Sorafenib Tosylate Following a Liver Transplant in Treating Patients With Liver Cancer
A Phase II Randomized Multicenter Placebo-Controlled Blinded Study of Sorafenib Adjuvant Therapy in High Risk Orthotopic Liver Transplant (OLT) Recipients With Hepatocellular Carcinoma (HCC)
2 other identifiers
interventional
20
1 country
21
Brief Summary
The purpose of this study is to determine if sorafenib (sorafenib tosylate) is a safe and effective treatment option for preventing liver cancer in high risk patients following liver transplantation. Liver transplantation is a treatment option for liver cancer patients, but despite transplantation, the liver cancer can recur in the new, transplanted liver. It is not known whether sorafenib is effective in preventing cancer recurrence in high risk patients following liver transplantation
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jul 2012
Longer than P75 for phase_2
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 18, 2012
CompletedFirst Posted
Study publicly available on registry
June 20, 2012
CompletedStudy Start
First participant enrolled
July 16, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2023
CompletedDecember 14, 2023
February 1, 2023
10.6 years
June 18, 2012
December 8, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Recurrence-free survival, evaluated using the new international criteria proposed by the Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Committee
Estimated using the Kaplan-Meier method. Compared between the drug verses placebo groups using the unstratified log rank test. Hazard rates, hazard rate ratios and median times to recurrence (or 25 percentiles if median time is not reached) and their corresponding 95% confidence bounds will be reported. A secondary analysis will also be presented stratified by macro versus non-macro status, the most important potential covariate.
Defined as the time from randomization to the first documented disease recurrence by radiological assessment or death due to any cause whichever occurs first, assessed at 2 years
Secondary Outcomes (7)
Overall survival
From randomization to the date of death or the last date the subject was known to be alive, assessed up to 2 years after completion of study treatment
Recurrence-free survival, evaluated using the new international criteria proposed by the mRECIST Committee
Defined as the time from randomization to the first documented disease recurrence by radiological assessment or death due to any cause whichever occurs first, assessed at 1 year
Adverse events assessed in terms of seriousness, severity, and relationship to the study material according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Assessed up to 2 years
Impact of drug-drug interactions
Assessed up to 2 years after completion of study treatment
Impact of biomarkers (AFP and PIVKA II)
Assessed up to 2 years after completion of study treatment
- +2 more secondary outcomes
Study Arms (2)
Arm I (sorafenib tosylate)
EXPERIMENTALPatients receive sorafenib tosylate PO BID.
Arm II (placebo)
PLACEBO COMPARATORPatients receive placebo PO BID.
Interventions
Given PO
Eligibility Criteria
You may qualify if:
- Patients must have hepatocellular carcinoma (HCC) with one of the following on explant: microvascular/macrovascular invasion, tumor outside of Milan criteria, poor tumor differentiation; patients with macrovascular invasion on explant pathology will be stratified
- \* Additionally, the following will be included
- \*\* Patients with elevated surrogate markers (AFP \> 500 or PIVKA \> 400) pre transplant and with biopsy proven HCC prior to orthotopic liver transplantation (OLT) or on explant
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
- Patients with a life expectancy \> 12 weeks
- Patients must have completed prednisone taper within 6 weeks post OLT
- Patients must be enrolled between 6 to 12 weeks post OLT
- Cadaveric donors only (no living donor liver transplantation \[LDLT\] or donor after cardiac death transplantation \[DCDT\])
- Platelet count \> 50 x 10\^9/L
- Hemoglobin \>= 8.5 g/dL
- Total bilirubin =\< 5 mg/dL
- Alanine transaminase (ALT) and aspartate aminotransferase (AST) =\< 5 x upper limit of normal
- Amylase and lipase =\< 1.5 x the upper limit of normal
- Serum creatinine \< 2 x the upper limit of normal
- Prothrombin time (PT) =\< 6 seconds or international normalized ratio (INR) =\< 2.3
- +8 more criteria
You may not qualify if:
- Significant ongoing immunologic rejection based on pathology and clinical diagnosis (from time of transplant until randomization)
- Use of T cell depleting agents for prevention or treatment of rejection at any point prior to or after enrollment in the study
- Patient with documented evidence of metastatic disease
- % tumor necrosis on explant pathology
- Use of mammalian target of rapamycin (mTOR) inhibitors prior to transplant and as post-transplant immunosuppression
- Use of alemtuzumab
- Living donor liver transplant (LDLT) or donation after cardiac death transplant (DCDT)
- Human immunodeficiency virus (HIV) positive patients
- Hepatitis C virus (HCV) recurrence at the time of randomization
- Use of direct acting antivirals for HCV recurrence
- Requirement of re-transplantation for primary non function
- Uncontrolled hypertension, defined as systolic blood pressure \> 140 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management
- Active or clinically significant cardiac disease including:
- Congestive heart failure - New York Heart Association (NYHA) \> class II
- Coronary artery disease
- +31 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Jonsson Comprehensive Cancer Centerlead
- Bayercollaborator
Study Sites (21)
University of Alabama
Birmingham, Alabama, 35294-0007, United States
Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095, United States
University of Colorado
Denver, Colorado, 80217-3364, United States
Mount Sinai Hospital
Hartford, Connecticut, 06112, United States
Lombardi Comprehensive Cancer Center at Georgetown University
Washington D.C., District of Columbia, 20057, United States
Emory University
Atlanta, Georgia, 30322, United States
Northwestern University
Chicago, Illinois, 60611, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121, United States
Johns Hopkins University
Baltimore, Maryland, 21287-8936, United States
Lahey Clinic Medical Center
Burlington, Massachusetts, 01805, United States
University of Michigan University Hospital
Ann Arbor, Michigan, 48109, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198-7830, United States
University of Pennsylvania Health System
Cherry Hill, New Jersey, 08034, United States
New York University Langone Medical Center
New York, New York, 10016, United States
New York Presbyterian-The University Hospital of Columbia and Cornell
New York, New York, 10065, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Integris-Baptist Medical
Oklahoma City, Oklahoma, 73112, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
Vanderbilt University
Nashville, Tennessee, 37232, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
The Methodist Hospital Research Institute
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ronald Busuttil
Jonsson Comprehensive Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 18, 2012
First Posted
June 20, 2012
Study Start
July 16, 2012
Primary Completion
February 1, 2023
Study Completion
February 1, 2023
Last Updated
December 14, 2023
Record last verified: 2023-02