Phase I/II Study of Erlotinib (TARCEVA) and Cetuximab (ERBITUX) in Advanced Solid Tumors, With Emphasis on Non Small Cell Lung Cancer (NSCLC)

OBJECTIVES: Primary * Determine the safety and feasibility of erlotinib hydrochloride and cetuximab in patients with advanced solid tumors. (Phase I) * Determine the efficacy of this regimen, in terms of objective tumor response rate, in patients with advanced non-small cell lung cancer (NSCLC) pre-treated with platinum. (Phase II) Secondary * Determine the maximum tolerated dose of this regimen in these patients. (Phase I) * Determine the efficacy of this regimen, in terms of response rate, in these patients. (Phase I) * Determine the progression-free and overall survival of patients treated with this regimen. (Phase II) * Determine the frequency and severity of toxicities of this regimen in these patients. (Phase II) * Determine epidermal growth factor receptor (EGFR) and K-RAS mutation status. (Phase II) * Evaluate EGFR protein expression and protein expression of downstream markers (e.g., pMAPK, pAKT, p27, and Ki-67). (Phase II) * Evaluate the levels of marker proteins (e.g., pMAPK, pAKT, p27, and Ki-67) in buccal cells. (Phase II) * Determine gene copy number by EGFR fluorescent in situ hybridization (FISH). (Phase II) * Identify EGFR polymorphisms by analysis of genomic DNA from peripheral blood mononuclear cells. (Phase II) * Determine if the continued presence or absence of mutant K-RAS tumor DNA correlates with response and/or outcome. (Phase II) OUTLINE: This is a phase I, dose-escalation study followed by an open-label, phase II study. * Phase I: Patients receive oral erlotinib hydrochloride once daily on days 1-28 and cetuximab IV over 1-2 hours on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib hydrochloride and cetuximab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which ≥ 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. * Phase II: Patients receive erlotinib hydrochloride and cetuximab at the MTD determined in phase I. Blood and buccal samples are acquired from patients at baseline and prior to courses 2 and 3. Samples are examined by fluorescent in situ hybridization (FISH), immunohistochemistry, polymorphism analysis, and protein expression assays to assess molecular markers (epidermal growth factor receptor, K-RAS, pMAPK, pAKT, p27 and Ki-67) for biologic effects and predictive response. After completion of phase I treatment, patients are followed for 30 days or until all toxicities resolve. After completion of phase II treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study