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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00976170
Recruitment Status : Completed
First Posted : September 14, 2009
Last Update Posted : October 3, 2014
Hoffmann-La Roche
Information provided by (Responsible Party):
Chugai Pharmaceutical

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: GC33(RO5137382) Drug: Sorafenib Phase 1

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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).
Study Start Date : September 2009
Actual Primary Completion Date : July 2013
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Sorafenib

Arm Intervention/treatment
Experimental: 1 Drug: GC33(RO5137382)
IV administration at 6 escalating dose levels.

Drug: Sorafenib
Oral administration at 400mg twice daily or 400mg once daily

Primary Outcome Measures :
  1. Toxicity evaluation in accordance with CTCAE v3.0 [ Time Frame: Continuous ]
  2. Dose limiting toxicity and maximum tolerated dose [ Time Frame: Continuous ]

Secondary Outcome Measures :
  1. RECIST criteria (version 1.0) for response evaluation by CT/MRI in target and non-target lesions of HCC [ Time Frame: every 2 months ]
  2. Repeat-dose pharmacokinetic behavior of GC33 and Sorafenib [ Time Frame: Continuous ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00976170

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United States, California
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Florida
University of Miami
Miami, Florida, United States
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
National Cheng Kung University Hospital
Tainan, Taiwan
National Taiwan Univercity Hospital
Taipei, Taiwan
Sponsors and Collaborators
Chugai Pharmaceutical
Hoffmann-La Roche
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Chugai Pharmaceutical Identifier: NCT00976170    
Other Study ID Numbers: GC-002US
First Posted: September 14, 2009    Key Record Dates
Last Update Posted: October 3, 2014
Last Verified: October 2014
Keywords provided by Chugai Pharmaceutical:
Advanced or metastatic HCC
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action