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

Chugai Pharmaceutical

Status and phase

Completed

Phase 1

Conditions

Advanced or Metastatic HCC

Treatments

Drug: GC33

Study type

Interventional

Funder types

Industry

Identifiers

NCT00746317

GC-001US

Details and patient eligibility

About

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

Full 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.

Enrollment

27 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.