Neoadjuvant Sorafenib Therapy Prior to Laser Ablation for Hepatocellular Carcinoma (LANEX)

March 4, 2017 updated by: Giovan Giuseppe Di Costanzo, Cardarelli Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Napoli, Italy, 80131
        • UOSC Epatologia - Cardarelli Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 18-80 years
  • ECOG = 0 or 1
  • No liver decompensation (Child-Pugh <8), bilirubin <3mg/dL
  • Patients with unresectable HCC or who refused surgery
  • Confirmed HCC by pathology or by AASLD imaging guidelines
  • At least one HCC nodule (index tumor) accurately measured as 4-8cm in diameter on baseline imaging
  • No prior therapy for the index tumor
  • No prior systemic treatment for HCC within 4 weeks of study entry
  • LA clinically indicated for index tumor
  • Hemoglobin >9.0 g/dl; Platelet count correctable to >50,000/mm3; INR correctable to <2.0.

Exclusion Criteria:

  • Other severe concomitant diseases that may reduce life expectancy
  • Participants currently receiving any other study agents
  • Cancer vascular invasion or extrahepatic metastasis
  • Uncontrolled hypertension
  • Thrombotic events or myocardial infarction within the past 6 months
  • Hemorrhage/bleeding event within 4 weeks
  • Evidence of severe or uncorrectable bleeding diathesis or coagulopathy
  • Contraindication to or inability to undergo the LA procedure
  • Human immunodeficiency virus (HIV) infection
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Group A
Patients who undergo to LA without sorafenib pretreatment
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.
EXPERIMENTAL: Group B
Patients who are treated with sorafenib before LA
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.

Drug: Sorafenib
tablets 200mg dosage: 400mg bid duration: 4 weeks
Other Names:
  • Nexavar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effectiveness of sorafenib in increasing the effectiveness of laser ablation (LA)
Time Frame: 1 year
Measures: complete tumor ablation rate (according to the mRECIST), time-to-recurrence (in complete response subgroup), time-to-progression (in partial response subgroup).
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of sorafenib treatment prior to LA.
Time Frame: 6 months
Measure: incidence and grade of adverse events in patients treated with sorafenib (group B)
6 months
Survival in the two treatment groups
Time Frame: 2 years
Measured from the date of LA until the date of death or last visit
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cardarelli Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2012

Primary Completion (ACTUAL)

September 1, 2015

Study Completion (ACTUAL)

September 1, 2016

Study Registration Dates

First Submitted

January 5, 2012

First Submitted That Met QC Criteria

January 6, 2012

First Posted (ESTIMATE)

January 10, 2012

Study Record Updates

Last Update Posted (ACTUAL)

March 7, 2017

Last Update Submitted That Met QC Criteria

March 4, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • epatologia2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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