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

NCT ID: NCT00976170

Last Updated: 2014-10-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2014-09-30

Brief 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.

Detailed 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.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

GC33(RO5137382)

Intervention Type: DRUG

IV administration at 6 escalating dose levels.

Sorafenib

Intervention Type: DRUG

Oral administration at 400mg twice daily or 400mg once daily

Interventions

GC33(RO5137382)

IV administration at 6 escalating dose levels.

Intervention Type: DRUG

Sorafenib

Oral administration at 400mg twice daily or 400mg once daily

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Chugai Pharmaceutical

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

California Pacific Medical Center

San Francisco, California, United States

University of Miami

Miami, Florida, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan Univercity Hospital

Taipei, , Taiwan

Countries

United States; Taiwan

References

Abou-Alfa GK, Yen CJ, Hsu CH, O'Donoghue J, Beylergil V, Ruan S, Pandit-Taskar N, Gansukh B, Lyashchenko SK, Ma J, Wan P, Shao YY, Lin ZZ, Frenette C, O'Neil B, Schwartz L, Smith-Jones PM, Ohtomo T, Tanaka T, Morikawa H, Maki Y, Ohishi N, Chen YC, Agajanov T, Boisserie F, Di Laurenzio L, Lee R, Larson SM, Cheng AL, Carrasquilo JA. Phase Ib study of codrituzumab in combination with sorafenib in patients with non-curable advanced hepatocellular carcinoma (HCC). Cancer Chemother Pharmacol. 2017 Feb;79(2):421-429. doi: 10.1007/s00280-017-3241-9. Epub 2017 Jan 24.

Reference Type: DERIVED

PMID: 28120036 (View on PubMed)

Other Identifiers

GC-002US

Identifier Type: -

Identifier Source: org_study_id