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Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00813293
Recruitment Status : Completed
First Posted : December 23, 2008
Results First Posted : June 22, 2020
Last Update Posted : September 29, 2020
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Bayer
Onyx Therapeutics, Inc.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Andrea Bullock MD, MPH, Beth Israel Deaconess Medical Center

Brief Summary:
The purpose of this research study is to determine if sorafenib improves the effectiveness of a procedure called radiofrequency ablation (RFA) for the treatment of hepatocellular cancer (HCC). Radiofrequency ablation has been used to treat many types of tumors, including hepatocellular cancers. During RFA 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. Pre-clinical data suggests that sorafenib may improve the efficacy of RFA.

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

Detailed Description:

Hepatocellular cancer (HCC) has a poor prognosis with increasing mortality in the United States. Because HCC generally develops in patients with underlying liver disease, resection is often not possible. Liver transplant improves survival for HCC patients but given the national organ donor shortage often patients have to wait a considerable time for transplant. Liver-directed therapies such as radiofrequency ablation (RFA) remain important tools to control tumor growth and to potentially "bridge" patients to liver transplant. However, liver-directed therapies for HCC tumors greater than 3cm in size are suboptimal, leaving a critical unmet need.

Antiangiogenic systemic agents, such as oral sorafenib, reduce tumor blood flow and have been shown to improve RFA efficacy in animal and in computer models.

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Study Type : Interventional  (Clinical Trial)
Actual 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 : June 2009
Actual Primary Completion Date : November 2013
Actual Study Completion Date : November 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer
Drug Information available for: Sorafenib

Arm Intervention/treatment
Experimental: Sorafenib
Participants received a nine-day course of oral sorafenib 400 mg twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).
Drug: Sorafenib
Other Name: Nexavar

Procedure: radiofrequency ablation
Other Name: RFA

Placebo Comparator: Placebo
Participants received a nine-day course of placebo pills twice a day and radiofrequency ablation (RFA) on Day 10. Tumors in each group underwent RFA using a standard regimen (1 cm tip, 70 ± 2º C, 5 min).
Procedure: radiofrequency ablation
Other Name: RFA




Primary Outcome Measures :
  1. Coagulation Zone Diameter-Short Axis [ Time Frame: Up to day 50 from study enrollment (target 30 days after RFA) ]
    The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

  2. Coagulation Zone Diameter-Long Axis [ Time Frame: Up to day 50 from study enrollment (target 30 days after RFA) ]
    The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

  3. Coagulation Zone Volume [ Time Frame: Up to day 50 from study enrollment (target 30 days after RFA) ]
    The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.


Secondary Outcome Measures :
  1. Feasibility Rate [ Time Frame: Up to day 14 since enrollment ]
    Feasibility rate is defined as the percentage of participants completing radiofrequency ablation following 9 days of sorafenib or placebo therapy.

  2. Number of Treatment-Related Grade 1-4 Adverse Events (AEs) by Day 9 [ Time Frame: Day 9 ]
    AEs were assessed based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v3.0). The number of Grade 1-4 AEs with treatment attribution possibly, probably or definitely related up to day 9 of study drug treatment were counted for this outcome. Worst grade by patient within AE type was calculated. Participants could have multiple different AE types within a grade.

  3. Number of Treatment-Related Grade 1-4 Adverse Events (AEs) on Day of Radiofrequency Ablation (RFA) [ Time Frame: Up to day 14 (target day 10 RFA) ]
    AEs were assessed based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v3.0). The number of Grade 1-4 AEs with treatment attribution possibly, probably or definitely related on day of RFA treatment were counted for this outcome. Worst grade by patient within AE type was calculated. Participants could have multiple AE types within a grade.

  4. Number of Treatment-Related Grade 1-4 Adverse Events (AEs) One Month After Radiofrequency Ablation (RFA) [ Time Frame: Up to day 40 post RFA (target 30 days) ]
    AEs were assessed based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v3.0). The number of Grade 1-4 AEs with treatment attribution possibly, probably or definitely related one month after RFA treatment were counted for this outcome. Worst grade by patient within AE type was calculated. Participants could have multiple AE types within a grade.



Information from the National Library of Medicine

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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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00813293


Locations
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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
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Bayer
Onyx Therapeutics, Inc.
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Andrea Bullock, MD, MPH Beth Israel Deaconess Medical Center
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Andrea Bullock MD, MPH, Principal Investigator, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT00813293    
Other Study ID Numbers: 08-256
K23CA139005 ( U.S. NIH Grant/Contract )
IST000508 ( Other Grant/Funding Number: Bayer/Onyx )
First Posted: December 23, 2008    Key Record Dates
Results First Posted: June 22, 2020
Last Update Posted: September 29, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Andrea Bullock MD, MPH, Beth Israel Deaconess Medical Center:
Hepatocellular Cancer
HCC
Liver Cancer
radiofrequency ablation
RFA
sorafenib
nexavaar
liver directed therapy
interventional radiology
Additional relevant MeSH terms:
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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
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action