A Randomized, Phase II Trial of Crizotinib Plus Pemetrexed Versus Pemetrexed Monotherapy in ALK-Positive Non-Squamous NSCLC Patients Who Have Progressed Systemically After Previous Clinical Benefit from Crizotinib Monotherapy

Stage IV, ALK positive, non-squamous non-small cell lung cancer; progressed after attaining clinical benefit with crizotinib (at 250 mg BID for at least 90 days); pemetrexed naive; measurable disease; no brain mets (except for asymptomatic controlled mets off steroids or anticonvulsants for 14 days; palliative RT to non-target lesions ok; no major surgery within 28 days prior to reg; no exposure to HSP90 inhibitors or non-crizotinib ALK inhibitors; offered participation in translational medicine studies; ANC >/= 1500, PLT >/= 100,000, Hgb >/= 9, bili </= 2 x IULN, either AST or ALT </= 2.5 x IULN, estimated or measured glomerular filtration rate >/= 45, testosterone obtained for male pts; Zubrod 0-2; able to swallow capsules; QTC interval </= 480 msec on EKG (pts w/congenital long QT syndrome not eligible).