NCT01507064

Neoadjuvant Sorafenib Therapy Prior to Laser Ablation for Hepatocellular Carcinoma

Randomized Controlled Phase II Trial Of Neoadjuvant Sorafenib Therapy Prior to Thermal Ablation for Hepatocellular Carcinoma More Than 4 cm in Size

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Cardarelli Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether neoadiuvant therapy with sorafenib increases the efficacy of thermal ablation in inducing the necrosis of hepatocellular carcinoma.

Detailed description

BACKGROUND AND AIM Image-guided laser ablation (LA), minimally invasive procedure, is a potentially viable treatment option for achieving focal thermal destruction of hepatocellular carcinoma (HCC) that cannot be treated with surgery. Both techniques are effective for the destruction of small (\<3 cm) tumors, but the success rate for index tumors larger than 4 cm in diameter is lower. A cause of the difficulty in treating larger tumors is represented by the heat-sink effect of tumor blood flow that limits the size of tumor ablation by drawing heat away from the tumor nodule. Surgical (Pringle maneuver) and endovascular (transarterial chemoembolization) techniques have been used to reduce the tumor blood flow during or before thermal ablation, but these techniques require invasive procedures that may decrease the patient acceptance and increase the risk of complications. Sorafenib is a multikinase inhibitor that has been approved for the treatment of advanced HCC. One of the main effect of this drug is to block vascular endothelial growth factor (VEGF) pathway, Flt-3, c-KIT, and fibroblast growth factor receptor 1, that have been shown to mediate tumor angiogenesis, reducing intratumoral blood flow. An experimental study in mice with renal cell carcinoma implanted subcutaneously, showed that treatment with sorafenib before ablation resulted in markedly decreased cancer microvessel density and significantly larger zones of radiofrequency-induced coagulation necrosis (1). The purpose of this study is to determine if sorafenib improves the effectiveness of laser ablation (LA) for the treatment of HCC larger than 4cm in size. 1\. Hakimé 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, 244, 464-470. STUDY DESIGN Participants will be randomized to receive either sorafenib (400mg twice a day) or placebo continuously for 4 weeks (on days 1-28). LA will be performed on day 29. On days 0 and 28, and 1, 6, and 12 months after LA, patients will undergo to a physical exam. Adverse events will be recorded using a pre-planned questionnaire in accordance with the "common toxicity criteria". Occurrence and characteristics of postablation syndrome will also be recorded. During a six-month period, if clinically indicated LA procedures preceded by a four-week sorafenib treatment, may be repeated up to three times. Laboratory values will be assessed on days 0 and 28, and 1, 6, and 12 months after the first LA procedure. Upper gastrointestinal endoscopy will be done before starting drug treatment. A tumor biopsy will be obtained at the time of the first LA. A CT or MRI scan will be performed at the time of inclusion in the study, at 1, 6, and 12 months after LA.

Conditions

• Hepatocellular Carcinoma

Interventions

Type	Name	Description
DRUG	Sorafenib	tablets 200mg dosage: 400mg bid duration: 4 weeks
PROCEDURE	laser ablation (LA)	For LA, we use a commercially available system (Echolaser XVG system, Esaote El.En., Florence, Italy) and four optical fibers,inserted into the tumor through four 21-gauge needles. The tips of the needles will be positioned at a distance of 15mm from each other. When, after LA treatments, CT or MRI findings show a residual nodule activity of 10% or less, percutaneous ethanol injection may be done. If the residual activity is of 50% or more transarterial chemoembolization may be used.

Timeline

• Start date: 2012-01-01
• Primary completion: 2015-09-01
• Completion: 2016-09-01
• First posted: 2012-01-10
• Last updated: 2017-03-07

Locations

1 site across 1 country: Italy