A Phase I, Open-Label, Multi-center, Dose-escalation Study of the Safety, Tolerability, and Pharmacokinetics of GC33 in Combination With Sorafenib (Nexavar®) in Patients With Advanced or Metastatic Hepatocellular Carcinoma (HCC).
- Signed written Institutional Review Board/Ethical Committee approved informed consent
- Male or female ≥18 years old.
- Life expectancy ≥3 months.
- ECOG Performance Status of 0-1.
- Histologically confirmed hepatocellular carcinoma.
- Not a candidate for curative treatments.
- Child-Pugh A
- Hematological, Biochemical and Organ Function:
- AST (SGOT): ≤5.0 × ULN,
- ALT (SGPT): ≤5.0 × ULN,
- Total Bilirubin: ≤1.5mg/dL,
- Platelets: ≥100,000/μL,
- Absolute Neutrophil Count: ≥1,500/μL,
- Serum creatinine: ≤2.0 × ULN,
- PT-INR: ≤2.0
- Ability to provide a tumor tissue sample either by:
- A formalin fixed paraffin embedded block sample within 12 months prior to
informed consent for HCC diagnosis
- Undergo a biopsy to confirm HCC diagnosis
- Measurable disease.
- Child-Pugh B or C
- Patient who have taken Sorafenib previously.
- Difficulty or inability to swallow pills.
- Pregnant or lactating women or women of child-bearing potential and men of
childbearing potential not willing to use effective means of contraception.
- Patients known to be positive for Human immunodeficiency virus infection.
- Active infectious diseases requiring treatment except for hepatitis B and C.
- Other malignancies within the last 5 years.
- History of transplantation (organ, bone marrow transplantation, Peripheral blood stem
cell transplantation, etc.).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
- Patients with known brain metastases or other central nervous system
- Uncontrolled hypertension defined as systolic blood pressure >150 mmhg or diastolic
blood pressure >90 mmHg, despite optimal medical management.
- Non-tumor related thrombolic or embolic events such as a cerebrovascular accident
including transient ischemic attacks within the past 6 months.
- Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 3, any other hemorrhage/bleeding
event ≥ CTCAE Grade 4 within 4 weeks of first dose of study drug.
- Serious non-healing wound, ulcer, or bone fracture.
- Patients who received major surgery, local therapy for HCC, chemotherapy,
radiotherapy, hormone-therapy, immunotherapy, or another investigational drug within
4 weeks prior to Day 1(6 weeks for nitrosoureas, mitomycin, and bevacizumab; 1 week
for tumor biopsy).
- Patients who received the following treatments within 2 weeks prior to Day 1:
- Anticoagulant or thrombolytic agents for therapeutic purposes,
- Systemic anti-viral therapy for hepatitis C and Interferon therapy for hepatitis
- Blood transfusion including all blood products
- Known history of hypersensitivity to similar agents.
- Patients receiving any medications or substances that are inducers of CYP3A4 are
ineligible: rifampin, St. John's wort, phenytoin, carbamazepine, phenobarbital and
- Any psychological, familial, sociological or geographical condition potentially
hampering compliance with the study protocol requirements and/or follow-up
procedures; those conditions should be discussed with the patient before trial entry.