Study of GC33 and Sorafenib in Combination in Advanced or Metastatic Liver Cancer (Hepatocellular Carcinoma)

Study Overview
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Brief Summary
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This phase I trial is studying the safety and best dose of GC33 and Sorafenib in combination in patients with advanced or metastatic liver cancer.

Detailed Description
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This is a Phase I open-label dose escalation study of GC33 in combination with Sorafenib in patients with advanced or metastatic HCC. This study is designed to evaluate safety, tolerability, pharmacokinetics, and efficacy. Enrollment will proceed until a maximum tolerated dose (MTD) and a recommended Phase II dose has been established.

Official Title
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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).

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: GC33(RO5137382)
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written Institutional Review Board/Ethical Committee approved informed consent form. 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. Exclusion Criteria: 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 study requirements.. Patients with known brain metastases or other central nervous system disease/disorders. 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 B, 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 dexamethasone. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: GC33(RO5137382)<br>* IV administration at 6 escalating dose levels.<br>Drug: Sorafenib<br>* Oral administration at 400mg twice daily or 400mg once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity evaluation in accordance with CTCAE v3.0 |  | Continuous | 
| Dose limiting toxicity and maximum tolerated dose |  | Continuous | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RECIST criteria (version 1.0) for response evaluation by CT/MRI in target and non-target lesions of HCC |  | every 2 months | 
| Repeat-dose pharmacokinetic behavior of GC33 and Sorafenib |  | Continuous | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced or metastatic HCC