Clinical trial NCT00813293: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatocellular Cancer
Keywords: Hepatocellular Cancer
HCC
Liver Cancer
radiofrequency ablation
RFA
sorafenib
nexavaar
liver directed therapy
interventional radiology
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
name: Brigham and Women's Hospital
name: Bayer
name: Onyx Therapeutics, Inc.
name: National Cancer Institute (NCI)
First posted: 2008-12-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Coagulation Zone Diameter-Short Axis
timeFrame: Up to day 50 from study enrollment (target 30 days after RFA)
measure: Coagulation Zone Diameter-Long Axis
timeFrame: Up to day 50 from study enrollment (target 30 days after RFA)
measure: Coagulation Zone Volume
timeFrame: Up to day 50 from study enrollment (target 30 days after RFA)
Secondary outcomes:
measure: Feasibility Rate
timeFrame: Up to day 14 since enrollment
measure: Number of Treatment-Related Grade 1-4 Adverse Events (AEs) by Day 9
timeFrame: Day 9
measure: Number of Treatment-Related Grade 1-4 Adverse Events (AEs) on Day of Radiofrequency Ablation (RFA)
timeFrame: Up to day 14 (target day 10 RFA)
measure: Number of Treatment-Related Grade 1-4 Adverse Events (AEs) One Month After Radiofrequency Ablation (RFA)
timeFrame: Up to day 40 post RFA (target 30 days)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Andrea Bullock, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.