Given the single-agent activity of pemetrexed in the first and second-line treatment of metastatic NSCLC and the tolerability of pemetrexed in combination with radiation, we propose a study evaluating pemetrexed and radiation in patients with poor risk stage III NSCLC. The primary objective is to determine progression free survival in patients with poor risk stage III NSCLC treated with pemetrexed and concurrent definitive radiation. Secondary objectives are to determine the toxicities and overall survival of pemetrexed and concurrent definitive radiation in patients with poor risk stage III NSCLC.
Subjects must have histological or cytological proof of NSCLC, measurable or nonmeasurable disease per RECIST, unresectable Stage IIIA or IIIB disease, and at least one of the following: ECOG PS of 2, Serum Albumin < 0.85 x LLN, weight loss >10% in the preceding 6 months, FEV1 < 1.0. Subjects must not have malignant pleural effusions, CNS metastases and must not have received any prior chemotherapy or radiotherapy for lung cancer. Subjects will be treated with pemetrexed 500mg/m2 administered intravenously over approximately 10-minutes on Day 1 of a 21-day cycle x 3 cycles with concurrent radiation. After completion of treatment, subjects will be followed for progression and overall survival up to 5 years.