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

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Chugai Pharmaceutical
ClinicalTrials.gov Identifier:
NCT00976170
First received: September 9, 2009
Last updated: October 1, 2014
Last verified: October 2014
  Purpose

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 Intervention Phase
Hepatocellular Carcinoma
Drug: GC33(RO5137382)
Drug: Sorafenib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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).

Resource links provided by NLM:


Further study details as provided by Chugai Pharmaceutical:

Primary Outcome Measures:
  • Toxicity evaluation in accordance with CTCAE v3.0 [ Time Frame: Continuous ] [ Designated as safety issue: Yes ]
  • Dose limiting toxicity and maximum tolerated dose [ Time Frame: Continuous ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • RECIST criteria (version 1.0) for response evaluation by CT/MRI in target and non-target lesions of HCC [ Time Frame: every 2 months ] [ Designated as safety issue: No ]
  • Repeat-dose pharmacokinetic behavior of GC33 and Sorafenib [ Time Frame: Continuous ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: September 2009
Study Completion Date: September 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: GC33(RO5137382)
IV administration at 6 escalating dose levels.
Drug: Sorafenib
Oral administration at 400mg twice daily or 400mg once daily

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00976170

Locations
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
Taiwan
National Cheng Kung University Hospital
Tainan, Taiwan
National Taiwan Univercity Hospital
Taipei, Taiwan
Sponsors and Collaborators
Chugai Pharmaceutical
Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Chugai Pharmaceutical
ClinicalTrials.gov Identifier: NCT00976170     History of Changes
Other Study ID Numbers: GC-002US
Study First Received: September 9, 2009
Last Updated: October 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Chugai Pharmaceutical:
Advanced or metastatic HCC

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014