Selumetinib in Treating Patients With Locally Advanced or Metastatic Liver Cancer

Inclusion Criteria

• •Meets 1 of the following criteria:
• •* Histologically or cytologically confirmed hepatocellular carcinoma
• •* Serum alpha fetoprotein \> 1000ng/dL with characteristic imaging findings coupled with the appropriate clinical scenario (i.e., chronic hepatitis and/or cirrhosis)
• •* Child's A or B cirrhosis allowed
• •* If Child's B cirrhosis is present, the patient may not have significant encephalopathy or ascites that requires paracentesis and must meet laboratory criteria (i.e., well-compensated Child's B)
• •Metastatic disease (including any proven lymph node metastases) or localized disease not amenable to potentially curative transplant/locoregional/surgical therapy as determined by a qualified surgeon or tumor board
• •Measurable disease, defined as at least one unidimensionally measurable ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
• •No known brain metastases
• •ECOG performance status ≤ 2
• •Life expectancy \> 3 months
• •Leukocytes ≥ 3,000/mm³
• •Absolute neutrophil count ≥ 1,500/mm³
• •Platelets ≥ 75,000/mm³
• •Total bilirubin \< 2 times upper limit of normal (ULN)
• •AST/ALT \< 5 times ULN
• •Creatinine \< 1.5 mg/dL or creatinine clearance ≥ 60 mL/min
• •INR \< 1.4
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception before, during, and for 4 weeks after completion of study treatment
• •Willing to undergo protocol-required tumor biopsies (patients must also be able to have any anticoagulation held for an appropriate period of time)
• •No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD6244 or its excipient Captisol®
• •No refractory nausea and vomiting or chronic gastrointestinal diseases (e.g., inflammatory bowel disease) that would preclude adequate absorption
• •No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
• •No active illicit substance or alcohol abuse
• •Able to understand and willing to sign a written informed consent document
• •Recovered from prior therapy
• •At least 4 weeks since prior chemo embolization, radio embolization (90Y microspheres), resection, or radio frequency/cryoablation
• •* Must have measurable disease outside the treated area or unequivocal evidence of disease progression within the treated area
• •More than 4 weeks since prior radio therapy or major surgery
• •No prior organ transplantation
• •No prior systemic chemotherapy
• •No prior sorafenib
• •No prior therapeutic antibody or experimental systemic therapy (oral or intravenous)
• •No prior hepatic artery infusion of chemotherapy
• •No prior mitogen-activated protein kinase inhibitor
• •No prior significant bowel resection that would preclude adequate absorption
• •No concurrent fruit or juice of the grapefruit during AZD6244 therapy
• •No concurrent anti retroviral therapy for HIV-positive patients
• •No other concurrent investigational or commercial agents or therapies for this cancer