Selumetinib in Treating Patients With Locally Advanced or Metastatic Liver Cancer

This is an interventional treatment trial for Adult Primary Hepatocellular Carcinoma Read More

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