A Phase I Study of GC33 in Advanced or Metastatic Liver Cancer (Hepatocellular Carcinoma)
Primary Purpose
Advanced or Metastatic HCC
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GC33
Sponsored by

About this trial
This is an interventional treatment trial for Advanced or Metastatic HCC
Eligibility Criteria
Inclusion Criteria:
- Signed written Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form
- Male or female ≥ 18 years old.
- Life expectancy ≥ 3 months.
- ECOG Performance Status of 0-1.
- Histologically confirmed hepatocellular carcinoma (without fibrolamellar subtype).
- Not a candidate for curative treatments.
- Child-Pugh A or B.
Hematological, Biochemical and Organ Function:
- AST (SGOT): ≤ 5.0 × ULN
- ALT (SGPT): ≤ 5.0 × ULN
- Total Bilirubin: ≤ 3.0 × ULN
- Platelets: ≥ 50,000/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 sample obtained within 3 months prior to informed consent for HCC diagnosis. Resection samples are not acceptable.
- undergo a biopsy to confirm HCC diagnosis
- At least one measurable lesion based on Response Evaluation Criteria In Solid Tumors criteria.
(Extension Phase)
- Signed written Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form.
- Male or female ≥ 18 years old.
- Life expectancy ≥ 3 months.
- ECOG Performance Status of 0-1.
- Histologically confirmed hepatocellular carcinoma (without fibrolamellar subtype).
- 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: ≤ 3.0 × ULN
- Platelets: ≥ 50,000/μL
- Absolute Neutrophil Count: ≥ 1,500/μL
- Serum creatinine: ≤ 2.0 × ULN
- PT-INR: ≤ 2.0
IHC confirmed GPC3-positive HCC tumor tissue. Tumor tissue sample may be provided by:
- A formalin fixed paraffin embedded block sample within 12 months prior to informed consent for HCC diagnosis;
- Unstained slides obtained within 3 months prior to informed consent for HCC diagnosis;
- Undergo biopsy to confirm GPC3-positive HCC.
- Resection samples are not acceptable.
- At least one measurable lesion based on Response Evaluation Criteria In Solid Tumors criteria.
Exclusion Criteria:
- Child-Pugh C.
- 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.).
- Patients with significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug.
- Patients with brain metastases, other central nervous system or other psychiatric disease.
- 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.
Patients who received the following treatments within 2 weeks prior to Day1:
- Anticoagulant or thrombolytic agents for therapeutic purposes.
- Systemic anti-viral therapy for hepatitis C/cirrhosis.
- Blood transfusion
- History of hypersensitivity to similar agents.
- Patient is unable to comply with the requirements of the protocol and/or follow-up procedures.
(Extension Phase)
- Child-Pugh B or C.
- 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.).
- Patients with significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug.
- Patients with brain metastases, other central nervous system or other psychiatric disease.
- 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.
Patients who received the following treatments within 2 weeks prior to Day 1:
- Anticoagulations or thrombolytic agents for therapeutic purposes.
- Systemic anti-viral therapy for hepatitis C/cirrhosis.
- Blood transfusion
- History of hypersensitivity to similar agents.
- Patient is unable to comply with the requirements of the protocol and/or follow-up procedures.
- IHC confirmed GPC3-negative HCC tumor tissue.
Sites / Locations
- USC/Norris Comprehensive Cancer Center
- Massachusetts General Hospital
- Beth Israel Deaconess Medical Center
- Dana-Farber Cancer Institute
- Karmanos Cancer Center at the Detroit Medical Center
- Washington University
- Columbia University Medical Center
- Methodist Hospital
- Swedish Cancer Institute at the Swedish Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
Primary Outcome Measures
Determine the safety and tolerability of escalating doses of GC33
Secondary Outcome Measures
Characterize the pharmacokinetics of GC33
Perform a preliminary assessment of anti-tumor activity of GC33
Full Information
NCT ID
NCT00746317
First Posted
September 1, 2008
Last Updated
October 15, 2012
Sponsor
Chugai Pharmaceutical
1. Study Identification
Unique Protocol Identification Number
NCT00746317
Brief Title
A Phase I Study of GC33 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 Administered Weekly in Patients With Advanced or Metastatic Hepatocellular Carcinoma (HCC)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
September 2008 (undefined)
Primary Completion Date
October 2010 (Actual)
Study Completion Date
October 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chugai Pharmaceutical
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This phase I trial is studying the safety and best dose of GC33 in patients with advanced or metastatic liver cancer.
Detailed Description
This is a Phase I open-label dose escalation study of GC33 in patients with advanced or metastatic HCC. This study is designed to evaluate safety, tolerability, pharmacokinetics, and preliminary assessment of anti-tumor activity. 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
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
27 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
GC33
Intervention Description
IV administration at 4 escalating dose levels.
Primary Outcome Measure Information:
Title
Determine the safety and tolerability of escalating doses of GC33
Time Frame
Continuously
Secondary Outcome Measure Information:
Title
Characterize the pharmacokinetics of GC33
Time Frame
Continuously
Title
Perform a preliminary assessment of anti-tumor activity of GC33
Time Frame
Continuously
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed written Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form
Male or female ≥ 18 years old.
Life expectancy ≥ 3 months.
ECOG Performance Status of 0-1.
Histologically confirmed hepatocellular carcinoma (without fibrolamellar subtype).
Not a candidate for curative treatments.
Child-Pugh A or B.
Hematological, Biochemical and Organ Function:
AST (SGOT): ≤ 5.0 × ULN
ALT (SGPT): ≤ 5.0 × ULN
Total Bilirubin: ≤ 3.0 × ULN
Platelets: ≥ 50,000/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 sample obtained within 3 months prior to informed consent for HCC diagnosis. Resection samples are not acceptable.
undergo a biopsy to confirm HCC diagnosis
At least one measurable lesion based on Response Evaluation Criteria In Solid Tumors criteria.
(Extension Phase)
Signed written Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form.
Male or female ≥ 18 years old.
Life expectancy ≥ 3 months.
ECOG Performance Status of 0-1.
Histologically confirmed hepatocellular carcinoma (without fibrolamellar subtype).
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: ≤ 3.0 × ULN
Platelets: ≥ 50,000/μL
Absolute Neutrophil Count: ≥ 1,500/μL
Serum creatinine: ≤ 2.0 × ULN
PT-INR: ≤ 2.0
IHC confirmed GPC3-positive HCC tumor tissue. Tumor tissue sample may be provided by:
A formalin fixed paraffin embedded block sample within 12 months prior to informed consent for HCC diagnosis;
Unstained slides obtained within 3 months prior to informed consent for HCC diagnosis;
Undergo biopsy to confirm GPC3-positive HCC.
Resection samples are not acceptable.
At least one measurable lesion based on Response Evaluation Criteria In Solid Tumors criteria.
Exclusion Criteria:
Child-Pugh C.
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.).
Patients with significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug.
Patients with brain metastases, other central nervous system or other psychiatric disease.
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.
Patients who received the following treatments within 2 weeks prior to Day1:
Anticoagulant or thrombolytic agents for therapeutic purposes.
Systemic anti-viral therapy for hepatitis C/cirrhosis.
Blood transfusion
History of hypersensitivity to similar agents.
Patient is unable to comply with the requirements of the protocol and/or follow-up procedures.
(Extension Phase)
Child-Pugh B or C.
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.).
Patients with significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug.
Patients with brain metastases, other central nervous system or other psychiatric disease.
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.
Patients who received the following treatments within 2 weeks prior to Day 1:
Anticoagulations or thrombolytic agents for therapeutic purposes.
Systemic anti-viral therapy for hepatitis C/cirrhosis.
Blood transfusion
History of hypersensitivity to similar agents.
Patient is unable to comply with the requirements of the protocol and/or follow-up procedures.
IHC confirmed GPC3-negative HCC tumor tissue.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Toshihiko Ohtomo
Organizational Affiliation
Chugai Pharmaceutical
Official's Role
Study Chair
Facility Information:
Facility Name
USC/Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Karmanos Cancer Center at the Detroit Medical Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Washington University
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Swedish Cancer Institute at the Swedish Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Phase I Study of GC33 in Advanced or Metastatic Liver Cancer (Hepatocellular Carcinoma)
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