Selumetinib in Treating Patients With Biliary Cancer That Cannot Be Removed By Surgery

Inclusion Criteria:

* Histologically confirmed biliary tract carcinoma

  * Surgically unresectable disease
* Meets any of the following criteria for biliary cancers only:

  * Received ≤ 1 prior systemic anticancer therapy, including chemoembolization
  * Received prior cryotherapy, radiofrequency ablation, ethanol injection, transarterial chemoembolization, or photodynamic therapy AND meets the following criteria:

    * More than 6 weeks have elapsed since any of the prior therapy described above
    * Indicator lesion(s) must be outside the area of prior treatment OR must demonstrate clear evidence of disease progression if the only indicator lesion is inside the prior treatment area
    * Indicator lesion must have clearly distinct edges on CT scan
  * Prior radiotherapy with or without the use of a fluoropyrimidine as a radiosensitizer is allowed, provided more than 12 weeks have elapsed since treatment
* Fresh or paraffin-embedded tissue from tumor blocks must be available for review
* Measurable disease, defined as ≥ 1 unidimensionally measurable lesion \> 20 mm by conventional techniques or \> 10 mm by spiral CT scan
* No known brain metastases
* Life expectancy \> 12 weeks
* ECOG performance status (PS) 0-1 or Karnofsky PS 70-100%
* ANC ≥ 1,500/μL
* Platelet count ≥ 75,000/μL
* Total bilirubin ≤ 2 times upper limit of normal(ULN)
* AST or ALT ≤ 3 times ULN
* Serum albumin ≥ 2.5 mg/dL
* INR ≤ 1.5 (not receiving anticoagulation therapy)
* Creatinine normal or creatinine clearance ≥ 60 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile women must use effective contraception during and for four weeks after the last dose of AZD6244
* Fertile men must use effective contraception during and for 16 weeks after the last dose of AZD6244
* No significant traumatic injury within the past 3 weeks
* No uncontrolled symptoms consistent with encephalopathy
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or its excipient, Captisol®
* No QTc interval \> 500 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., hypokalemia or family history of long QT interval syndrome), including NYHA class III-IV heart failure
* No other malignancy within the past 3 years, except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
* No refractory nausea and vomiting, chronic gastrointestinal disease (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
* No uncontrolled concurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situation that would limit compliance with study requirements
* No malignant hypertension within the past year
* No prior sorafenib or MEK inhibitors
* More than 4 weeks since prior chemotherapy, biologic therapy, or immunotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered to ≤ grade 1 adverse events
* No major surgery within the past 3 weeks
* No other concurrent investigational agents
* No concurrent requirement for medication that can prolong the QT interval
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No concurrent consumption of grapefruit or grapefruit juice