Intervention: Selumetinib
Trial phase: Phase 2
ATC code: L01EE04
SMILES: Cn1cnc2c(F)c(Nc3ccc(Br)cc3Cl)c(C(=O)NOCCO)cc21
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 28
Group description: Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

selumetinib: Given orally

laboratory biomarker analysis: Correlative studies
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