Stereotactic Radiation Therapy and Sorafenib in the Treatment of Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

— RAD 0901  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01005875
• Other study ID #: F090910004
• Status: Terminated
• Phase: N/A
• First received: October 30, 2009
• Last updated: May 12, 2014
• Start date: November 2009
• Est. completion date: June 2013

Study information

• Verified date: May 2014
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: June 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Liver Cancer
• Liver Neoplasms

Intervention

Drug:
• Sorafenib
Nexavar in bottles of 120 tables

Radiation:
• Stereotactic Body Radiotherapy (SBRT)
SBRT

Locations

Country	Name	City	State
United States	UAB	Birmingham	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	between baseline and 3 years	Yes
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	baseline, 4 weeks and 10 weeks	No
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.	baseline, 4 weeks and 10 weeks	No
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.	baseline, 4 weeks after baseline and 10 weeks post baseline	No
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.	baseline, 4 weeks post baseline, 10 weeks post baseline	No