A Phase I Study of GC33 in Advanced or Metastatic Liver Cancer (Hepatocellular Carcinoma)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Chugai Pharmaceutical
ClinicalTrials.gov Identifier:
NCT00746317
First received: September 1, 2008
Last updated: October 15, 2012
Last verified: October 2012
  Purpose

This phase I trial is studying the safety and best dose of GC33 in patients with advanced or metastatic liver cancer.


Condition Intervention Phase
Advanced or Metastatic HCC
Drug: GC33
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 Administered Weekly 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:
  • Determine the safety and tolerability of escalating doses of GC33 [ Time Frame: Continuously ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Characterize the pharmacokinetics of GC33 [ Time Frame: Continuously ] [ Designated as safety issue: No ]
  • Perform a preliminary assessment of anti-tumor activity of GC33 [ Time Frame: Continuously ] [ Designated as safety issue: No ]

Enrollment: 27
Study Start Date: September 2008
Study Completion Date: October 2012
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: GC33
IV administration at 4 escalating dose levels.

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.

  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 (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.
  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: NCT00746317

Locations
United States, California
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Karmanos Cancer Center at the Detroit Medical Center
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
United States, Texas
Methodist Hospital
Houston, Texas, United States, 77030
United States, Washington
Swedish Cancer Institute at the Swedish Medical Center
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Chugai Pharmaceutical
Investigators
Study Chair: Toshihiko Ohtomo Chugai Pharmaceutical
  More Information

No publications provided

Responsible Party: Chugai Pharmaceutical
ClinicalTrials.gov Identifier: NCT00746317     History of Changes
Other Study ID Numbers: GC-001US
Study First Received: September 1, 2008
Last Updated: October 15, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on July 24, 2014