Sorafenib Therapy Prior to Radiofrequency Ablation for Intermediate Sized Hepatocellular Cancer

NCT00813293 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 08-256K23CA139005IST000508
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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.

Conditions

Hepatocellular Cancer

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Coagulation Zone Diameter-Short Axis

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

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

• Coagulation Zone Diameter-Long Axis

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

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

• Coagulation Zone Volume

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

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

Secondary Outcomes (4)

• Feasibility Rate

  Up to day 14 since enrollment

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

  Day 9

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

  Up to day 14 (target day 10 RFA)

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

  Up to day 40 post RFA (target 30 days)

Study Arms (2)

Sorafenib

EXPERIMENTAL

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

PLACEBO COMPARATOR

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

Sorafenib DRUG

Also known as: Nexavar

Sorafenib

radiofrequency ablation PROCEDURE

Also known as: RFA

Placebo; Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Dana-Farber Cancer Institute: collaborator
• Brigham and Women's Hospital: collaborator
• Bayer: collaborator
• Onyx Therapeutics, Inc.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (2)

• 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.

  PMID: 17641366 BACKGROUND

• 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.

  PMID: 34297268 DERIVED

MeSH Terms

Conditions

Liver Neoplasms

Interventions

Sorafenib; Radiofrequency Ablation

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Radiofrequency Therapy; Therapeutics; Ablation Techniques; Surgical Procedures, Operative

Limitations and Caveats

This study is limited by small sample size.

Results Point of Contact

• Title: Andrea Bullock MD, MPH
• Organization: Beth Israel Deasoness Medical Center

abullock@bidmc.harvard.edu

Study Officials

• Andrea Bullock, MD, MPH

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 22, 2008
• First Posted: December 23, 2008
• Study Start: June 1, 2009
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: June 13, 2023
• Results First Posted: June 22, 2020

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)