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

Sponsor

Chugai Pharmaceutical (Industry)

Overall Status

Completed

CT.gov ID

NCT00746317

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Advanced or Metastatic HCC	Drug: GC33	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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)

Study Start Date :

Sep 1, 2008

Actual Primary Completion Date :

Oct 1, 2010

Actual Study Completion Date :

Oct 1, 2012

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: 1

Drug: GC33

IV administration at 4 escalating dose levels.

Outcome Measures

Primary Outcome Measures

Determine the safety and tolerability of escalating doses of GC33 [Continuously]

Secondary Outcome Measures

Characterize the pharmacokinetics of GC33 [Continuously]
Perform a preliminary assessment of anti-tumor activity of GC33 [Continuously]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
4	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
5	Karmanos Cancer Center at the Detroit Medical Center	Detroit	Michigan	United States	48201
6	Washington University	St. Louis	Missouri	United States	63110
7	Columbia University Medical Center	New York	New York	United States	10032
8	Methodist Hospital	Houston	Texas	United States	77030
9	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Chugai Pharmaceutical

ClinicalTrials.gov Identifier:

NCT00746317

Other Study ID Numbers:

GC-001US

First Posted:

Sep 3, 2008

Last Update Posted:

Oct 17, 2012

Last Verified:

Oct 1, 2012

Additional relevant MeSH terms:

Carcinoma, Hepatocellular

Study Results

No Results Posted as of Oct 17, 2012