Phase II Trial of SOM230 in Patients With Unresectable Hepatocellular Carcinoma
Condition: Hepatocellular Carcinoma
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: SOM230
Intervention description: Patients will be given a starting of 60mg of SOM230 via injection, intramuscularly every 28 days.
Intervention MeSH terms: Pasireotide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hepatocellular Carcinoma; HCC; SOM230; Pasireotide LAR

Summary:

      The hypothesis of this clinical trial is that hepatocellular carcinomas contain somatostatin
      receptors which make them sensitive to the inhibitory effects of a new somatostatin analog,
      SOM230. This analog has greater and broader binding affinity to somatostatin receptors
      compared to the current drug in use, sandostatin LAR. Thus, SOM230 has the potential to be
      more effective in the treatment of patients with hepatocellular carcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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

          2. Age ≥ 18 years.

          3. 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).

          4. 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.

          5. Karnofsky performance status (KPS) of 80 or Eastern Cooperative Oncology Group (ECOG)
             performance status of 0 or 1.

          6. Life expectancy 12 weeks or more.

          7. Adequate bone marrow function as shown by: Absolute neutrophil count (ANC) ≥ 1.2 x
             10^9/L, Platelets ≥ 50 x 10^9/L

          8. Adequate liver function as shown by: serum bilirubin < 1.5x upper limit of normal
             (ULN) and serum transaminases activity ≤ 3 x ULN. Serum PT =< 16 seconds.

          9. Adequate renal function as shown by serum creatinine ≤ 1.5 x ULN.

         10. Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x
             ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only
             be included after initiation (can start after one day of initiation of lipid lowering
             drug) of appropriate lipid lowering medication.

         11. Women of childbearing potential must have a negative serum or urine pregnancy test
             within 14 days of the administration of the first study treatment. Women must not be
             lactating. Both men and women of childbearing potential must be advised of the
             importance of using effective birth control measures during the course of the study.

         12. Signed informed consent to participate in the study must be obtained from patients
             after they have been fully informed of the nature and potential risks by the
             investigator (or his/her designee) with the aid of written information.

         13. Child's A and early Child's B (no more than 7 points on the Child Pugh
             Classification).

         14. Measurable disease by CT scan with contrast. If evaluable disease or measurable
             disease has been previously treated, this must show signs of tumor progression by CT.
             Measurable disease and evaluable disease will be defined by the RECISTguidelines (see
             section 9.0).

         15. Patients with cirrhosis either radiologically or pathology with findings either by CT
             scan or MRI characteristic of primary liver cancer are eligible.

        Exclusion Criteria:

          1. Prior octreotide therapy or any somatostatin analog.

          2. Chronic treatment with systemic steroids or another immunosuppressive agent.

          3. Patients should not receive immunization with attenuated live vaccines during study
             period or within 1 week of study entry (ie. within 1 week of signing the informed
             consent).

          4. Uncontrolled brain or leptomeningeal metastases, including patients who continue to
             require glucocorticoids for brain or leptomeningeal metastases.

          5. Patients with prior or concurrent malignancy except for the following: adequately
             treated basal cell or squamous cell skin cancer, or other adequately treated in situ
             cancer, or any other cancer from which the patient has been disease free for five
             years.

          6. Patients with uncontrolled diabetes mellitus (defined as HgA1c > 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.

          7. Patients with symptomatic cholelithiasis

          8. 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.

          9. 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)

         10. 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).

         11. 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

         12. 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.

         13. Known hypersensitivity to somatostatin analogues or any component of the pasireotide
             or octreotide LAR formulations

         14. History of noncompliance to medical regimens

         15. Patients unwilling to or unable to comply with the protocol or unable to give informed
             consent.

         16. Patients with baseline Alanine transaminase (ALT) or Aspartate transaminase (AST) > 3x
             ULN.

         17. Patients with baseline serum bilirubin > 1.5 x ULN.

         18. Prothrombin time (PT) > 16 seconds and/or partial thromboplastin time (PTT) > 1.5 x
             ULN

         19. History of or current alcohol misuse/abuse within the past 12 months.

         20. Known gallbladder or bile duct disease, acute or chronic pancreatitis.