Trial of Sorafenib in Hepatocellular Cancer (HCC) Transplant Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00997022
Recruitment Status : Completed
First Posted : October 16, 2009
Last Update Posted : August 10, 2015
Information provided by (Responsible Party):
Columbia University

Brief Summary:
This Phase I study of sorafenib in high risk hepatocellular cancer patients after liver transplantation will study 24 subjects for about 5 years. Each subject will receive sorafenib for 6 months. Safety and effectiveness on the post transplant, high risk HCC patients will be studied.

Condition or disease Intervention/treatment Phase
Hepatocellular Cancer Drug: Sorafenib Phase 1

Detailed Description:

Sorafenib (BAY 43-9006) is an oral multi-kinase inhibitor with effects on tumor proliferation and angiogenesis. Sorafenib is approved for the treatment of patients with advanced renal cancer and unresectable hepatocellular carcinoma (HCC). The recommended daily dose of Sorafenib is 400 mg (2 x 200 mg tablets) taken twice daily without food (at least 1 hour before or 2 hours after a meal). Studies of single-agent sorafenib showed treatment was well-tolerated with manageable side effects. The results seen with sorafenib in the Phase III (SHARP) trial suggest that VEGF and RAF kinase inhibition prolong survival in patients with advanced HCC. It is not known whether a drug which is considered primarily cytostatic will be effective in preventing cancer recurrences in the setting of minimal residual disease.

This is a phase I, single center, open-label, dose-escalation study to determine the maximum tolerated dose (MTD) and overall safety profile of daily sorafenib as therapy to prevent HCC recurrence in liver transplant subjects with high-risk HCC. For each subject, the study will consist of two phases: a treatment phase and an extension phase.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Open-Label, Dose-Finding Study of BAY 43-9006 (Sorafenib) in High-risk Hepatocellular Cancer Patients After Liver Transplantation
Study Start Date : May 2009
Actual Primary Completion Date : May 2015
Actual Study Completion Date : May 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

Arm Intervention/treatment
Experimental: Sorafenib
Daily sorafenib taken orally
Drug: Sorafenib

Dose escalation:

Dose level 1: 200mg of sorafenib daily

Dose level 2: 200mg of sorafenib BID (twice daily)

Dose level 3: 200mg QAM (taken every morning) and 400mg QPM (taken every evening)

Dose level 4: 400mg BID (twice daily)

Other Name: Nexavar

Primary Outcome Measures :
  1. Maximum tolerated dose of daily sorafenib [ Time Frame: Every two weeks throughout six cycles ]

Secondary Outcome Measures :
  1. Duration of disease free survival [ Time Frame: Every three months for 2 years ]
  2. Duration of progression free survival [ Time Frame: Every three months for 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age ≥18 years old
  • ECOG Performance Status 0-2
  • Post liver transplant and have explants with histologically confirmed hepatocellular carcinoma.
  • No evidence of HCC disease at study entry by imaging
  • Eligible to start 4 weeks post transplant (29 days post transplant) as long as they are on stable doses of immunosuppressants.
  • "High risk" for recurrence after transplantation
  • Received prior surgical resection, chemoembolization or other local therapy prior to transplant.
  • Have Child-Pugh Class A or compensated Child-Pugh Class B liver dysfunction at the start of therapy
  • Have adequate bone marrow, liver and renal function as assessed by the following:

    • Hemoglobin ≥ 8.0 g/dl
    • Absolute neutrophil count (ANC) ≥ 1,500/mm3
    • Platelet count ≥ 75,000/mm3
    • Total bilirubin ≤ 1.5 times ULN
    • ALT and AST ≤ 5 x ULN
    • Creatinine ≤ 1.5 times ULN
    • Albumin ≥ 2.5 mg/dl
  • Women of childbearing potential must have a negative serum pregnancy test performed within 14 days prior to the start of treatment
  • Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least three months after the last administration of sorafenib.
  • Exhibit the ability to understand and willingness to sign a written informed consent regarding the study and alternative treatments.
  • INR < 1.5 or a PT/PTT within normal limits.

Exclusion Criteria:

  • Cardiac disease: Congestive heart failure > class II NYHA.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • Uncontrolled hypertension, defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
  • Active clinically serious infection > CTCAE Grade 2.
  • Thromboembolic events such as a cerebrovascular accident (including transient ischemic attacks) within the past 6 months.
  • Any hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug.
  • Serious non-healing wound, ulcer, or bone fracture within 4 weeks of first dose of study drug.
  • Evidence or history of bleeding diathesis or coagulopathy within 4 weeks of first dose of study drug.
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
  • Use of St. John's Wort or rifampin within 4 weeks of first dose of study drug.
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial.
  • Any condition that impairs patient's ability to swallow whole pills.
  • Patients who are pregnant or breastfeeding. Breastfeeding should be discontinued if the patient is to be treated.
  • Prior malignancy treated during the prior 5-years (other than localized non-melanoma carcinoma of the skin).
  • Any condition or social situation that may limit patient's compliance with the study regimen
  • Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis prior to enrollment.
  • Known human immunodeficiency virus (HIV) infection (hepatitis B and hepatitis C infection will not be exclusion criteria.
  • Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug.
  • Any malabsorption problem which in the investigator's opinion would prevent adequate absorption of the sorafenib.
  • On M-Tor inhibitors

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00997022

United States, California
University of Southern California
Los Angeles, California, United States, 90089
University of California, Los Angeles
Los Angeles, California, United States, 90095
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Principal Investigator: Abby Siegel, MD, MS Columbia University

Responsible Party: Columbia University Identifier: NCT00997022     History of Changes
Other Study ID Numbers: AAAD3519
First Posted: October 16, 2009    Key Record Dates
Last Update Posted: August 10, 2015
Last Verified: August 2015

Keywords provided by Columbia University:
High-risk Hepatocellular Cancer

Additional relevant MeSH terms:
Liver Neoplasms
Carcinoma, Hepatocellular
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs