Combination Chemotherapy, Bev, RT, and Erlotinib in Treating Patients With Stage III Non-Small Cell Lung Cancer

OBJECTIVES: Primary * Determine the maximum tolerated dose of bevacizumab and erlotinib hydrochloride when given together with carboplatin, paclitaxel, and thoracic conformal radiotherapy in patients with stage IIIA or IIIB non-small cell lung cancer. (Phase I \[closed to accrual as of 1/3/2008\]) * Determine the safety and toxicity profile of this regimen in these patients. (Phase I \[closed to accrual as of 1/3/2008\]) * Determine the progression-free survival of patients treated with induction therapy comprising carboplatin, paclitaxel, and bevacizumab followed by chemoradiotherapy comprising thoracic conformal radiotherapy, carboplatin, paclitaxel, bevacizumab, and erlotinib hydrochloride and consolidation therapy comprising bevacizumab and erlotinib hydrochloride. (Phase II) * Determine the overall toxicity profile of this regimen in these patients. (Phase II) Secondary * Determine the response rate in patients treated with induction therapy comprising carboplatin, paclitaxel, and bevacizumab. (Phase I\[closed to accrual as of 1/3/2008\] and II) * Determine the toxicity profile of induction therapy in these patients. (Phase I \[closed to accrual as of 1/3/2008\] and II) * Determine the overall response rate and survival profile in patients treated with this regimen. (Phase I \[closed to accrual as of 1/3/2008\] and II) * Determine the feasibility and tolerability of administering consolidation therapy comprising erlotinib hydrochloride and bevacizumab after treatment with combined modality therapy (induction therapy and chemoradiotherapy) in these patients. (Phase I \[closed to accrual as of 1/3/2008\] and II) * Collect tumor and blood samples from these patients for future analysis of correlation between molecular markers and clinical benefit. (Phase I \[closed to accrual as of 1/3/2008\] and II) OUTLINE: This is a nonrandomized, open-label, controlled, phase I (closed to accrual as of 1/3/2008), dose-escalation study of bevacizumab and erlotinib hydrochloride, followed by a phase II study. * Phase I (closed to accrual as of 1/3/2008): * Induction therapy: Patients receive paclitaxel IV over 3 hours, carboplatin IV over 15-30 minutes, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 2 courses. Patients with stable or responding disease proceed to chemoradiotherapy. * Chemoradiotherapy: Patients receive chemoradiotherapy according to their assigned dose cohort: * Cohort 1: Patients undergo thoracic conformal radiotherapy (TCRT) on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47. Patients also receive carboplatin IV and paclitaxel IV on days 1, 8, 15, 22, 29, 36, and 43 and bevacizumab IV over 30-90 minutes on days 1, 15, 29, and 43. * Cohort 2: Patients undergo TCRT and receive carboplatin, paclitaxel, and bevacizumab as in cohort 1. Patients also receive oral erlotinib hydrochloride on days 2-5, 9-12, 16-19, 23-26, 30-33, 37-40, and 44-47. * Cohort 3: Patients undergo TCRT and receive carboplatin, paclitaxel, and bevacizumab as in cohort 1. Patients also receive higher doses of oral erlotinib hydrochloride on days 2-5, 9-12, 16-19, 23-26, 30-33, 37-40, and 44-47. Cohorts of 5 patients receive chemoradiotherapy as described above until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 (with grade 4 toxicity) or 3 (with grade 3 toxicity) of 5 patients experience dose-limiting toxicity. Three to 6 weeks after completion of chemoradiotherapy, patients proceed to consolidation therapy. * Consolidation therapy: Patients receive bevacizumab IV on day 1 and oral erlotinib hydrochloride on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. * Phase II: * Induction therapy: Patients receive induction therapy as in phase I (closed to accrual as of 1/3/2008). * Chemoradiotherapy: Patients undergo TCRT and receive carboplatin and paclitaxel as in phase I (closed to accrual as of 1/3/2008). Patients also receive bevacizumab and erlotinib hydrochloride as in phase I (closed to accrual as of 1/3/2008) at the MTD/drug combination determined in phase I (closed to accrual as of 1/3/2008). * Consolidation therapy: Patients receive consolidation therapy as in phase I (closed to accrual as of 1/3/2008). Tumor tissue and peripheral blood is collected at baseline for future correlative and biomarker studies. After completion of study therapy, patients are followed every 2 months for 2 years, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.