Stereotactic Radiation Therapy and Sorafenib in the Treatment of Hepatocellular Carcinoma (RAD 0901)

RAD 0901- Stereotactic Radiation Therapy and Sorafenib in the Treatment of Hepatocellular Carcinoma

This study is to determine the safety and efficacy of stereotactic body radiotherapy (SBRT) and treatment drug in patients with hepatocellular carcinoma.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma; Liver Cancer
• Intervention / Treatment: Radiation: Stereotactic Body Radiotherapy (SBRT); Drug: Sorafenib

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiation followed by Sorafenib; Radiation therapy, stereotactic body radiation therapy followed by Sorafenib	Radiation: Stereotactic Body Radiotherapy (SBRT); SBRT; Drug: Sorafenib; Nexavar in bottles of 120 tables; Other Names: BAY 43-9006; Nexavar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	between baseline and 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	baseline, 4 weeks and 10 weeks
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.	baseline, 4 weeks and 10 weeks
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.	baseline, 4 weeks after baseline and 10 weeks post 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).	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.	baseline, 4 weeks post baseline, 10 weeks post baseline

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
• Investigators: Principal Investigator: Kimberly S Keene, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: October 30, 2009
• First Submitted That Met QC Criteria: October 30, 2009
• First Posted (Estimate): November 1, 2009

Study Record Updates

• Last Update Posted (Actual): May 10, 2017
• Last Update Submitted That Met QC Criteria: April 3, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: HCC; Hepatocellular carcinoma; Liver Cancer; adult primary hepatocellular carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: F090910004