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

This is an interventional treatment trial for Liver and Intrahepatic Biliary Tract Cancer Read More

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