Study of GC33 and Sorafenib in Combination in Advanced or Metastatic Liver Cancer (Hepatocellular Carcinoma)

Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase I, Open-Label, Multi-center, Dose-escalation Study of the Safety, Tolerability, and Pharmacokinetics of GC33 in Combination With Sorafenib (Nexavar®) in Patients With Advanced or Metastatic Hepatocellular Carcinoma (HCC).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00976170
• Other study ID #: GC-002US
• Status: Completed
• Phase: Phase 1
• First received: September 9, 2009
• Last updated: October 1, 2014
• Start date: September 2009
• Est. completion date: September 2014

Study information

• Verified date: October 2014
• Source: Chugai Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Description:

This is a Phase I open-label dose escalation study of GC33 in combination with Sorafenib in patients with advanced or metastatic HCC. This study is designed to evaluate safety, tolerability, pharmacokinetics, and efficacy. Enrollment will proceed until a maximum tolerated dose (MTD) and a recommended Phase II dose has been established.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: September 2014
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Signed written Institutional Review Board/Ethical Committee approved informed consent form.

• Male or female =18 years old.

• Life expectancy =3 months.

• ECOG Performance Status of 0-1.

• Histologically confirmed hepatocellular carcinoma.

• 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: =1.5mg/dL,

• Platelets: =100,000/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 formalin fixed paraffin embedded block sample within 12 months prior to informed consent for HCC diagnosis

• Undergo a biopsy to confirm HCC diagnosis

• Measurable disease.

Exclusion Criteria:

• Child-Pugh B or C

• Patient who have taken Sorafenib previously.

• Difficulty or inability to swallow pills.

• 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.).

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements..

• Patients with known brain metastases or other central nervous system disease/disorders.

• Uncontrolled hypertension defined as systolic blood pressure >150 mmhg or diastolic blood pressure >90 mmHg, despite optimal medical management.

• Non-tumor related thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.

• Pulmonary hemorrhage/bleeding event = CTCAE Grade 3, any other hemorrhage/bleeding event = CTCAE Grade 4 within 4 weeks of first dose of study drug.

• Serious non-healing wound, ulcer, or bone fracture.

• 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(6 weeks for nitrosoureas, mitomycin, and bevacizumab; 1 week for tumor biopsy).

• Patients who received the following treatments within 2 weeks prior to Day 1:

• Anticoagulant or thrombolytic agents for therapeutic purposes,

• Systemic anti-viral therapy for hepatitis C and Interferon therapy for hepatitis B,

• Blood transfusion including all blood products

• Known history of hypersensitivity to similar agents.

• Patients receiving any medications or substances that are inducers of CYP3A4 are ineligible: rifampin, St. John's wort, phenytoin, carbamazepine, phenobarbital and dexamethasone.

• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• GC33(RO5137382)
IV administration at 6 escalating dose levels.
• Sorafenib
Oral administration at 400mg twice daily or 400mg once daily

Locations

Country	Name	City	State
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan Univercity Hospital	Taipei
United States	University of North Carolina	Chapel Hill	North Carolina
United States	University of Miami	Miami	Florida
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	California Pacific Medical Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Chugai Pharmaceutical	Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity evaluation in accordance with CTCAE v3.0		Continuous	Yes
Primary	Dose limiting toxicity and maximum tolerated dose		Continuous	Yes
Secondary	RECIST criteria (version 1.0) for response evaluation by CT/MRI in target and non-target lesions of HCC		every 2 months	No
Secondary	Repeat-dose pharmacokinetic behavior of GC33 and Sorafenib		Continuous	No