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

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

Detailed Description
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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.

Official Title
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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)

Conditions
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Advanced or Metastatic HCC

Intervention / Treatment
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* Drug: GC33


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: GC33<br>* IV administration at 4 escalating dose levels.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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