Phase II Trial of SOM230 in Patients With Unresectable Hepatocellular Carcinoma

Inclusion Criteria

• Diagnosis of unresectable HCC by either:
• Histopathology or
• Elevated serum Alpha-fetoprotein (AFP) >400 ng/ml and findings on magnetic resonance imaging (MRI) or CT scans characteristic of a primary liver tumor.
• Findings on MRI or CT scans characteristic of a primary liver tumor in patients with cirrhosis
• Tumors at least 1 cm or greater
• Age ≥ 18 years.
• Minimum of four weeks since any major surgery, completion of radiation,or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy).
• Patients may have progressed on sorafenib or refused or were intolerant of sorafenib. A maximum of 2 prior lines of systemic therapy (including chemotherapy or targeted therapy) will be allowed. Prior locoregional therapy such as surgery, radiofrequency ablation or transarterial chemoembolization are also allowed (these will not be counted as systemic therapy), provided that progression has been documented after these therapies, and at least 4 weeks have elapsed since the last therapy.
• Karnofsky performance status (KPS) of 80 or Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life expectancy 12 weeks or more.
• Adequate bone marrow function as shown by: Absolute neutrophil count (ANC) ≥ 1.2 x 10^9/L, Platelets ≥ 50 x 10^9/L
• Adequate liver function as shown by: serum bilirubin 7% or =8% despite therapy) or a fasting plasma glucose > 1.5 ULN. Note: At the principle investigator's discretion, non-eligible patients can be re-screened after adequate medical therapy has been instituted.
• Patients with symptomatic cholelithiasis
• Patients who have congestive heart failure (NYHA Class III or IV), unstable angina,sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment.
• Patients who are at high risk for cardiac arrhythmias as defined by any of the following:
• Baseline QTcF > 470 msec
• History of syncope or family history of idiopathic sudden death or long QT syndrome
• Sustained or clinically significant cardiac arrhythmias
• Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade atrioventricular block (AV) block
• Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by uncontrolled diabetes, or Parkinson's disease), HIV, uncontrolled hypothyroidism or cardiac failure
• Concomitant medication(s) known to increase the QT interval (see Appendix II)
• Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result (ELISA and Western blot).
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• Severely impaired lung function
• Any active (acute or chronic) or uncontrolled infection/ disorders.
• Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy
• Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to administration of pasireotide). Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
• Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR formulations
• History of noncompliance to medical regimens
• Patients unwilling to or unable to comply with the protocol or unable to give informed consent.
• Patients with baseline Alanine trans