Hepatocellular Carcinoma, Liver Cancer
Conditions
Keywords
Hepatocellular carcinoma, HCC, Liver Cancer, adult primary hepatocellular carcinoma
Brief summary
This study is to determine the safety and efficacy of stereotactic body radiotherapy (SBRT) and treatment drug in patients with hepatocellular carcinoma.
Interventions
DRUGSorafenib
Nexavar in bottles of 120 tables
RADIATIONStereotactic Body Radiotherapy (SBRT)
SBRT
Sponsors
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Child-Pugh class A or B7 cirrhosis. * No prior radiation therapy to the upper right abdominal quadrant. * Size of each tumor less than 6 cm. * Three or less known lesions. * More than 800 cc of uninvolved liver. * Age \> 19 years old * ECOG Performance Status 0 or 1 * Adequate bone marrow, liver and renal function as assessed by the following: * Hemoglobin \> 8.5 g/dl * Platelet count \> 50,000/mm3 * Total bilirubin \< 1.5 times ULN * ALT and AST \< 2.5 times the ULN ( \< 5 x ULN for patients with liver involvement) * Creatinine \< 1.5 times ULN * Women of childbearing potential must have a negative serum pregnancy test performed within 7 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. * Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures. * INR \< 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
Exclusion criteria
* Child-Pugh class B8 or C cirrhosis. * ECOG greater than or equal to 2. * Uncontrolled ascites despite medical management. * Less than 800 cc of uninvolved liver. * Prior radiotherapy to the upper abdominal quadrant. * Prior antiangiogenic or tyrosine kinase inhibitor therapy Cardiac disease: Congestive heart failure \> class II NYHA. Patients must not have unstable angina(anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months. * Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis. * 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. * Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C. * Active clinically serious infection \> CTCAE Grade 2. * Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months. * Pulmonary hemorrhage/bleeding event \> CTCAE Grade 2 within 4 weeks of first dose of study drug. * Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks of first dose of study drug. * Serious non-healing wound, ulcer, or bone fracture. * Evidence or history of bleeding diathesis or coagulopathy * Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug. * Use of St. John's Wort or rifampin (rifampicin). * 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. * Any malabsorption problem. * Pregnant or lactating female.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Safety and Tolerability of Sequential SBRT and Sorafenib in Patients With Unresectable Hepatocellular Carcinoma | between baseline and 3 years | Number of subjects experiencing a Grade 5 toxicity related to SBRT and sorafenib |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Tumor Volume | baseline, 4 weeks and 10 weeks | mean tumor volume at baseline, 4 weeks and 10 weeks after start of treatment |
| The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Ktrans (Volume Transfer Coefficient). | baseline, 4 weeks and 10 weeks | The initial mean Ktrans at baseline, 4 weeks and 10 week. K trans is used to describe the uptake of gadolinium contrast in tissue. |
| The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Kep. Kep Describes How Fast Contrast Can Redistribute in Tissue. | baseline, 4 weeks after baseline and 10 weeks post baseline | The Kep as measures by MRI at baseline, 4 weeks after baseline, and 10 weeks after baseline. |
| The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by ADC (Apparent Diffusion Coefficient). | baseline, 4 weeks post baseline, 10 weeks post baseline | the measured ADC at baseline, 4 weeks after baseline and then 10 weeks after baseline. ADC quantifies the motion of water protons from an MRI. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiation Followed by Sorafenib Radiation therapy, stereotactic body radiation therapy followed by Sorafenib
Sorafenib: Nexavar in bottles of 120 tables
Stereotactic Body Radiotherapy (SBRT): SBRT | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 3 |
Baseline characteristics
| Characteristic | Radiation Followed by Sorafenib |
|---|---|
| Age, Continuous | 60 years |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 5 |
| other Total, other adverse events | 1 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
Determine the Safety and Tolerability of Sequential SBRT and Sorafenib in Patients With Unresectable Hepatocellular Carcinoma
Number of subjects experiencing a Grade 5 toxicity related to SBRT and sorafenib
Time frame: between baseline and 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Radiation Followed by Sorafenib | Determine the Safety and Tolerability of Sequential SBRT and Sorafenib in Patients With Unresectable Hepatocellular Carcinoma | 2 participants |
Secondary
The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by ADC (Apparent Diffusion Coefficient).
the measured ADC at baseline, 4 weeks after baseline and then 10 weeks after baseline. ADC quantifies the motion of water protons from an MRI.
Time frame: baseline, 4 weeks post baseline, 10 weeks post baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Radiation Followed by Sorafenib | The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by ADC (Apparent Diffusion Coefficient). | at baseline | 1.29 milimeters^2/sec | Standard Deviation 0.09 |
| Radiation Followed by Sorafenib | The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by ADC (Apparent Diffusion Coefficient). | at 4 weeks after baseline | 1.55 milimeters^2/sec | Standard Deviation 0.13 |
| Radiation Followed by Sorafenib | The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by ADC (Apparent Diffusion Coefficient). | at 10 weeks after baseline | 1.65 milimeters^2/sec | Standard Deviation 0.18 |
Secondary
The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Kep. Kep Describes How Fast Contrast Can Redistribute in Tissue.
The Kep as measures by MRI at baseline, 4 weeks after baseline, and 10 weeks after baseline.
Time frame: baseline, 4 weeks after baseline and 10 weeks post baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Radiation Followed by Sorafenib | The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Kep. Kep Describes How Fast Contrast Can Redistribute in Tissue. | at baseline | 0.062 Min^ -1 | Standard Deviation 0.018 |
| Radiation Followed by Sorafenib | The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Kep. Kep Describes How Fast Contrast Can Redistribute in Tissue. | at 4 weeks after baseline | 0.053 Min^ -1 | Standard Deviation 0.013 |
| Radiation Followed by Sorafenib | The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Kep. Kep Describes How Fast Contrast Can Redistribute in Tissue. | at 10 weeks after baseline | 0.050 Min^ -1 | Standard Deviation 0.014 |
Secondary
The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Ktrans (Volume Transfer Coefficient).
The initial mean Ktrans at baseline, 4 weeks and 10 week. K trans is used to describe the uptake of gadolinium contrast in tissue.
Time frame: baseline, 4 weeks and 10 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Radiation Followed by Sorafenib | The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Ktrans (Volume Transfer Coefficient). | at 4 weeks after baseline | 0.017 min^ -1 | Standard Deviation 0.009 |
| Radiation Followed by Sorafenib | The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Ktrans (Volume Transfer Coefficient). | at 10 weeks after baseline | 0.014 min^ -1 | Standard Deviation 0.006 |
| Radiation Followed by Sorafenib | The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Ktrans (Volume Transfer Coefficient). | at baseline | 0.022 min^ -1 | Standard Deviation 0.009 |
Secondary
The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Tumor Volume
mean tumor volume at baseline, 4 weeks and 10 weeks after start of treatment
Time frame: baseline, 4 weeks and 10 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Radiation Followed by Sorafenib | The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Tumor Volume | at baseline | 98 centimeters^3 | Standard Deviation 71 |
| Radiation Followed by Sorafenib | The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Tumor Volume | at 4 weeks after baseline | 65 centimeters^3 | Standard Deviation 42 |
| Radiation Followed by Sorafenib | The Degree of Change in Necrosis and Vascular Permeability Via Dynamic Contrast Enhanced (DCE) and Diffusion-weighted Imaging (DWI) Magnetic Resonance Imaging (MRI) as Measured by Tumor Volume | at 10 weeks after baseline | 22 centimeters^3 | Standard Deviation 8 |