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

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).

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.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: GC33(RO5137382); Drug: Sorafenib

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • National Taiwan Univercity Hospital
• United States
  • California
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center
  • Florida
    • Miami, Florida, United States
      • University of Miami
  • New York
    • New York, New York, United States
      • Memorial Sloan-Kettering Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States
      • University of North Carolina
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111-2497
      • Fox Chase Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: GC33(RO5137382); IV administration at 6 escalating dose levels.; Drug: Sorafenib; Oral administration at 400mg twice daily or 400mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Toxicity evaluation in accordance with CTCAE v3.0	Continuous
Dose limiting toxicity and maximum tolerated dose	Continuous

Secondary Outcome Measures

Outcome Measure	Time Frame
RECIST criteria (version 1.0) for response evaluation by CT/MRI in target and non-target lesions of HCC	every 2 months
Repeat-dose pharmacokinetic behavior of GC33 and Sorafenib	Continuous

Collaborators and Investigators

• Sponsor: Chugai Pharmaceutical
• Collaborators: Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: September 9, 2009
• First Submitted That Met QC Criteria: September 11, 2009
• First Posted (Estimate): September 14, 2009

Study Record Updates

• Last Update Posted (Estimate): October 3, 2014
• Last Update Submitted That Met QC Criteria: October 1, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Advanced or metastatic HCC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: GC-002US