Erlotinib and Standard Platinum-Based Chemotherapy for Newly Diagnosed, Advanced Non-Small Cell Carcinoma of the Lung

To compare the activities (the progression-free survival, the incidence and severity of
toxicities, and reversibility of toxicities) of erlotinib to that of platinum-based therapy
in NSCLC. A sequential therapy design has been chosen such that all patients will receive
any potential benefits of both platinum-based and erlotinib therapy, without compromising
survival by denying anyone potential therapy. With this design, progression-free survival
will be tracked by treatment received. However, data will be generated which will show the
safety and efficacy of erlotinib in the frontline setting (alone and with historical
comparison to platinum-based therapy), as well as the potential safety and activity of
platinum-based therapy in the "second-line" (post-erlotinib) setting. This should allow for
the demonstration of the relative median time to progression, objective response and
clinical benefit rates, overall survival, and safety and tolerability of erlotinib and
platinum-based therapy in both the frontline and second-line settings in NSCLC. Also, in
this fashion, the treatments serve as controls for each other, as well as being compared to
historical controls; in the first line treatment portion, the platinum-based regimens serve
as the historical control, while in the second-line setting, erlotinib serves as the
historical control arm.

Inclusion Criteria:

- Prior chemotherapy will be allowed for other invasive malignancies, provided at least
five years has elapsed since the completion of therapy and enrollment on this
protocol. No prior chemotherapy for metastatic non-small cell lung cancer (NSCLC)
will be allowed. Prior adjuvant or neoadjuvant chemotherapy for NSCLC will be
allowed, provided at least six months have elapsed from the last dose of chemotherapy
to the documentation of relapsed disease.

Baseline laboratory values (bone marrow, renal, hepatic):

- Adequate bone marrow function:

- Absolute neutrophil count >1000/µL

- Platelet count >100'000/µL

- Renal function:

- Serum creatinine < 2.0 mg %

- Hepatic function:

- Bilirubin <1.5x normal

- Serum calcium < 12 mg/dl

Other Eligibility Criteria:

- Signed Informed Consent

- Eastern Cooperative Oncology Group (ECOG)/Zubrod/Southwest Oncology Group (SWOG)
Performance Status <2 (Karnofsky Performance Status > 70%)

- Life expectancy > 8 weeks

- Male or female' age >18 years

- Patients of childbearing potential must be using an effective means of contraception.

- Histologic diagnosis of NSCLC that is advanced and cannot be treated adequately by
radiotherapy or surgery; or metastatic disease

Exclusion Criteria:

- Prior therapy with an epidermal growth factor receptor inhibitor, including
erlotinib, gefitinib, and cetuximab, as well as any investigational HER-1 inhibiting
agent

- Pregnant or lactating females

- Myocardial infarction or ischemia within the 6 months before Cycle 0' Day 0

- Uncontrolled' clinically significant dysrhythmia

- History of prior malignancy within the prior five years, with the exception of
non-melanoma carcinomas of the skin, and carcinoma in situ of the cervix

- Prior radiotherapy to an indicator lesion unless there is objective evidence of tumor
growth in that lesion

- Uncontrolled metastatic disease of the central nervous system (previously treated,
stable disease is allowable on this protocol)

- Radiotherapy within the 2 weeks before Cycle 1' Day 1

- Surgery within the 2 weeks before Cycle 1' Day 1

- Any co morbid condition that' in the view of the attending physician' renders the
patient at high risk from treatment complications