To assess the time to progression after TACE-DEB and after SBRT in a comparable population of patients diagnosed with HCC.
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study will be time to progression, defined as time
from randomization to radiological progression.
Secondary outcome
Secondary endpoints will be:
-Time to local recurrence
-Response rate (complete and partial response)
-Overall survival
-Toxicity
-Quality of life.
Background summary
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).
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
Study 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, and phase II study.
Intervention
Patients with HCC will be randomized to receive the standard treatment,
TACE-DEB loaded with doxorubicin or the experimental arm, SBRT.
Study burden and risks
Data regarding toxicity after TACE-DEB provide evidence of a relatively safe
treatment. Most complications are only minor with an increase in transaminase
levels and total bilirubin.
Previous experience with SBRT in HCC patients has been reported in several
papers with high rates of local tumor control and limited toxicity.
Expected risk of hepatic toxicity or radiation induced liver disease with the
SBRT protocol used in this trial is expected to be * 5%. Radiation-induced
liver disease will be defined as anicteric ascites and elevation of alkaline
phosphatase levels to at least two fold above the pretreatment values in
absence of tumor progression. The bleeding risk in patients with portal
hypertension is expected to be low. In fact only patients with a limited risk
of bleeding will be considered for this study.
Other organs at risk constraints comply with international accepted
recommendations. The expected associated toxicity as perforation for stomach,
esophagus and bowel is low. Risks associated to fiducial marker implant are
also limited. The most important is the risk of intrahepatic bleeding. In order
to minimize this risk of complications, the implant will be carried out by
trained interventional radiologists. The patient will remain hospitalized
during 4-5 hours after the implant.
No DSMB will be installed due to the minimal risk associated with the
participation in this study. No interim analysis is planned for this study.
Radiological endpoints will be centrally reviewed by an independent radiologist
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
-Patients diagnosed with HCC (follow the diagnostic algorithm recommended by the EASL*EORTC Clinical Practice Guidelines 2012). The treatment can be delivered prior to liver transplantation.
-Barcelona Clinic Liver Cancer Stage System class A-B
-One to three tumors with at most up to a cumulative diameter of * 6 cm measured in all 3 axes. In case of multiple lesions, the most favorable setting would be that all are eligible for TACE-DEB. If only one or two lesions are eligible for TACE-DEB, and the others are eligible for ablation, the patient can still be included in the study. Satellite nodules count as independent lesions.
-Earlier treatments with ablation are allowed until a maximum of 3 lesions, including the one, or ones, that will be randomized in the study. Lesions previously treated with ablation should not have exceeded a diameter of 3cm.
-Measurable disease on CT/MRI-scan, according to mRECIST criteria for HCC within 6 weeks prior to randomization
-Tumor visibility on CT
-None or cirrhosis Child-Pugh A
-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 preferable * 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).
-Uncontrolled portal hypertension (high bleeding risk). If gastroscopy has been performed, untreated esophageal varices grade III or IV.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL51318.078.14 |
| OMON | NL-OMON28819 |