proteomic profiling in predicting response in patients receiving erlotinib for stage iiib, stage iv, or recurrent non-small cell lung cancer

Conditions: 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.

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

Keywords: stage iiib non-small cell lung cancer stage iv non-small cell lung cancer recurrent non-small cell lung cancer squamous cell lung cancer adenosquamous cell lung cancer bronchoalveolar cell lung cancer large cell lung cancer adenocarcinoma of the lung