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

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)

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

Study Overview

• Status: Completed
• Conditions: Advanced or Metastatic HCC
• Intervention / Treatment: Drug: GC33

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC/Norris Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Center at the Detroit Medical Center
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Methodist Hospital
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute at the Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: GC33; IV administration at 4 escalating dose levels.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the safety and tolerability of escalating doses of GC33	Continuously

Secondary Outcome Measures

Outcome Measure	Time Frame
Characterize the pharmacokinetics of GC33	Continuously
Perform a preliminary assessment of anti-tumor activity of GC33	Continuously

Collaborators and Investigators

• Sponsor: Chugai Pharmaceutical
• Investigators: Study Chair: Toshihiko Ohtomo, Chugai Pharmaceutical

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: September 1, 2008
• First Submitted That Met QC Criteria: September 2, 2008
• First Posted (Estimate): September 3, 2008

Study Record Updates

• Last Update Posted (Estimate): October 17, 2012
• Last Update Submitted That Met QC Criteria: October 15, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular
• Other Study ID Numbers: GC-001US