Clinical trial NCT00976170: Study of GC33 and Sorafenib in Combination 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 in Combination With Sorafenib (Nexavar®) in Patients With Advanced or Metastatic Hepatocellular Carcinoma (HCC).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Keywords: Advanced or metastatic HCC
Lead sponsor: Chugai Pharmaceutical
Sponsor class: INDUSTRY
Collaborators: name: Hoffmann-La Roche
First posted: 2009-09-14
Enrollment: 42
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 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.

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.

Primary outcomes:
measure: Toxicity evaluation in accordance with CTCAE v3.0
timeFrame: Continuous
measure: Dose limiting toxicity and maximum tolerated dose
timeFrame: Continuous
Secondary outcomes:
measure: RECIST criteria (version 1.0) for response evaluation by CT/MRI in target and non-target lesions of HCC
timeFrame: every 2 months
measure: Repeat-dose pharmacokinetic behavior of GC33 and Sorafenib
timeFrame: Continuous
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan Univercity Hospital
Study officials:
References:
citation: 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.