Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Hepatocellular Cancer	Drug: Sorafenib; Procedure: radiofrequency ablation	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	20 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, 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
Actual Study Start Date :	January 2009
Actual Primary Completion Date :	December 2016
Estimated Study Completion Date :	December 2017

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Intervention Arm; Sorafenib treatment given prior to radiofrequency ablation	Drug: Sorafenib; Short course of sorafenib given orally twice a day prior to RFA; Other Name: Nexavar; Procedure: radiofrequency ablation; all patients receive standard of care radiofrequency ablation
Placebo Comparator: Placebo Arm; Placebo pills given prior to radiofrequency ablation	Procedure: radiofrequency ablation; all patients receive standard of care radiofrequency ablation

Outcome Measures

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Primary Outcome Measures :

1. To prospectively investigate if sorafenib increases the effectiveness of RFA. [ Time Frame: 2 years ]
   Difference in volume and diameter of coagulation zone

Secondary Outcome Measures :

1. To describe the safety and feasibility of sorafenib prior to RFA. [ Time Frame: 2 years ]
2. To explore the relationship between MRI and RFA effectiveness [ Time Frame: 2 years ]
3. To investigate tumor tissue for changes after sorafenib and to assess for RFA predictors [ Time Frame: 3 years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
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

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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

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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 ( U.S. NIH Grant/Contract ); IST000508 ( Other Grant/Funding Number: Bayer/Onyx )
First Posted:	December 23, 2008
Last Update Posted:	February 27, 2017
Last Verified:	February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Studies a U.S. FDA-regulated Drug Product:		No
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Rebecca Miksad, MD, MPH, 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; Carcinoma, Hepatocellular; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type	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