The RALLY study: dose finding study for radiation lobectomy using holmium-166 microspheres to improve resectability in patients with HCC.

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 24

Inclusion Criteria

In order to be eligible to participate in this study (including the biobank), a
subject must meet all of the following criteria: 1) Patients must have given
written informed consent. 2) Age >= 18 years. 3) ECOG Performance status 0-1
(Table 1). 4) Diagnosis of HCC, established according to the Netherlands HCC
guideline criteria (in line with American AASLD criteria): nodule >1 cm in a
patient at risk for HCC, with combination of arterial hypervascularity and
venous or delayed phase wash-out on multiphase CT-scan or MRI-scan. 5) HCC with
indication for major hepatectomy (i.e. >2 segments), as decided by
multidisciplinary tumour board. 6) HBS > 1.5%/min/m2 and < 2.7 %/min/m2. 7)
Negative pregnancy test for women of childbearing potential. Female patients of
child- bearing potential should use an highly effective acceptable method of
contraception (oral contraceptives, barrier methods, approved contraceptive
implant, long-term injectable contraception, intrauterine device or tubal
ligation) or should be more than one year postmenopausal or surgically sterile
during their participation in this study (from the time they sign the consent
form), to prevent pregnancy. 8) Patients with compensated Child-Pugh A and
unilobar BCLC-B or less (without evidence of portal hypertension).

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded
from participation in this study (including the biobank): 1) Evidence of
extrahepatic disease (MRI-scan liver and multiphase abdominal CT as well as a
thoracic CT are routinely performed at screening). 2) Any previous hepatic
external beam radiation therapy before the start of study therapy. 3) Previous
treatment with RE/RL. 4) Major surgery within 4 weeks or incompletely healed
surgical incision before starting study therapy. 5) Glomerular filtration rate
<35 ml/min, determined according to the Modification of Diet in Renal Disease
formula. 6) Non correctable INR > 1.5. 7) Significant cardiac event (e.g.
myocardial infarction, superior vena cava syndrome, New York Heart Association
(NYHA) classification of heart disease >= 2 within 3 months before entry, or
presence of cardiac disease that in the opinion of the investigator increases
the risk of ventricular arrhythmia. 8) Pregnancy or breastfeeding. 9) Patients
suffering from psychic disorders that make a comprehensive judgment impossible,
such as psychosis, hallucinations and/or depression. 10) Patients who are
declared incompetent. 11) Previous enrolment in the present study. 12) Patients
who do not use an acceptable method of contraception during their participation
in this study (from the time they sign the consent form) to prevent pregnancy.
In case of female: are less than 1 year postmenopausal and not using an
acceptable method of contraception. Patients who had surgical sterilization may
be included. 13) Any contraindication precluding surgery, with the exception of
insufficient FLR as defined by HBS. 14) Portal vein thrombosis (tumour and/or
bland) (diagnosed on contrast enhanced transaxial images). 15) Untreated active
hepatitis. In case of detectable viral HBV hepatitis B virus load, treatment
with a nucleos(t)ide analog such as entecavir or tenofovir should be
instituted. 16) Transjugular intrahepatic portosystemic shunt. 17) Body weight
over 150 kg (because of maximum table load). 18) Severe allergy for intravenous
contrast (Visipaque®). 19) Lung shunt > 30 Gy, as calculated using
166Ho-microspheres scout dose using SPECT/CT. 20) Not correctable extrahepatic
deposition of scout dose activity. Activity in the falciform ligament, portal
lymph nodes and gallbladder is accepted. 21) Any systemic therapy (including
transcatheter arterial chemoembolization) prior to the start of study therapy.
RFA or previous resection (> 4 weeks) is accepted. 22) Leukocytes <2 109/L
and/or platelet count <50 109/L. Serum bilirubin >34.2 micromol/L (2 mg/dL).

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The maximum tolerated radiation dose will be determined using the CTCAE v5.0<br /><br>methodology. Toxicities exceeding grade 3 that were deemed definitely, probably<br /><br>or possibly related to the administration of 166Ho-microspheres will be defined<br /><br>as a dose-limiting toxicity (DLT). Exceptions will be made for the expected<br /><br>lymphopenia, elevated liver enzymes and post-embolization syndrome. FLR<br /><br>response will be assessed using HBS. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Tumour response will be evaluated using the mRECIST criteria. QoL will be<br /><br>assessed using the questionnaire EORTC QLQ C30 and HCC18 as well as the BPI<br /><br>questionnaire.</p><br>