Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer

PRIMARY OBJECTIVES:

I. To determine the distribution of progression-free survival (PFS) in patients with
previously untreated advanced adenocarcinoma of the lung who are never or light former
smokers treated with either OSI-774 (erlotinib) (erlotinib hydrochloride) alone (arm A) or in
combination with carboplatin/paclitaxel (arm B).

SECONDARY OBJECTIVES:

I. To determine the radiographic response rate in patients with previously untreated advanced
adenocarcinoma of the lung who are never or light former smokers treated with either OSI-774
(erlotinib) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

II. To determine the frequency of epidermal growth factor receptor (EGFR) and V-Ki-ras2
Kirsten rat sarcoma viral oncogene homolog (K-ras) mutations and anaplastic lymphoma kinase
(ALK) translocations in patients with previously untreated advanced adenocarcinoma of the
lung who are never or light former smokers.

III. To determine the response rate and time to progression in patients with and without EGFR
mutations treated with either OSI-774 (erlotinib) alone (arm A) or in combination with
carboplatin/paclitaxel (arm B).

IV. To determine the response rate and time to progression in patients with and without K-ras
mutations treated with either OSI-774 (erlotinib) alone (arm A) or in combination with
carboplatin/paclitaxel (arm B).

V. To determine the median and overall survival of patients with previously untreated
advanced adenocarcinoma of the lung who are never or light former smokers treated with either
OSI-774 (erlotinib) alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

VI. To estimate the response rate, progression-free, and overall survival of patients with
echinoderm microtubule associated protein like (EML)4-ALK translocation who received OSI-774
erlotinib alone (arm A) or in combination with carboplatin/paclitaxel (arm B).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-21.
Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive erlotinib hydrochloride as in Arm I. Patients also receive
paclitaxel intravenously (IV) over 1-3 hours and carboplatin IV over 15-30 minutes on day 1.
Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or
unacceptable toxicity. After completion of 6 cycles of treatment, patients may continue to
receive erlotinib hydrochloride alone as above.

After completion of study treatment, patients are followed at least every 3 months for 1 year
and then every 6 months for up to 2 years.

Inclusion Criteria:

- Histologic documentation of primary lung adenocarcinoma including any variant thereof
such as pure or mixed bronchioloalveolar carcinoma or adenosquamous cell carcinoma;
patients with non-small cell lung cancer (NSCLC) not otherwise specified (NOS) are not
eligible

- Pathology block or unstained slides from initial or subsequent diagnosis must be
available for sequencing of EGFR, K-ras, Erb-2 and B-raf; patients need to have
had at least a core biopsy; patients whose diagnosis was made through a fine
needle aspirate will not have sufficient material for mutational analysis and are
not eligible

- Select stage IIIB with cytologically documented malignant pleural or pericardial
effusion OR stage IV disease

- Patients must be chemotherapy naïve; they may not have received neo-adjuvant or
adjuvant chemotherapy

- No prior exposure to OSI-774 (erlotinib) or other treatments targeting the human
epidermal growth factor receptor (HER) family axis (e.g., trastuzumab, gefitinib,
cetuximab, lapatinib, etc.)

- No uncontrolled central nervous system metastases (i.e., any known central nervous
system [CNS] lesion which is radiographically unstable, symptomatic and/or requiring
corticosteroids); patients must be >= 3 weeks beyond completing cranial irradiation
and off corticosteroid therapy

- >= 3 weeks since prior radiation therapy

- >= 3 weeks since prior major surgery

- No treatment with an investigational agent currently or within the last 28 days

- Non-smoker or former light smoker; non-smoker is defined as a person who smoked =< 100
cigarettes in their lifetime while a former light smoker is a patient who smoked
between > 100 cigarettes AND =< 10 pack years AND quit >= 1 year ago; this must be
documented on the On-study Form (C-1405)

- Eastern Cooperative Oncology Group (ECOG) 0 or 1

- Non-pregnant and non-nursing

- No dysphagia or active gastrointestinal disease or disorder that alters
gastrointestinal motility or absorption; no lack of integrity of the gastrointestinal
tract (e.g., a significant surgical resection of the stomach or small bowel); patients
unable to swallow intact tablets must be able to swallow tablets dissolved in water

- Measurable disease is defined as at least one lesion that can be accurately measured
in at least one dimension (longest diameter to be recorded) as >= 20 mm with
conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan;
lesions that are considered non-measurable include the following:

- Bone lesions

- Leptomeningeal disease

- Ascites

- Pleural/pericardial effusion

- Lymphangitis cutis/pulmonis

- Abdominal masses that are not confirmed and followed by imaging techniques

- Cystic lesions

- Granulocyte >= 1,500/mcl

- Platelet count >= 100,000/mcl

- Hemoglobin >= 9.0 g/dL

- Total bilirubin =< upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =<
2.5 x ULN

- Creatinine =< 1.5 mg/dl