A Multi-center, Open-label Study of Oral ENMD-2076 for the Treatment of Patients With Advanced Fibrolamellar Carcinoma

Inclusion Criteria: * Histologically or cytologically confirmed advanced fibrolamellar carcinoma (FLC). * All forms of prior local therapy are allowed as long as patients have either a target lesion, which has not been treated with local therapy and/or the target lesion(s) within the field of the local-regional therapy has shown an increase of ≥ 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan. Local therapies including chemoembolization do not count as prior systemic therapy. * Are at least 4 weeks from major surgery and recovered. * At least one measureable lesion by RECIST 1.1. * Male or non-pregnant, non-breastfeeding female at least 18 years of age. Patients aged at 12\~18 years may be recruited but only at the site principle investigator's request and subject to Institutional Review Board (IRB) approval. * Has a pre-study echocardiogram or multi-gated acquisition (MUGA) scan with an actual left ventricular ejection fraction of greater than or equal to the institutional lower limit of normal within one month of initiating therapy. * Have clinically acceptable laboratory screening results within certain limits specified below: * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 times upper limit of normal (ULN) * Total bilirubin ≤ 3.0 x ULN * Creatinine ≤ 1.5 x ULN or Cr Cl \> 60 cc/min * Absolute neutrophil count ≥ 1500 cells/mm3 * Platelets ≥ 50,000/mm3 * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 for ≥ 16 years of age and a Lansky performance status of 70-100 for \< 16 years of age * Women and men of child producing potential must agree to use effective contraceptive methods prior to study entry, during study participation, and for at least 30 days after the last administration of study medication. A serum pregnancy test within 72 hours prior to the initiation of therapy will be required for women of childbearing potential. * Have the ability to understand the requirements of the study, provide written informed consent, which includes authorization for release of protected health information, abide by the study restrictions, and agree to return for the required assessments. Exclusion Criteria: * Have active, acute, or chronic clinically significant infections or bleeding within the last 6 months or previous thromboembolic or hemorrhagic events during anti angiogenic therapy. * Have uncontrolled hypertension (systolic blood pressure greater than 150 or diastolic blood pressure greater than 100) or history of congestive heart failure (AHA Grade 2 or higher). * Have active angina pectoris, stroke or recent myocardial infarction (within 6 months). * Have uncontrolled chronic atrial fibrillation. * Have chronic atrial fibrillation or QTc interval corrected for heart rate of greater than 470 msec in adults and 450 msec in pediatrics (\< 18 years). * Have additional uncontrolled serious medical or psychiatric illness that in the point of view of the investigator can render the patient unable to receive therapy or make it unsafe to receive therapy. * Require treatment with any of the exclusionary medications listed in Appendix D. * Known untreated or unstable central nervous system (CNS) metastatic disease. * Have persistent 2+ protein by urinalysis (patients with 2+ proteinuria that have a spot protein:creatinine ratio of less than 0.3 may be enrolled) or a history of nephrotic syndrome. * Subjects with history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present in the opinion of the investigator will not affect patient outcome in the setting of current FLC diagnosis.