Advanced or Metastatic HCC
Conditions
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.
Interventions
DRUGGC33
IV administration at 4 escalating dose levels.
Sponsors
Chugai Pharmaceutical
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine the safety and tolerability of escalating doses of GC33 | Continuously |
Secondary
| Measure | Time frame |
|---|---|
| Characterize the pharmacokinetics of GC33 | Continuously |
| Perform a preliminary assessment of anti-tumor activity of GC33 | Continuously |
Countries
United States
Outcome results
None listed