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

A Feasibility Study Investigating Translational Science in Chemotherapy-Naive Patients With Stage IIIb or IV Non-Small Cell Lung Cancer (NSCLC) Treated With the EGFR-TKI, Erlotinib

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.

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