Recruitment

Recruitment Status
Active, not recruiting

Inclusion Criteria

Hemoglobin >= 8.5 g/dL
Patients must be enrolled between 6 to 12 weeks post OLT
Serum creatinine < 2 x the upper limit of normal
...
Hemoglobin >= 8.5 g/dL
Patients must be enrolled between 6 to 12 weeks post OLT
Serum creatinine < 2 x the upper limit of normal
Cadaveric donors only (no living donor liver transplantation [LDLT] or donor after cardiac death transplantation [DCDT])
Platelet count > 50 x 10^9/L
PIVKA > 400 (pre-transplant)
Patients with a life expectancy > 12 weeks
AFP > 500 (pre-transplant)
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
Patients (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form (ICF) until at least 30 days after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate
Patient must be able to swallow and retain oral medication
Amylase and lipase =< 1.5 x the upper limit of normal
Total bilirubin =< 5 mg/dL
Patients must have completed prednisone taper within 6 weeks post OLT
Patient must exhibit the ability to understand and willingness to sign a written informed consent regarding the study and alternative treatments
Alanine transaminase (ALT) and aspartate aminotransferase (AST) =< 5 x upper limit of normal
No sorafenib prior to inclusion in the study
Prothrombin time (PT) =< 6 seconds or international normalized ratio (INR) =< 2.3

Exclusion Criteria

Autologous bone marrow transplant or stem cell rescue within four months of start of study drug
Low dose aspirin (=< 100 mg daily).
Prior use of raf-kinase inhibitors (sorafenib), VEGF inhibitors, MEK inhibitors or farnesyl transferase inhibitors
...
Autologous bone marrow transplant or stem cell rescue within four months of start of study drug
Low dose aspirin (=< 100 mg daily).
Prior use of raf-kinase inhibitors (sorafenib), VEGF inhibitors, MEK inhibitors or farnesyl transferase inhibitors
Coronary artery disease
Patients using cytochrome P450 3A4 (CYP3A4) inducers (eg, phenytoin, carbamazepine, phenobarbital, St. John's Wort dexamethasone) at a dose of greater than 16 mg daily, or rifampin and/or rifabutin within 28 days before randomization
Use of alemtuzumab
Concomitant oral mTOR inhibitor treatment
Concomitant treatment with rifampin and St. John's wort
Prior use of raf-kinase inhibitors (sorafenib), vascular endothelial growth factor (VEGF) inhibitors, mitogen-activated protein kinase (MAPK)/extracellular-signal-related kinase (ERK) kinase (MEK) inhibitors, or farnesyl transferase inhibitors
Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial
Use of alemtuzumab
Presence of a non-healing wound, non-healing ulcer, or bone fracture
Requirement of re-transplantation for primary non function
Heparins and heparinoids Use of any other investigational drug
Any condition which, in the investigator's opinion, makes the patient unsuitable for trial participation
Prior use of any systemic chemotherapy for HCC
Congestive heart failure - New York Heart Association (NYHA) > class II
Use of T-cell depleting agents
Evidence or history of bleeding diathesis or coagulopathy
Use of biologic response modifiers, such as granulocyte colony-stimulating factor (G-CSF), will not be permitted within 3 weeks prior to study entry; G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity, such as febrile neutropenia, when clinically indicated or at the discretion of the investigator; however, they may not be administered to prevent a dose reduction; patients taking chronic erythropoietin are permitted, provided no dose adjustment is undertaken within 1 month prior to randomization or during the study
Patients with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks [TIAs]) within 6 months before randomization
Clinically active serious infection documented by positive cultures or an incomplete course of treatment for bacteremia or fungemia
Women who are pregnant or breast-feeding
Use of direct acting antivirals for HCV recurrence
Patients with fibrolamellar HCC, cholangiocarcinoma, and combined HCC-cholangiocarcinoma
Use of direct acting antivirals for HCV recurrence
Human immunodeficiency virus (HIV) positive patients
100% tumor necrosis on explant pathology
Patient with documented evidence of metastatic disease
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
Hepatitis C virus (HCV) recurrence at the time of randomization
Living donor liver transplant (LDLT) or donation after cardiac death transplant (DCDT)
Prior use of systemic investigational agents for HCC
Uncontrolled hypertension, defined as systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management
Any malabsorption condition
Patients with any pulmonary hemorrhage/bleeding event grade 2 or higher within 4 weeks before randomization
Use of mammalian target of rapamycin (mTOR) inhibitors prior to transplant and as post-transplant immunosuppression
Inability to comply with the protocol and/or not willing or not available for follow-up assessments
Patients with non-HCC malignancy except those with DCIS (ductal carcinoma in situ), cervical cancer in-situ, basal cell or superficial bladder tumor; patients surviving a cancer that was curatively treated and without evidence of recurrence for more than 3 years before randomization are allowed
Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
Unstable angina or new-onset angina within 3 months before randomization, or myocardial infarction (MI) within 6 months before randomization

Summary

Conditions
  • Adult Primary Hepatocellular Carcinoma
  • Localized Resectable Adult Primary Liver Cancer
  • Localized Unresectable Adult Primary Liver Cancer
  • Recurrent Adult Primary Liver Cancer
Type
Interventional
Phase
Phase 2
Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: Single (Participant)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 19 years and 125 years
Gender
Both males and females

Description

PRIMARY OBJECTIVES: I. Two-year recurrence free survival (RFS). SECONDARY OBJECTIVES: I. One-year recurrence free survival. II. Overall survival (OS). III. Safety. IV. Impact of drug-drug interactions (i.e. immunosuppression agents). V. Impact of biomarkers (alpha-fetoprotein [AFP], protein-induced ...

PRIMARY OBJECTIVES: I. Two-year recurrence free survival (RFS). SECONDARY OBJECTIVES: I. One-year recurrence free survival. II. Overall survival (OS). III. Safety. IV. Impact of drug-drug interactions (i.e. immunosuppression agents). V. Impact of biomarkers (alpha-fetoprotein [AFP], protein-induced by vitamin K absence or antagonist II [PIVKA II]). VI. Effects of therapy on wound healing. VII. Impact of hepatitis C viral recurrence. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive sorafenib tosylate orally (PO) twice daily (BID). ARM II: Patients receive placebo PO BID. In both arms treatment continues for 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 2 years.

Inclusion Criteria

Hemoglobin >= 8.5 g/dL
Patients must be enrolled between 6 to 12 weeks post OLT
Serum creatinine < 2 x the upper limit of normal
...
Hemoglobin >= 8.5 g/dL
Patients must be enrolled between 6 to 12 weeks post OLT
Serum creatinine < 2 x the upper limit of normal
Cadaveric donors only (no living donor liver transplantation [LDLT] or donor after cardiac death transplantation [DCDT])
Platelet count > 50 x 10^9/L
PIVKA > 400 (pre-transplant)
Patients with a life expectancy > 12 weeks
AFP > 500 (pre-transplant)
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
Patients (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form (ICF) until at least 30 days after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate
Patient must be able to swallow and retain oral medication
Amylase and lipase =< 1.5 x the upper limit of normal
Total bilirubin =< 5 mg/dL
Patients must have completed prednisone taper within 6 weeks post OLT
Patient must exhibit the ability to understand and willingness to sign a written informed consent regarding the study and alternative treatments
Alanine transaminase (ALT) and aspartate aminotransferase (AST) =< 5 x upper limit of normal
No sorafenib prior to inclusion in the study
Prothrombin time (PT) =< 6 seconds or international normalized ratio (INR) =< 2.3

Exclusion Criteria

Autologous bone marrow transplant or stem cell rescue within four months of start of study drug
Low dose aspirin (=< 100 mg daily).
Prior use of raf-kinase inhibitors (sorafenib), VEGF inhibitors, MEK inhibitors or farnesyl transferase inhibitors
...
Autologous bone marrow transplant or stem cell rescue within four months of start of study drug
Low dose aspirin (=< 100 mg daily).
Prior use of raf-kinase inhibitors (sorafenib), VEGF inhibitors, MEK inhibitors or farnesyl transferase inhibitors
Coronary artery disease
Patients using cytochrome P450 3A4 (CYP3A4) inducers (eg, phenytoin, carbamazepine, phenobarbital, St. John's Wort dexamethasone) at a dose of greater than 16 mg daily, or rifampin and/or rifabutin within 28 days before randomization
Use of alemtuzumab
Concomitant oral mTOR inhibitor treatment
Concomitant treatment with rifampin and St. John's wort
Prior use of raf-kinase inhibitors (sorafenib), vascular endothelial growth factor (VEGF) inhibitors, mitogen-activated protein kinase (MAPK)/extracellular-signal-related kinase (ERK) kinase (MEK) inhibitors, or farnesyl transferase inhibitors
Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial
Use of alemtuzumab
Presence of a non-healing wound, non-healing ulcer, or bone fracture
Requirement of re-transplantation for primary non function
Heparins and heparinoids Use of any other investigational drug
Any condition which, in the investigator's opinion, makes the patient unsuitable for trial participation
Prior use of any systemic chemotherapy for HCC
Congestive heart failure - New York Heart Association (NYHA) > class II
Use of T-cell depleting agents
Evidence or history of bleeding diathesis or coagulopathy
Use of biologic response modifiers, such as granulocyte colony-stimulating factor (G-CSF), will not be permitted within 3 weeks prior to study entry; G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity, such as febrile neutropenia, when clinically indicated or at the discretion of the investigator; however, they may not be administered to prevent a dose reduction; patients taking chronic erythropoietin are permitted, provided no dose adjustment is undertaken within 1 month prior to randomization or during the study
Patients with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks [TIAs]) within 6 months before randomization
Clinically active serious infection documented by positive cultures or an incomplete course of treatment for bacteremia or fungemia
Women who are pregnant or breast-feeding
Use of direct acting antivirals for HCV recurrence
Patients with fibrolamellar HCC, cholangiocarcinoma, and combined HCC-cholangiocarcinoma
Use of direct acting antivirals for HCV recurrence
Human immunodeficiency virus (HIV) positive patients
100% tumor necrosis on explant pathology
Patient with documented evidence of metastatic disease
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
Hepatitis C virus (HCV) recurrence at the time of randomization
Living donor liver transplant (LDLT) or donation after cardiac death transplant (DCDT)
Prior use of systemic investigational agents for HCC
Uncontrolled hypertension, defined as systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management
Any malabsorption condition
Patients with any pulmonary hemorrhage/bleeding event grade 2 or higher within 4 weeks before randomization
Use of mammalian target of rapamycin (mTOR) inhibitors prior to transplant and as post-transplant immunosuppression
Inability to comply with the protocol and/or not willing or not available for follow-up assessments
Patients with non-HCC malignancy except those with DCIS (ductal carcinoma in situ), cervical cancer in-situ, basal cell or superficial bladder tumor; patients surviving a cancer that was curatively treated and without evidence of recurrence for more than 3 years before randomization are allowed
Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
Unstable angina or new-onset angina within 3 months before randomization, or myocardial infarction (MI) within 6 months before randomization

Locations

Pittsburgh, Pennsylvania, 15213
Houston, Texas, 77030
Cherry Hill, New Jersey, 08034
Oklahoma City, Oklahoma, 73112
Ann Arbor, Michigan, 48109
...
Pittsburgh, Pennsylvania, 15213
Houston, Texas, 77030
Cherry Hill, New Jersey, 08034
Oklahoma City, Oklahoma, 73112
Ann Arbor, Michigan, 48109
New York, New York, 10016
Burlington, Massachusetts, 01805
Birmingham, Alabama, 35294-0007
Atlanta, Georgia, 30322
Washington, District of Columbia, 20057
Cleveland, Ohio, 44195
Hartford, Connecticut, 06112
New York, New York, 10065
Chicago, Illinois, 60611
New Orleans, Louisiana, 70121
Los Angeles, California, 90095
Baltimore, Maryland, 21287-8936
Houston, Texas, 77030
Omaha, Nebraska, 68198-7830
Denver, Colorado, 80217-3364
Nashville, Tennessee, 37232

Tracking Information

NCT #
NCT01624285
Collaborators
Bayer
Investigators
  • Principal Investigator: Ronald Busuttil Jonsson Comprehensive Cancer Center
  • Ronald Busuttil Jonsson Comprehensive Cancer Center