Patient case: 50-year-old male with non-small cell lung cancer; genetic feature: EGFR (T790M)

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

Summary: 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.

Detailed description: 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: 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

Relevance to patient case: possibly relevant