Clinical trial NCT00746317: A Phase I Study of GC33 in Advanced or Metastatic Liver Cancer (Hepatocellular Carcinoma)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced or Metastatic HCC
Lead sponsor: Chugai Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2008-09-03
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Determine the safety and tolerability of escalating doses of GC33
timeFrame: Continuously
Secondary outcomes:
measure: Characterize the pharmacokinetics of GC33
timeFrame: Continuously
measure: Perform a preliminary assessment of anti-tumor activity of GC33
timeFrame: Continuously
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Center at the Detroit Medical Center
state: Michigan
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Houston
country: United States
facility: Methodist Hospital
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute at the Swedish Medical Center
state: Washington
Study officials:
affiliation: Chugai Pharmaceutical
name: Toshihiko Ohtomo
role: STUDY_CHAIR
References: