Randomized Phase II Trial of Single Agent MEK Inhibitor Trametinib Vs 5-Fluorouracil or Capecitabine in Refractory Advanced Biliary Cancer

Histologically or cytologically documented carcinoma primary to intra- or extra-hepatic biliary system or gall bladder with clinical/radiologic evidence of unresectable, locally advanced, or metastatic disease. Must have measurable disease. Must have completed prior chemotherapy at least 21 days prior to registration AND experienced progression to no more than 1 prior regimen of systemic chemo OR patients who received adjuvant chemo and had evidence of recurrence w/in 6 mo of completion of treatment. Must not have been treated with prior MEK inhibitors. Prior 5-FU or capecitabine allow only if given as radiosensitizer concurrently at least 12 wks prior to reg or if given as part of adjuvant therapy >/= 12 mo prior to enrollment. No plans to receive concurrent chemo, hormonal therapy, radiotherapy, immunotherapy, or other type of therapy for cancer. Must be >/= 28 days since cryotherapy, radiation therapy, radiofrequency ablation, therasphere, ethanol injection, TACE or photodynamic therapy. Zubrod PS 0-1. Within 28 days prior to reg: ANC > 1000/uL; platelets > 100,000/uL; total bilirubin </= 2.0 x IULN; AST & ALT both </= 3.0 x IULN; if liver mets present AST & ALT must be </= 5 x IULN. If pt has had decompression of biliary tree w/in 14 days stability of bilirubin level needs to be confirmed w/2 measurements. Serum creatinine </= 1.5 mg/dL or calculated creatinine clearance >/= 60 ml/min w/in 28 days prior to reg. Pts w/known history or current evidence of retinal vein occlusion or retinal pigment epithelial detachment are not eligible. LVEF >/= ILLN w/in 28 days prior to reg. Must not have uncontrolled/clinically significant cardiovascular disease including: MI w/in 6mo, uncontrolled angina w/in 6mo, class II-IV NYHA CHF, Grade 3 cardiac valve dysfunction, cardiac arrhythmia not controlled by meds, history of stroke or TIA w/in 6mo, history of ATE of any type in past 6 mo, treatment-refractory hypertension, known intra-cardiac defibrillators, or known cardiac metastases. QTcF