures.

Exclusion criteria

• Evidence of bleeding diathesis or coagulopathy.
• Evidence of central nervous system involvement or brain metastases confirmed by head CT or brain MRI within 28 days prior to being registered for protocol therapy.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration for protocol therapy.
• Anticipation of need for major surgical procedure during the course of the study.
• Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to registration for protocol therapy.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to registration for protocol therapy.
• Serious, non-healing wound, ulcer, or bone fracture.
• History of hemoptysis.
• Clinically significant infections as judged by the treating investigator.
• Other active malignancy