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
• Unspecified
• 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