A Two-Stage Phase 1 Dose Escalation Pharmacokinetic Study of Tarceva® (Erlotinib) in Patients With Stage IIIB/IV Non-small Cell Lung Cancer Who Continue To Smoke After Failure of One or Two Prior Chemotherapy Regimens

Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of stage IIIB/IV NSCLC;

- Must have received 1 or 2 prior chemotherapy regimens for advanced NSCLC and now have
progressive disease;

- Must have recovered from any treatment-related toxicities prior to registration,
except for alopecia, grade 1 fatigue, or grade 1 neurotoxicity;

- A current cigarette smoker (minimum of 10 cigarettes per day for >= 1 year and have a
positive test for cotinine) despite advice and support to quit;

- Age >= 18 years;

- ECOG PS 0-1 and predicted life expectancy >= 12 weeks;

- Previous surgery is permitted provided that wound healing has occurred prior to
registration;

- Adequate hematopoietic, hepatic and renal function defined as follows: ANC >= 1.5 x
10^9/L, platelets >= 100 x 10^9/L, bilirubin <= 1.5 x ULN, ALT <= 2.5 x ULN (or 5 x
ULN in case of liver metastases), creatinine <= 1.5 x ULN;

- No prior treatment with Tarceva or gefitinib (or other drug with significant activity
against EGFR (eg, cetuximab and/or ZD6474));

- Patients with reproductive potential must practice effective contraceptive measures
throughout the study. Women of child-bearing potential must provide a negative
pregnancy test within 14 days prior to registration;

- Accessible for repeat dosing and follow-up.

Exclusion Criteria:

- Any concurrent anticancer cytostatic or cytotoxic chemotherapy;

- Concomitant CYP3A4 or CYP1A2 inducers/inhibitors (or during 14 days prior to study)
with the exception of tobacco;

- Other active malignancies, unless disease-free and without cancer-specific therapy
for at least the last 5 years. Basal or squamous cell skin cancers are not excluded;

- Significant history of cardiac disease unless the disease is well-controlled;

- Active or uncontrolled infections or serious illnesses or medical conditions that
could interfere with the patient's ongoing participation in the study;

- History of any psychiatric condition that might impair the patient's ability to
understand or comply with the requirements; of the study or to provide informed
consent.

- Gastrointestinal abnormalities, including inability to take oral medication,
requirement for IV alimentation, active peptic ulcer or prior surgical procedures
affecting absorption;

- Clinically significant ophthalmologic abnormalities;

- Pregnant or breast-feeding females. Males or females not practicing effective birth
control;

- Symptomatic brain metastases which are not stable, require steroids, or that have
required radiation within the last 28 days;

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to the study drug;