Back to results

Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer

Primary Purpose

Hepatocellular Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Sorafenib

radiofrequency ablation

About this trial

This is an interventional treatment trial for Hepatocellular Cancer focused on measuring Hepatocellular Cancer, HCC, Liver Cancer, radiofrequency ablation, RFA, sorafenib, nexavaar, liver directed therapy, interventional radiology

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Sorafenib

Placebo

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

Coagulation Zone Diameter-Short Axis

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

Coagulation Zone Diameter-Long Axis

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

Coagulation Zone Volume

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

Secondary Outcome Measures

Feasibility Rate

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

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.

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.

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.

Full Information

NCT ID

NCT00813293

First Posted

December 22, 2008

Last Updated

June 9, 2023

Sponsor

Beth Israel Deaconess Medical Center

Collaborators

Dana-Farber Cancer Institute, Brigham and Women's Hospital, Bayer, Onyx Therapeutics, Inc., National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00813293

Brief Title

Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

June 2009 (Actual)

Primary Completion Date

November 2013 (Actual)

Study Completion Date

November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Beth Israel Deaconess Medical Center

Collaborators

Dana-Farber Cancer Institute, Brigham and Women's Hospital, Bayer, Onyx Therapeutics, Inc., National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Cancer

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sorafenib

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Sorafenib

Other Intervention Name(s)

Nexavar

Intervention Type

Procedure

Intervention Name(s)

radiofrequency ablation

Other Intervention Name(s)

RFA

Primary Outcome Measure Information:

Title

Coagulation Zone Diameter-Short Axis

Description

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)

Title

Coagulation Zone Diameter-Long Axis

Description

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)

Title

Coagulation Zone Volume

Description

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 Outcome Measure Information:

Title

Feasibility Rate

Description

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

Title

Number of Treatment-Related Grade 1-4 Adverse Events (AEs) by Day 9

Description

Time Frame

Day 9

Title

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

Description

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)

Title

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

Description

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andrea Bullock, MD, MPH

Organizational Affiliation

Beth Israel Deaconess Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Dana-Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Beth Israel Deaconess Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

17641366

Citation

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.

Results Reference

background

PubMed Identifier

34297268

Citation

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.

Results Reference

derived

Learn more about this trial

Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer

We'll reach out to this number within 24 hrs