Selumetinib in Treating Patients With Biliary Cancer That Cannot Be Removed By Surgery
Condition: Liver and Intrahepatic Biliary Tract Cancer; Recurrent Extrahepatic Bile Duct Cancer; Unresectable Extrahepatic Bile Duct Cancer
MeSH terms: Biliary Tract Neoplasms; Bile Duct Neoplasms; Cholangiocarcinoma
Intervention: selumetinib; laboratory biomarker analysis
Intervention description: Given orally; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well selumetinib works in treating patients with biliary
      cancer that cannot be removed by surgery. Selumetinib may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        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