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Transarterial Chemoembolization Versus Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma (TRENDY)

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ClinicalTrials.gov Identifier: NCT02470533
Recruitment Status : Recruiting
First Posted : June 12, 2015
Last Update Posted : June 6, 2017
Sponsor:
Collaborators:
Dutch Cancer Society
UMC Utrecht
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
VU University of Amsterdam
Radboud University
Maastricht University Medical Center
Maastro Clinic, The Netherlands
Leiden University Medical Center
Universitaire Ziekenhuizen Leuven
University Hospital, Antwerp
University Hospital, Lille
Information provided by (Responsible Party):
Alejandra Mendez Romero, Erasmus Medical Center

Brief Summary:

Rationale:

This study will compare head to head in patients with hepatocellular carcinoma (HCC) ineligible for surgery or radiofrequency ablation, the standard treatment arm, transarterial chemoembolization with drug-eluting beads (TACE-DEB), with the experimental arm, stereotactic body radiation therapy (SBRT). The investigators hypothesis is that the time to progression is more favorable after SBRT than after TACE-DEB. The expected time to include the required patients for this trial will be four years.

To the best of the investigators knowledge this study will be the first in the world that will compare both techniques in a randomized trial.

Objective:

To assess the time to progression after TACE-DEB and after SBRT in a comparable population of patients diagnosed with HCC.

Study design:

Randomized, prospective, open-label, and phase II study.

Study population:

Patients diagnosed with HCC, Child-Pugh grade A, one to three tumors, cumulative diameter ≤ 6cm, and ≥ 18 years old.

Intervention:

Patients with HCC will be randomized to receive the standard treatment, TACE-DEB loaded with doxorubicin or the experimental arm, SBRT.

Main study parameters/endpoints:

The primary endpoint of this study will be time to progression, defined as time from randomization to radiological progression.

Secondary endpoints will be:

  • Time to local recurrence
  • Response rate (complete and partial response)
  • Overall survival
  • Toxicity
  • Quality of life.

Condition or disease Intervention/treatment Phase
Liver Neoplasms Radiation: Radiation therapy Device: chemoembolization Phase 2

Detailed Description:

Primary liver cancer, particularly hepatocellular carcinoma (HCC) is a major health problem. Curative therapies for HCC are considered hepatic resection, liver transplantation and radiofrequency ablation (RFA). Hepatic resection is preferred for patients with limited disease, non-cirrhotic livers or selected patients with Child-Pugh A cirrhosis. Unlike resection, liver transplantation treats the tumor and the underlying cirrhosis present in the liver. Candidates for liver transplantation are preferably those with cirrhosis and tumors that comply with the Milan criteria (single tumor <5cm or 1-3 tumors each of ≤ 3cm). Because most patients are not amenable to resection or liver transplantation, RFA has emerged as an effective treatment option. RFA is limited by the location of the tumor in the liver and by the tumor size with best results after RFA achieved for tumors ≤3cm. For patients that are not eligible for RFA due to large or multifocal tumors, transarterial chemoembolization with drug-eluting beads (TACE-DEB) is the preferred treatment.

Stereotactic body radiation therapy (SBRT) delivers a highly effective dose of irradiation to the tumor while maximally avoiding dose delivery to surrounding healthy structures. SBRT is offered as an ablative local treatment with reported high percentages of complete and partial responses with limited toxicity.

An international expert committee on HCC has recommended time to progression (TTP) as primary endpoint for phase II randomized trials. Although data is scarce the best published median TTP after TACE-DEB was 16 months and after SBRT 36.5months in a more or less comparable patient population (Barcelona Clinic Liver Cancer stage system A-C).

The present study will include patients not eligible for resection or RFA. Patients may be eligible for bridging or for down staging to transplantation. Well compensated liver cirrhosis (Child-Pugh A) and disease confined to the liver (one to three tumors cumulative diameter ≤ 6cm) is required. To our knowledge this trial will be the first in the world to compare TACE-DEB and SBRT. This trial may have a big impact on the control of the disease and may contribute to change the standard of care from a palliative to a more radical/curative intention in this patient population


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Transarterial Chemoembolization With Drug-Eluting Beads (Standard Arm) Versus Stereotactic Body Radiation Therapy (Experimental Arm) for Hepatocellular Carcinoma: A Multicenter Randomized Phase II Trial
Study Start Date : April 2015
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : April 2020

Arm Intervention/treatment
Active Comparator: Transarterial chemoembolization
Chemoembolization will be performed through a transarterial route delivering drug eluting beads, i.e. hydrogel-based microspheres (Biocompatibles UK, Ltd, HepaSphere Biosphere Medical) loaded with the chemotherapeutic agent doxorubicin.
Device: chemoembolization
Up to 4 sessions

Experimental: Stereotactic body radiation therapy
Risk-adapted dose prescription for delivering the highest possible tumor dose not exceeding the maximum dose in 6 fractions of 8-9 Gy, while hepatic normal tissue complication probability (NTCP) < of 5%
Radiation: Radiation therapy
6 fractions of 8-9Gy




Primary Outcome Measures :
  1. Time to progression [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Time to local recurrence [ Time Frame: 4 years ]
  2. Response rate [ Time Frame: 4 years ]
  3. Overall survival [ Time Frame: 4 years ]
  4. Toxicity [ Time Frame: 4 years ]
    Common toxicity criteria v4.0

  5. Quality of life [ Time Frame: 4 years ]
    EORTC Quality of life forms C-30 and HCC-18, Quality of life form Euro QoL5D



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients diagnosed with HCC Patients can be included if they require treatment prior to liver transplantation.
  • Barcelona Clinic Liver Cancer Stage System class A-B
  • One to three tumors of maximum cumulative diameter ≤ 6 cm measured in all 3 axes.
  • Measurable disease to be selected as a target on CT/MRI-scan, according to mRECIST criteria for HCC within 6 weeks prior to randomization (≥ 1cm at least in one dimension, suitable for repeated measurement, and arterial enhancement) [44].
  • Tumor visibility on CT
  • Child-Pugh A cirrhosis
  • Age ≥ 18 years
  • ECOG performance status 0-1
  • Albumin> 28 g/l, bilirubin < 50 µmol/l, INR < 2.3, AST/ALT < 5 times ULN, within 6 weeks prior to randomization
  • Platelets will be preferably ≥ 50x10E9/ l (if not, thrombocytes transfusion is allowed to ensure a safe procedure at the discretion of the interventional radiologist and gastroenterologist). Leukocytes > 1.5x10E9/l, Hb > 6 mmol/l, within 6 weeks prior to randomization
  • Written informed consent
  • Willing and able to comply to the follow-up schedule
  • Planned to start treatment within 6 weeks from randomization.

Exclusion Criteria:

  • Eligibility for resection or RFA
  • More than three tumors in the liver
  • Ascites
  • Any signs of acute viral or non-viral hepatitis
  • Encephalopathy
  • Vascular tumor invasion (contact with the vessel will not be considered contraindication).
  • Previous radiotherapy to the liver
  • Known current pregnancy
  • Distance from the tumor to the esophagus, stomach, duodenum, small bowel or large bowel < 0.5 cm on CT or on MRI (randomization imaging). Depending on the SBRT technique used, the minimum acceptable distance may vary and be larger for one technique compared to the other
  • Uncontrolled portal hypertension (high bleeding risk). If gastroscopy has been performed, untreated esophageal varices grade III or IV.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02470533


Contacts
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Contact: Alejandra Mendez Romero, MD PhD +31107040141 a.mendezromero@erasmusmc.nl
Contact: Adriaan Moelker, MD PhD +31107032886 a.moelker@erasmusmc.nl

Locations
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Belgium
UH Antwerp Recruiting
Antwerp, Belgium
Contact: Thomas Vanwolleghem, MD PhD         
Contact: Reinhilde Weytjens, MD PhD         
Principal Investigator: Thomas Vanwolleghem, MD PhD         
Sub-Investigator: Reinhilde Weytjens, MD PhD         
Sub-Investigator: Olivier d'Archambeau, MD PhD         
UH Leuven Recruiting
Leuven, Belgium
Contact: Chris Verslype, Prof         
Contact: Karin Haustermans, Prof         
Principal Investigator: Chris Verslype, Prof         
Sub-Investigator: Karin Haustermans, Prof         
France
UH Lille Recruiting
Lille, France
Contact: Stephane Cattan, MD PhD         
Contact: Xavier Mirabell, MD PhD         
Principal Investigator: Stephane Cattan, MD PhD         
Sub-Investigator: Xavier Mirabell, MD PhD         
Netherlands
Erasmus MC Recruiting
Rotterdam, ZH, Netherlands
Contact: Alejandra Mendez Romero, MD PhD         
Contact: Adriaan Moelker, MD PhD         
Principal Investigator: Alejandra Mendez Romero         
Sub-Investigator: Adriaan Moelker         
AMC Recruiting
Amsterdam, Netherlands
Contact: Henrike Westerveld, MD PhD         
Contact: Otto van Delden, Prof         
Principal Investigator: Henrike Westerveld, MD PhD         
Sub-Investigator: Otto van Delden, Prof         
VU MC Recruiting
Amsterdam, Netherlands
Contact: Niels Haasbeek, MD PhD         
Contact: Martijn Meijerink, MD PhD         
Principal Investigator: Niels Haasbeek, MD PhD         
Sub-Investigator: Martijn Meijerink, MD PhD         
LUMC Recruiting
Leiden, Netherlands
Contact: Mark Burgmans, MD PhD         
Contact: Mieneke Coenraad, MD PhD         
Principal Investigator: Mark Burgmans, MD PhD         
Sub-Investigator: Mieneke Coenraad, MD PhD         
Sub-Investigator: Karen Neelis, MD PhD         
Maastro Recruiting
Maastricht, Netherlands
Contact: Jeroen Buijsen, MD PhD         
Principal Investigator: Jeroen Buijsen, MD PhD         
UMC Maastricht Recruiting
Maastricht, Netherlands
Contact: Judith de Vos-Geelen, MD PhD         
Contact: Peter Jansen, Prof         
Principal Investigator: Judith de Vos-Geelen, MD PhD         
Sub-Investigator: Peter Jansen, Prof         
UMC St Radboud Recruiting
Nijmegen, Netherlands
Contact: Eric Tjwa, MD PhD         
Contact: Sjoerd Jenniskens, MD PhD         
Principal Investigator: Eric Tjwa, MD PhD         
Sub-Investigator: Sjoerd Jenniskens, MD PhD         
Sub-Investigator: Petra Braam, MD PhD         
UMC Utrecht Recruiting
Utrecht, Netherlands
Contact: Marco van Vulpen, MD PhD         
Contact: Karel van Erpecum, MD PhD         
Principal Investigator: Marco van Vulpen, MD PhD         
Principal Investigator: Karel van Erpecum, MD PhD         
Sponsors and Collaborators
Erasmus Medical Center
Dutch Cancer Society
UMC Utrecht
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
VU University of Amsterdam
Radboud University
Maastricht University Medical Center
Maastro Clinic, The Netherlands
Leiden University Medical Center
Universitaire Ziekenhuizen Leuven
University Hospital, Antwerp
University Hospital, Lille
Investigators
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Principal Investigator: Alejandra Mendez Romero, MD PhD Erasmus Medical Center
Principal Investigator: Adriaan Moelker, MD PhD Erasmus Medical Center

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Responsible Party: Alejandra Mendez Romero, MD PhD, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT02470533     History of Changes
Other Study ID Numbers: NL51318.078.14
First Posted: June 12, 2015    Key Record Dates
Last Update Posted: June 6, 2017
Last Verified: June 2017
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Liver Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases