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

A Phase II Selection Design of Pharmacodynamic Separation of Carboplatin/Paclitaxel/OSI-774 (Erlotinib; NSC-718781) or OSI-774 Alone in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients With Performance Status 2 (PS-2)

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving erlotinib together with carboplatin and paclitaxel may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well erlotinib works when given alone or together with carboplatin and paclitaxel in treating patients with 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