S0709: Erlotinib With or Without Carboplatin and Paclitaxel in Stage IIIB or Stage IV Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

- To select a regimen (erlotinib hydrochloride with or without carboplatin and paclitaxel)
for further testing against standard treatment, based on median progression-free
survival for ≥ 3 months, in patients with stage IIIB or IV non-small cell lung cancer
with a Zubrod performance status of 2.

Secondary

- To assess the feasibility of selecting patients for a trial based on central EGFR
testing of serum in a cooperative group setting.

- To evaluate the objective tumor response rates (confirmed and unconfirmed, complete and
partial response), in a subset of patients with measurable disease.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral erlotinib hydrochloride once daily on days 1-21. Courses
repeat every 21 days in the absence of disease progression or unacceptable toxicity.

- Arm II: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes
on day 1 and oral erlotinib hydrochloride once daily on days 2-16. Treatment repeats
every 21 days for 4 courses. Beginning in course 5 and for all subsequent courses,
patients receive oral erlotinib hydrochloride alone on days 1-21. Courses with erlotinib
hydrochloride repeat every 21 days in the absence of disease progression or unacceptable
toxicity.

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

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC),
including any of the following subtypes:

- Adenocarcinoma

- Large cell carcinoma

- Squamous cell carcinoma

- Newly diagnosed primary disease OR recurrent disease after prior surgery and/or
radiotherapy, meeting 1 of the following staging criteria:

- Selected stage IIIB disease (T4 [secondary to malignant pleural effusion only],
any N, M0)

- Stage IV disease (any T, any N, M1 [distant metastases present])

- Measurable or nonmeasurable disease by CT scan, MRI, x-ray, physical exam, or nuclear
scan

- The CT scan from a combined PET/CT scan may only be used to document
nonmeasurable disease

- Pleural effusions, ascites, and laboratory parameters are not acceptable as the
only evidence of disease

- Shows evidence of EGFR tyrosine kinase inhibitor therapy benefit (i.e., "proteomics
positive") prior to study registration

- No untreated brain metastases

- Patients with treated brain metastases are allowed provided metastases have
remained controlled for at least two weeks following treatment, AND patient has
no residual neurological dysfunction off corticosteroids

- Patients with neurologic abnormalities on physical examination or symptoms must
have a negative pretreatment CT or MRI scan of the brain 28 days prior to
registration

PATIENT CHARACTERISTICS:

- Zubrod performance status 2

- ANC ≥ 1,500/mm³

- Platelet count ≥ 1,000/mm³

- Serum bilirubin normal

- SGOT or SGPT normal

- Serum creatinine ≤ 2 times upper limit of normal OR creatinine clearance ≥ 50 mL/min

- Willing to provide prior smoking history as requested on the prestudy form

- No gastrointestinal (GI) tract disease resulting in an inability to take enteral
medication

- No malabsorption syndrome or requirement for IV alimentation

- No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)

- No significant history of cardiac disease, including any of the following:

- Uncontrolled high blood pressure

- Unstable angina

- Congestive heart failure

- Myocardial infarction within the past 6 months

- Cardiac ventricular arrhythmia requiring medication

- No other prior malignancy except adequately treated basal cell or squamous cell skin
cancer, in situ cervical cancer, adequately treated stage I or II cancer from which
the patient is currently in complete remission, or any other cancer from which the
patient has been disease-free for 5 years

- Not pregnant or nursing

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 3 weeks since prior radiotherapy or surgery (thoracic or other major surgery)
and recovered

- At least 1 year since prior adjuvant chemotherapy

- No prior systemic hormonal therapy, chemotherapy, or biological therapy for advanced
NSCLC

- No prior EGFR inhibitors

- No prior surgical procedures affecting absorption

- No concurrent major surgery