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CompletedNCT00813293Updated Jun 13, 2023Results posted

Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer

A Phase 2 interventional study of Sorafenib and radiofrequency ablation in Hepatocellular Cancer, sponsored by Beth Israel Deaconess Medical Center. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-06-13.

Sponsored by Beth Israel Deaconess Medical Center · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
20
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Hepatocellular Cancer

Keywords

  • Hepatocellular Cancer
  • HCC
  • Liver Cancer
  • radiofrequency ablation
  • RFA
  • sorafenib
  • nexavaar
  • liver directed therapy
  • interventional radiology
03

In context

Liver Neoplasms

1,390 studies on the registry are indexed under Liver Neoplasms; 345 are open to participants now.

This study's enrollment of 20 is below the median of 47 across 967 interventional studies indexed under Liver Neoplasms.

Browse Liver Neoplasms studies →

Lead sponsor

Beth Israel Deaconess Medical Center is the lead sponsor of 560 studies on the registry; 80 are open to participants now.

Of its 75 completed or terminated interventional studies of FDA-regulated products, 61 (81%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
20 participants (actual)

Study arms

  • 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 · Procedure: radiofrequency ablation

  • 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

Interventions

  • DrugSorafenib

    Also known as: Nexavar

  • Procedureradiofrequency ablation

    Also known as: RFA

06

What researchers measure

Primary outcomes

  1. Coagulation Zone Diameter-Short Axis

    The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

    Time frame: Up to day 50 from study enrollment (target 30 days after RFA)

  2. Coagulation Zone Diameter-Long Axis

    The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

    Time frame: Up to day 50 from study enrollment (target 30 days after RFA)

  3. Coagulation Zone Volume

    The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

    Time frame: Up to day 50 from study enrollment (target 30 days after RFA)

Secondary outcomes

  1. Feasibility Rate

    Feasibility rate is defined as the percentage of participants completing radiofrequency ablation following 9 days of sorafenib or placebo therapy.

    Time frame: Up to day 14 since enrollment

  2. Number of Treatment-Related Grade 1-4 Adverse Events (AEs) by 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.

    Time frame: Day 9

  3. Number of Treatment-Related Grade 1-4 Adverse Events (AEs) on Day of Radiofrequency Ablation (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.

    Time frame: Up to day 14 (target day 10 RFA)

  4. Number of Treatment-Related Grade 1-4 Adverse Events (AEs) One Month After Radiofrequency Ablation (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 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.

    Time frame: Up to day 40 post RFA (target 30 days)

07

Results

Posted Jun 22, 2020
Limitations and caveats
This study is limited by small sample size.

Participant flow

Participants enrolled from June 2009 through August 2013.

Participant flow — Overall Study
MilestoneSorafenibPlacebo
Started1010
Started treatment910
Evaluable rfa78
Completed99
Not completed11
Withdrew: Intercurrent illness10
Withdrew: Adverse event01

Outcome measures

PrimaryCoagulation Zone Diameter-Short Axis

The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

Time frame:
Up to day 50 from study enrollment (target 30 days after RFA)
Reported as:
Mean · millimeters
Coagulation Zone Diameter-Short Axis
millimetersSorafenibPlacebo
Coagulation Zone Diameter-Short Axis36.0 ± 7.835.1 ± 8.8
PrimaryCoagulation Zone Diameter-Long Axis

The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

Time frame:
Up to day 50 from study enrollment (target 30 days after RFA)
Reported as:
Mean · millimeters
Coagulation Zone Diameter-Long Axis
millimetersSorafenibPlacebo
Coagulation Zone Diameter-Long Axis42.4 ± 9.244.1 ± 7.8
PrimaryCoagulation Zone Volume

The size of the coagulation zone was determined on CT imaging obtained after RFA for the single index tumor.

Time frame:
Up to day 50 from study enrollment (target 30 days after RFA)
Reported as:
Mean · centimeters^3
Coagulation Zone Volume
centimeters^3SorafenibPlacebo
Coagulation Zone Volume30.7 ± 24.630.5 ± 21.5
Statistical analysis
  • Sorafenib vs Placebo · Wilcoxon (Mann-Whitney) · p = .794
SecondaryFeasibility Rate

Feasibility rate is defined as the percentage of participants completing radiofrequency ablation following 9 days of sorafenib or placebo therapy.

Time frame:
Up to day 14 since enrollment
Reported as:
Number · percentage of particpants
Feasibility Rate
percentage of particpantsSorafenibPlacebo
Feasibility Rate90 (60.6 to 99.5)90 (60.6 to 99.5)
SecondaryNumber of Treatment-Related Grade 1-4 Adverse Events (AEs) by 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.

Time frame:
Day 9
Reported as:
Number · adverse events
Number of Treatment-Related Grade 1-4 Adverse Events (AEs) by Day 9
adverse eventsSorafenibPlacebo
Number of Treatment-Related Grade 1-4 Adverse Events (AEs) by Day 984
SecondaryNumber of Treatment-Related Grade 1-4 Adverse Events (AEs) on Day of Radiofrequency Ablation (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.

Time frame:
Up to day 14 (target day 10 RFA)
Reported as:
Number · adverse events
Number of Treatment-Related Grade 1-4 Adverse Events (AEs) on Day of Radiofrequency Ablation (RFA)
adverse eventsSorafenibPlacebo
Number of Treatment-Related Grade 1-4 Adverse Events (AEs) on Day of Radiofrequency Ablation (RFA)54
SecondaryNumber of Treatment-Related Grade 1-4 Adverse Events (AEs) One Month After Radiofrequency Ablation (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 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.

Time frame:
Up to day 40 post RFA (target 30 days)
Reported as:
Number · adverse events
Number of Treatment-Related Grade 1-4 Adverse Events (AEs) One Month After Radiofrequency Ablation (RFA)
adverse eventsSorafenibPlacebo
Number of Treatment-Related Grade 1-4 Adverse Events (AEs) One Month After Radiofrequency Ablation (RFA)84

Adverse events

Collected over Adverse events were collected on treatment days 1-10 and the day 40 follow-up visit.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Sorafenib0/9 (0%)1/9 (11.1%)9/9 (100%)
Placebo0/10 (0%)1/10 (10%)10/10 (100%)
Most frequent serious events
Most frequent serious events
EventSorafenibPlacebo
LeukocytesInvestigations1/90/10
LymphopeniaInvestigations1/90/10
AST, SGOTInvestigations1/90/10
BilirubinInvestigations1/90/10
Liver, hemorrhageHepatobiliary disorders0/91/10
Most frequent other events
Showing 10 of 103
Most frequent other events
EventSorafenibPlacebo
AST, SGOTInvestigations8/98/10
ALT, SGPTInvestigations7/95/10
PlateletsInvestigations7/94/10
BilirubinInvestigations5/94/10
INRInvestigations5/95/10
Alkaline phosphataseInvestigations3/95/10
AnorexiaMetabolism and nutrition disorders4/92/10
Diarrhea w/o prior colostomyGastrointestinal disorders4/93/10
FatigueGeneral disorders4/93/10
HemoglobinBlood and lymphatic system disorders4/93/10

Baseline characteristics

The analysis population is comprised of all enrolled participants.

Age, Continuous
Age, Continuous(years)SorafenibPlaceboTotal
Mean69 ± 1066 ± 1168 ± 10
Sex: Female, Male
Sex: Female, Male(Participants)SorafenibPlaceboTotal
Female224
Male8816
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)SorafenibPlaceboTotal
Hispanic or Latino101
Not Hispanic or Latino8715
Unknown or Not Reported134
Region of Enrollment
Region of Enrollment(participants)SorafenibPlaceboTotal
United States101020
Present Liver Cirrhosis
Present Liver Cirrhosis(Participants)SorafenibPlaceboTotal
Count of participants101020
Present Portal Vein Thrombosis
Present Portal Vein Thrombosis(Participants)SorafenibPlaceboTotal
Count of participants156
Tumor Size - Short Axis
Tumor Size - Short Axis(centimeters)SorafenibPlaceboTotal
Mean4.4 ± 1.34.4 ± 1.44.4 ± 1.3
Tumor Size - Long Axis
Tumor Size - Long Axis(centimeters)SorafenibPlaceboTotal
Mean4.9 ± 1.75.3 ± 1.35.1 ± 1.5
08

Study locations

2 sites
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02215, United States
09

References and documents

Publications

  • Hakime 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. doi: 10.1148/radiol.2442061005. PubMed 17641366 ↗
  • Bockorny B, Bullock AJ, Abrams TA, Faintuch S, Alsop DC, Goldberg SN, Ahmed M, Miksad RA. Priming of Sorafenib Prior to Radiofrequency Ablation Does Not Increase Treatment Effect in Hepatocellular Carcinoma. Dig Dis Sci. 2022 Jul;67(7):3455-3463. doi: 10.1007/s10620-021-07156-2. Epub 2021 Jul 23. PubMed 34297268 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 13, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00813293
Lead sponsor
Beth Israel Deaconess Medical Center
Collaborators
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Bayer, Onyx Therapeutics, Inc., National Cancer Institute (NCI)
Responsible party
Andrea Bullock (Principal Investigator, Beth Israel Deaconess Medical Center) — Principal investigator
First posted
Dec 23, 2008
Start date
Jun 2009
Primary completion
Nov 2013
Completion
Nov 2013
Results posted
Jun 22, 2020
Last update
Jun 13, 2023

Study contacts

Andrea Bullock, MD, MPH
principal investigator · Beth Israel Deaconess Medical Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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