Proteomic Profiling in Predicting Response in Patients Receiving Erlotinib for Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

RATIONALE: Studying samples of tumor tissue, blood, and urine in the laboratory from patients receiving erlotinib may help doctors predict how patients will respond to treatment.

PURPOSE: The phase II trial is studying proteomic profiling to see how well it predicts response in patients receiving erlotinib for stage IIIB, stage IV, or recurrent non-small cell lung cancer.

OBJECTIVES:

Primary

* To define a pre-treatment tumor proteomic profile that predicts response, stable disease, or progressive disease in patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer treated with erlotinib hydrochloride.

Secondary

* To test and refine a pre-treatment serum proteomic expression pattern that predicts response to erlotinib hydrochloride and/or carboplatin and paclitaxel after failing treatment with erlotinib hydrochloride.
* To test and refine tumor proteomic profiles that predict response to carboplatin and paclitaxel after failing treatment with erlotinib hydrochloride.
* To analyze individual and pattern(s) of erlotinib hydrochloride-induced genomic and proteomic biomarker changes in relation to response or non-response to treatment.
* To correlate the efficacy and toxicity of erlotinib hydrochloride with expression of EGFR, EGFR pathway, ErbB family, and other related biomarkers.
* To determine a set of biomarkers to be evaluated in tumor tissue or surrogate tissues prior to treatment with erlotinib hydrochloride to enable patient selection for therapy.
* To estimate response rate and progression-free and overall survival of patients treated with erlotinib hydrochloride as initial therapy.
* To characterize the safety profile of erlotinib hydrochloride in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride once daily until disease progression.

At the time of disease progression, patients receive standard chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 15-30 minutes on day 1. Patients with non-squamous cell non-small cell lung cancer also receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses.

Tumor tissue, plasma, serum, and urine samples are collected at baseline for proteomics analysis.

After the completion of study treatment, patients are followed every 8 weeks.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed non-small cell lung cancer (NSCLC), meeting 1 of the following criteria:

  * Stage IIIB (with pleural effusion) or stage IV disease
  * Recurrent disease after prior surgery
* Measurable or evaluable disease is desirable but not required
* No untreated symptomatic brain metastases

  * Patients who are neurologically unstable despite radiotherapy for the brain metastases are not eligible
  * No requirement for steroids to control neurological symptoms

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* ANC ≥ 1,500/mm³
* Hemoglobin ≥ 9 g/dL
* Platelet count ≥ 100,000/mm³
* Creatinine ≤ 2.0 mg/dL
* Total bilirubin ≤ 1.5 mg/dL
* Normal hemostasis by history
* PT/PTT within 0.5 seconds of normal range
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Willing to undergo biopsy procedures
* No known severe hypersensitivity to erlotinib hydrochloride or any of the excipients of this product
* No other concurrent malignancies or malignancies diagnosed within the past 5 years, except basal cell carcinoma or cervical cancer in situ
* No significant cardiac disease, including any of the following:

  * NYHA class III or IV heart disease
  * Uncontrolled dysrhythmia
  * Myocardial infarction within the past 6 months
* No evidence of clinically active interstitial lung disease

  * Chronic stable radiographic changes that are asymptomatic allowed
* No evidence of any other severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
* No evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial
* No uncontrolled hypertension

  * Blood pressure must be ≤ 150/90 mmHg on a stable antihypertensive regimen

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 6 months since prior adjuvant chemotherapy
* No unresolved chronic toxicity \> CTC grade 2 from prior anticancer therapy (except alopecia)
* More than 30 days since prior non-approved or investigational drugs
* No prior chemotherapy for advanced NSCLC
* No concurrent phenytoin, carbamazepine, rifampin, barbiturates, or St. John's wort
* No concurrent administration of other drugs known to inhibit EGFR
* No other concurrent anti-neoplastic or anti-tumor agents, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy
* No other concurrent investigational agents
* Concurrent cardioprotective doses of aspirin, as recommended by the physician, for cardiovascular disease allowed