Selumetinib in Treating Patients With Locally Advanced or Metastatic Liver Cancer
Condition: Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer
MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
Intervention: selumetinib; pharmacological study
Intervention description: Given orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying selumetinib to see how well it works in treating patients
      with locally advanced or metastatic liver cancer. Selumetinib may stop the growth of tumor
      cells by blocking some of the enzymes needed for their growth.
    

Eligibility criteria:

        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