Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer - Full Text View

Purpose

The purpose of this research study is to determine if sorafenib improves the effectiveness of a procedure called radiofrequency ablation for the treatment of hepatocellular cancer. During radiofrequency ablation (RF ablation) a needle is inserted into the tumor tissue and heat is used to kill the tumor cells.

Sorafenib has been approved by the FDA for the treatment of hepatocellular cancer that cannot be treated with surgery. Radiofrequency ablation has been used to treat many types of tumors, including hepatocellular cancers. Pre-clinical data suggests that sorafenib may improve the efficacy of RFA. The use of sorafenib prior to RF ablation in this study is "investigational" and has not been approved by the FDA. "Investigational" means that this combination is still being studied and that research doctors are trying to find out more about it. In this study, the study doctors hope to better understand the extent to which the combination of sorafenib and RFA may be done practically and successfully. Correlative imaging and tumor studies will evaluate mechanisms of action as well as novel predictors of RFA efficacy.

Condition	Intervention	Phase
Hepatocellular Cancer	Drug: Sorafenib Procedure: Radiofrequency Ablation	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Randomized, Double-Blind, Placebo-Controlled, Phase II Trial Of Short Course Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized (3.5 to 7cm) Hepatocellular Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Liver Cancer

Drug Information available for: Sorafenib Sorafenib tosylate

Genetic and Rare Diseases Information Center resources: Liver Cancer

U.S. FDA Resources

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:

To prospectively investigate if sorafenib increases the effectiveness of RFA. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Difference in volume and diameter of coagulation zone
To prospectively describe the effects of sorafenib on RFA treatment parameters [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To describe the safety and feasibility of sorafenib prior to RFA. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
To explore the relationship between MRI and RFA effectiveness [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To investigate tumor tissue for changes after sorafenib and to assess for RFA predictors [ Time Frame: 3 years ] [ Designated as safety issue: No ]


Estimated Enrollment:	20
Study Start Date:	January 2009
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Intervention Arm Sorafenib treatment given prior to RFA	Drug: Sorafenib Short course of sorafenib given orally twice a day prior to RFA Other Name: Nexavar Procedure: Radiofrequency Ablation Radiofrequency ablation to tumor. Repeat sessions allowed for full tumor treatment. Other Name: RFA
Placebo Comparator: Placebo Arm Placebo pills given prior to RFA	Procedure: Radiofrequency Ablation Radiofrequency ablation to tumor. Repeat sessions allowed for full tumor treatment. Other Name: RFA

Detailed Description:

Participants will be randomized to receive either sorafenib or placebo (pills with no medication). Participants will take sorafenib or placebo on Days 1-9. Radiofrequency ablation will be performed by an interventional radiologists on Day 10.

On Days 1 and 9 of the study participants will have a physical exam and blood tests performed. A study MRI will be performed at Beth Israel Deaconess Medical Center (BIDMC) prior to starting study medication and on Day 9. A tumor biopsy will be obtained at the time of RFA. A CT scan will be performed after RFA.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Confirmed hepatocellular cancer (HCC) by pathology or by NCCN imaging guidelines
All HCC stages are allowed. May be a liver transplant candidate.
At least one tumor (index tumor) accurately measured as 3.5-7cm in diameter (long and short axis diameter to be recorded, but only one needs to meet this criteria) on baseline imaging.
No prior therapy for the index tumor
No prior systemic treatment for HCC within 4 weeks and no prior anti-VEGF therapy within 8 weeks of study entry.
Life expectancy > 8 weeks.
ECOG >=0 or 1
RFA clinically indicated for index tumor.
Acceptable overall RFA and anesthesia risk.
Adequate bone marrow, liver and renal function: Hemoglobin >9.0 g/dl; Absolute neutrophil count (ANC)>1,500/mm3; Platelet count correctable to >50,000/mm3; compensated liver function (Child-Turcotte-Pugh A, B7 or B8); Creatinine <1.5 times ULN; INR correctable to <1.5.
Ability to take oral medication and no evidence of impaired absorption.

Exclusion Criteria

Urgent treatment of the index tumor anticipated.
Participants who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Participants currently receiving any other study agents.
Known brain metastases
History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib.
Participants receiving medications or substances that are inducers of CYP3A4 (rifampicin, St. John's wort, phenytoin, carbamazepine, phenobarbital and dexamethasone) or that are metabolized/eliminated by predominantly UGT1A1 pathway or by CYP2B6 and CYP2C8.
Decompensated liver disease
Uncontrolled hypertension
Thrombolic or embolic events within the past 6 months.
Hemorrhage/bleeding event within 4 weeks
Serious non-healing wound, ulcer, or bone fracture.
Evidence of severe or uncorrectable bleeding diathesis or coagulopathy
Major surgery, open biopsy or significant traumatic injury within 4 weeks of study entry.
Contraindication to or inability to undergo the RFA procedure,
Contraindication to or inability to undergo imaging with MRI
Uncontrolled intercurrent illness
Individuals with a history of a different malignancy unless disease-free for at least 5 years and are deemed by the Investigator to be at low risk for recurrence. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
HIV-positive individuals on combination antiretroviral therapy

For additional inclusion/exclusion criteria details contact Study Site.

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: NCT00813293

Locations


United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

Dana-Farber Cancer Institute

Brigham and Women's Hospital

Bayer

Onyx Therapeutics, Inc.

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Rebecca A Miksad, MD, MPH	Beth Israel Deaconess Medical Center

More Information

Publications:

Hakimé A, Hines-Peralta A, Peddi H, Atkins MB, Sukhatme VP, Signoretti S, Regan M, Goldberg SN. Combination of radiofrequency ablation with antiangiogenic therapy for tumor ablation efficacy: study in mice. Radiology. 2007 Aug;244(2):464-70.


Responsible Party:	Rebecca Miksad, MD, MPH, Assistant Professor, Harvard University; Attending Physician, Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00813293 History of Changes
Other Study ID Numbers:	08-256 K23CA139005 IST000508
Study First Received:	December 22, 2008
Last Updated:	March 24, 2016
Health Authority:	United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:


Hepatocellular Cancer HCC Liver Cancer radiofrequency ablation RFA	sorafenib nexavaar liver directed therapy interventional radiology

Additional relevant MeSH terms:


Liver Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Liver Diseases Sorafenib Niacinamide Antineoplastic Agents	Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Vitamin B Complex Vitamins Micronutrients Growth Substances Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 27, 2016