NCT02470533

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Apr 2015

Longer than P75 for phase_2

Geographic Reach
3 countries

11 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 30, 2015

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

June 8, 2015

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 12, 2015

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2020

Completed
Last Updated

January 27, 2021

Status Verified

January 1, 2021

Enrollment Period

5 years

First QC Date

June 8, 2015

Last Update Submit

January 25, 2021

Conditions

Liver Neoplasms

Outcome Measures

Primary Outcomes (1)

  • Time to progression

    4 years

Secondary Outcomes (5)

  • Time to local recurrence

    4 years

  • Response rate

    4 years

  • Overall survival

    4 years

  • Toxicity

    4 years

  • Quality of life

    4 years

Study Arms (2)

Transarterial chemoembolization

ACTIVE COMPARATOR

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

Stereotactic body radiation therapy

EXPERIMENTAL

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

Interventions

Radiation therapyRADIATION

6 fractions of 8-9Gy

Stereotactic body radiation therapy
chemoembolizationDEVICE

Up to 4 sessions

Transarterial chemoembolization

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

UH Antwerp

Antwerp, Belgium

Location

UH Leuven

Leuven, Belgium

Location

UH Lille

Lille, France

Location

Erasmus MC

Rotterdam, South Holland, Netherlands

Location

AMC

Amsterdam, Netherlands

Location

VU MC

Amsterdam, Netherlands

Location

LUMC

Leiden, Netherlands

Location

Maastro

Maastricht, Netherlands

Location

UMC Maastricht

Maastricht, Netherlands

Location

UMC St Radboud

Nijmegen, Netherlands

Location

UMC Utrecht

Utrecht, Netherlands

Location

MeSH Terms

Conditions

Liver Neoplasms

Interventions

RadiotherapyChemoembolization, Therapeutic

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

TherapeuticsEmbolization, TherapeuticHemostatic TechniquesTherapeutic Occlusion

Study Officials

  • Alejandra Mendez Romero, MD PhD

    Erasmus Medical Center

    PRINCIPAL INVESTIGATOR

  • Adriaan Moelker, MD PhD

    Erasmus Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD PhD

Study Record Dates

First Submitted

June 8, 2015

First Posted

June 12, 2015

Study Start

April 30, 2015

Primary Completion

April 30, 2020

Study Completion

April 30, 2020

Last Updated

January 27, 2021

Record last verified: 2021-01

Locations

BE(2)NL(8)FR(1)