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