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

Primary Purpose

Hepatocellular Carcinoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GC33(RO5137382)
Sorafenib
Sponsored by
Chugai Pharmaceutical
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Advanced or metastatic HCC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • California Pacific Medical Center
  • University of Miami
  • Memorial Sloan-Kettering Cancer Center
  • University of North Carolina
  • Fox Chase Cancer Center
  • National Cheng Kung University Hospital
  • National Taiwan Univercity Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Outcomes

Primary Outcome Measures

Toxicity evaluation in accordance with CTCAE v3.0
Dose limiting toxicity and maximum tolerated dose

Secondary Outcome Measures

RECIST criteria (version 1.0) for response evaluation by CT/MRI in target and non-target lesions of HCC
Repeat-dose pharmacokinetic behavior of GC33 and Sorafenib

Full Information

First Posted
September 9, 2009
Last Updated
October 1, 2014
Sponsor
Chugai Pharmaceutical
Collaborators
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00976170
Brief Title
Study of GC33 and Sorafenib in Combination in Advanced or Metastatic Liver Cancer (Hepatocellular Carcinoma)
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 Type
Interventional

2. Study Status

Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
September 2009 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chugai Pharmaceutical
Collaborators
Hoffmann-La Roche

4. Oversight

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Advanced or metastatic HCC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
GC33(RO5137382)
Intervention Description
IV administration at 6 escalating dose levels.
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Intervention Description
Oral administration at 400mg twice daily or 400mg once daily
Primary Outcome Measure Information:
Title
Toxicity evaluation in accordance with CTCAE v3.0
Time Frame
Continuous
Title
Dose limiting toxicity and maximum tolerated dose
Time Frame
Continuous
Secondary Outcome Measure Information:
Title
RECIST criteria (version 1.0) for response evaluation by CT/MRI in target and non-target lesions of HCC
Time Frame
every 2 months
Title
Repeat-dose pharmacokinetic behavior of GC33 and Sorafenib
Time Frame
Continuous

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111-2497
Country
United States
Facility Name
National Cheng Kung University Hospital
City
Tainan
Country
Taiwan
Facility Name
National Taiwan Univercity Hospital
City
Taipei
Country
Taiwan

12. IPD Sharing Statement

Citations:
PubMed Identifier
28120036
Citation
Abou-Alfa GK, Yen CJ, Hsu CH, O'Donoghue J, Beylergil V, Ruan S, Pandit-Taskar N, Gansukh B, Lyashchenko SK, Ma J, Wan P, Shao YY, Lin ZZ, Frenette C, O'Neil B, Schwartz L, Smith-Jones PM, Ohtomo T, Tanaka T, Morikawa H, Maki Y, Ohishi N, Chen YC, Agajanov T, Boisserie F, Di Laurenzio L, Lee R, Larson SM, Cheng AL, Carrasquilo JA. Phase Ib study of codrituzumab in combination with sorafenib in patients with non-curable advanced hepatocellular carcinoma (HCC). Cancer Chemother Pharmacol. 2017 Feb;79(2):421-429. doi: 10.1007/s00280-017-3241-9. Epub 2017 Jan 24.
Results Reference
derived

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

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