Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Bayer
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
Rebecca Miksad, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00813293
First received: December 22, 2008
Last updated: May 14, 2014
Last verified: May 2014
  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:


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 2014
Estimated Primary Completion Date: December 2014 (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
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
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Bayer
Onyx Therapeutics, Inc.
Investigators
Principal Investigator: Rebecca A Miksad, MD, MPH Beth Israel Deaconess Medical Center
  More Information

Publications:
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: May 14, 2014
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
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014