Hepatocellular CarcinomaPhase 2LANEXNCT01507064
Neoadjuvant Sorafenib Therapy Prior to Laser Ablation for Hepatocellular Carcinoma
A Phase 2 study testing Sorafenib and laser ablation (LA) in people with Hepatocellular Carcinoma, run by Cardarelli Hospital at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Sorafenib and laser ablation (LA)
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2012to Sep 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- 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
- Being tested
- Sorafenib, laser ablation (LA)
- Keywords
- hepatocellular carcinoma, sorafenib, laser ablation
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Also called Nexavar
tablets 200mg dosage: 400mg bid duration: 4 weeks
laser ablation (LA)Procedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | Patients who undergo to LA without sorafenib pretreatment Receives: Procedure: laser ablation (LA) |
| Group B | Experimental | Patients who are treated with sorafenib before LA Receives: Drug: Sorafenib; Procedure: laser ablation (LA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effectiveness of sorafenib in increasing the effectiveness of laser ablation (LA)
Measures: complete tumor ablation rate (according to the mRECIST), time-to-recurrence (in complete response subgroup), time-to-progression (in partial response subgroup).
Measured: 1 year
Secondary outcomes (2)
Safety of sorafenib treatment prior to LA.
Measure: incidence and grade of adverse events in patients treated with sorafenib (group B)
Measured: 6 months
Survival in the two treatment groups
Measured from the date of LA until the date of death or last visit
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2012 (estimated)
- Study startJan 2012
- Primary completionSep 2015
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cardarelli Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovan Giuseppe Di Costanzo, Cardarelli Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01507064
- Sponsor's protocol ID
- epatologia2
- Acronym
- LANEX
- Status last verified
- Mar 2017
- First submitted
- 5 Jan 2012
- Last updated
- 7 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Phase II Trial Of Neoadjuvant Sorafenib Therapy Prior to Thermal Ablation for Hepatocellular Carcinoma More Than 4 cm in Size
- ClinicalTrials.gov ID
- NCT01507064
- Acronym / sponsor ID
- LANEX / epatologia2
- Conditions
- Hepatocellular Carcinoma
- Keywords
- hepatocellular carcinoma, sorafenib, laser ablation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Cardarelli HospitalUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 10 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Procedure: laser ablation (LA)Patients who undergo to LA without sorafenib pretreatment |
| Group B | Experimental | Drug: Sorafenib, Procedure: laser ablation (LA)Patients who are treated with sorafenib before LA |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SorafenibAlso: Nexavartablets 200mg dosage: 400mg bid duration: 4 weeks | Drug | Group B |
| 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. | Procedure or surgery | Group A, Group B |
Primary outcome
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).
2 secondary outcomes
Safety of sorafenib treatment prior to LA.
Time frame: 6 months
Survival in the two treatment groups
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib and laser ablation (LA) in people with Hepatocellular Carcinoma, run by Cardarelli Hospital at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effectiveness of sorafenib in increasing the effectiveness of laser ablation (LA) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2017.