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

This study has been terminated.
(Sponsor(Bayer)did not wish to continue with study due to slow accrual. Therefore, there is insufficient data and will not be any study results/outcomes.)
Sponsor:
Collaborator:
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Information provided by (Responsible Party):
Dr. Kimberly Keene, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT01005875
First received: October 30, 2009
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention
Hepatocellular Carcinoma
Liver Cancer
Drug: Sorafenib
Radiation: Stereotactic Body Radiotherapy (SBRT)

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: RAD 0901- Stereotactic Radiation Therapy and Sorafenib in the Treatment of Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Determine the Safety and Tolerability of Sequential SBRT and Sorafenib in Patients With Unresectable Hepatocellular Carcinoma [ Time Frame: between baseline and 3 years ] [ Designated as safety issue: Yes ]
    Number of subjects experiencing a Grade 5 toxicity related to SBRT and sorafenib


Secondary Outcome Measures:
  • 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 [ Time Frame: baseline, 4 weeks and 10 weeks ] [ Designated as safety issue: No ]
    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). [ Time Frame: baseline, 4 weeks and 10 weeks ] [ Designated as safety issue: No ]
    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. [ Time Frame: baseline, 4 weeks after baseline and 10 weeks post baseline ] [ Designated as safety issue: No ]
    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). [ Time Frame: baseline, 4 weeks post baseline, 10 weeks post baseline ] [ Designated as safety issue: No ]
    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.


Enrollment: 5
Study Start Date: November 2009
Study Completion Date: June 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Radiation followed by Sorafenib
Radiation therapy, stereotactic body radiation therapy followed by Sorafenib
Drug: Sorafenib
Nexavar in bottles of 120 tables
Other Names:
  • BAY 43-9006
  • Nexavar
Radiation: Stereotactic Body Radiotherapy (SBRT)
SBRT

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01005875

Locations
United States, Alabama
UAB
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
Investigators
Principal Investigator: Kimberly S Keene, MD University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: Dr. Kimberly Keene, Assistant Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT01005875     History of Changes
Other Study ID Numbers: F090910004
Study First Received: October 30, 2009
Results First Received: April 9, 2014
Last Updated: May 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
Hepatocellular carcinoma
HCC
Liver Cancer
adult primary hepatocellular carcinoma

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014