Randomized Double-Blind Placebo Controlled Phase II Trial Evaluating Erlotinib in Non-Smoking Patients With (Bevacizumab-Eligible and Ineligible) Advanced Non-Small Cell Lung Cancer (NSCLC)

Inclusion Criteria:

- Histologically or cytologically confirmed non-small cell lung cancer, meeting one of
the following criteria:

- Stage IIIB disease with pleural or pericardial effusion or multifocal pleural
involvement

- Stage IV disease

- Recurrent disease after prior curative resection or definitive radiotherapy

- Non-squamous cell histology (for patients planning to receive bevacizumab)

- Has smoked ≤ 100 cigarettes in a lifetime

- Measurable disease as defined by RECIST criteria

- No history of untreated brain metastases

- ECOG performance status 0-1

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin ≤ 1.5 mg/dL

- SGOT and SGPT ≤ 3 times upper limit of normal

- Creatinine ≤ 2.0 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No clinically significant ongoing or active infection, symptomatic congestive heart
failure, unstable angina pectoris, symptomatic or uncontrolled cardiac arrhythmia, or
psychiatric illness/social situation that would limit compliance with study
requirements

- No other active, invasive malignancies requiring therapy

- Patients planning to receive bevacizumab must meet the following additional criteria:

- INR ≤ 3 within the past 4 weeks

- Urine protein ≤ 1+ by urine dipstick within the past 4 weeks OR urine
protein:creatinine ratio < 1.0

- No antecedent hemoptysis

- No history of thrombotic or hemorrhagic disorders

- History of hypertension allowed provided it is well controlled (i.e., BP ≤
150/90 mm Hg) and patient has been on a stable regimen of antihypertensive
therapy within the past 4 weeks

- History of myocardial infarction or other evidence of arterial thrombotic
disease (angina) allowed provided there is no evidence of active disease for ≥ 6
months

- No serious non-healing wound, ulcer, or bone fracture within the past 4 weeks

- No abdominal fistula, gastrointestinal perforation,or intra-abdominal abscess
within the past 6 months

- No significant vascular disease (e.g., aortic aneurysm,requires surgical repair,
or recent peripheral arterial thrombosis) within the past 6 months

- No clinically significant cardiovascular disease, including any of the
following:

- Cerebrovascular accident within the past 6 months

- New York Heart Association class II-IV heart failure

- Serious and inadequately controlled cardiac arrhythmia

- Clinically significant peripheral vascular disease (symptomatic with
intermittent claudications or < 6 months since bypass surgery)

- No prior chemotherapy for lung cancer

- More than 3 years since prior chemotherapy for an unrelated condition

- At least 2 weeks since prior radiotherapy and recovered (alopecia and grade 1
neuropathy allowed)

- No prior irradiation to the only site of measurable disease, unless that site has had
subsequent evidence of pathology or radiologic progression

- More than 28 days since prior major surgical procedure (for patients planning to
receive bevacizumab)

- Concurrent stable doses of therapeutic anticoagulation or prophylactic
anticoagulation for venous access devices allowed (for patients planning to receive
bevacizumab)