Primary objective:To establish the safety and toxicity profile of individualized 166Ho-RE in patients with hepatocellular carcinoma. Secondary objectives:• To evaluate efficacy of individualized 166Ho-RE.• To evaluate biodistribution / dosimetry.•…
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety, expressed as the rate of unacceptable toxicity.
Secondary outcome
• Tumor response.
• Biodistribution / Dosimetry.
• Changes in tumor marker alpha-fetoprotein (AFP).
• Quality of Life (QoL).
• Changes in hepatic function as determined by hepatobiliary scintigraphy.
• Changes in Child Pugh score.
• To compare study results with HEPAR Primary study results.
Background summary
Patients with hepatocellular carcinoma often die from intrahepatic disease
because current treatment options are limited. Local treatment using
166Ho-radioembolization (166Ho-RE) offers a safe and effective treatment.
Because 166Ho-microspheres are used as a scout dose for treatment simulaton and
for the actual treatment itself, a tailored approach can be used. This concept
has proven to be more predictive than the 90Y-radioembolization concept
(current standard-of-care), which is a based on a surrogate scout dose (i.e.
99mTc-MAA). A personal treatment plan may be used for 166Ho-radioembolization
to optimize efficacy, based on scout dose distribution. However, individualized
treatment planning inherently leads to treatment doses that deviate from the
currently approved 'one-size-fits-all' approach (i.e. 60 Gy average absorbed
dose for all patients). Therefore, safety of individualized 166Ho-RE will be
evaluated first to validate safety and confirm safety thresholds. These
thresholds will be used in subsequent randomized controlled studies.
Study objective
Primary objective:
To establish the safety and toxicity profile of individualized 166Ho-RE in
patients with hepatocellular carcinoma.
Secondary objectives:
• To evaluate efficacy of individualized 166Ho-RE.
• To evaluate biodistribution / dosimetry.
• To evaluate tumor marker response.
• To evaluate quality of life.
• To evaluate hepatic function.
• To evaluate (de)compensation of the liver.
• To compare study results with HEPAR Primary study results (i.e.
non-individualized 166Ho-RE).
Study design
Multi-center, interventional, treatment, non-randomized, open label,
non-comparative, early clinical safety study. The study is a collaboration
between UMC Utrecht and Erasmus MC Rotterdam. Recruitment and treatment of
patients will take place in both centers.
Intervention
Individualized 166Ho-RE will be performed via a catheter during angiography.
Dosimetry-based treatment planning will be individualized based on Q-Suite*
software.
Study burden and risks
It is anticipated that treatment with radioactive microspheres will reduce
tumor size and will improve quality of life. It is anticipated that the γ-
emission of the radioactive 166Ho will improve the safety of the procedure by
enabling pre-treatment distribution analysis after scout dose imaging and
subsequent dosimetry-based individualized treatment planning. Also the
differences in specific activity of 166Ho-microspheres and the dose rate
compared to the currently available 90Y-microspheres may theoretically improve
tumor response and accordingly, liver specific progression-free survival.
Regular medical check-ups during the study can be seen as an additional
benefit.
Apart from the angiographic procedures and device-related toxicity, standard
radiological and nuclear procedures are also used, which may have inherent side
effects. For the frequent blood sampling and/or pre- and post-hydration, an
indwelling cannula may be used and this may be accompanied by mild bruising and
also, in rare cases, by transient inflammation of the vessel wall (phlebitis).
The same applies to single vein punctures for blood sampling. When needed, the
use of a urethral catheter may also cause infection. The total amount of blood
withdrawn during the study will be up to 100 ml (normal blood donation: 500
ml).
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
1. Patients must have given written informed consent.
2. Female or male aged 18 years and over.
3. 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.2, 4 LR-5 and LR- 4
based on Liver Imaging Reporting and Data System can be included.
4. No curative treatment options (resection, transplant, or in case of solitary
tumor <5 cm, RFA).
5. Life expectancy of at least 6 months.
6. ECOG Performance status 0-1.
7. Liver-dominant disease (maximum 5 lung nodules all <=1.0 cm, solitary
clinically stable adrenal metastasis, and mesenteric or portal lymph nodes all
<=2.0 cm are accepted).
8. Child-Pugh class A5-6 or B7 (only for patients with known cirrhosis).
9. At least one measurable liver lesion according to the modified RECIST
criteria.
10. Negative pregnancy test for women of childbearing potential. Female
patients of childbearing potential should use a 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 1 year postmenopausal or surgically
sterile during their participation in this study (from the time they sign the
consent form), to prevent pregnancy
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
1. Evidence of significant extrahepatic disease (MRI-scan liver and multiphase
abdominal CT as well as a thoracic CT are routinely performed at screening).
2. Hepatic radiation therapy within the last 4 weeks before the start of study
therapy.
3. Previous or current treatment with RE. Previous treatment with TACE,
surgery, RFA, and previous or current treatment with sorafenib are allowed.
4. Major surgery within 4 weeks or incompletely healed surgical incision before
starting study therapy.
5. Serum bilirubin >34.2 micromole/L (2 mg/dL).
6. Glomerular filtration rate <35 ml/min.
7. Non-correctable INR >1.5 in case of femoral approach (as opposed to radial).
8. Leukocytes <2 109/l and/or platelet count <50 109/l.
9. Significant cardiac event (e.g. myocardial infarction, superior vena cava
(SVC) 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.
10. Pregnancy or breastfeeding.
11. Patients suffering from psychic disorders that make a comprehensive
judgment impossible, such as psychosis, hallucinations and/or depression.
12. Patients who are declared incapacitated.
13. Previous enrollment in the present study.
14. Male patients who are not surgically sterile or 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 a partner.
15. Evidence of untreated, clinically significant grade 3 portal hypertension
(i.e. large varices at oesophago-gastro-duodenoscopy). In these cases, therapy
with non-selective beta-blocker (propranolol) or rubber band ligation should be
instituted according to accepted guidelines. In case of small varices,
prophylactic propranolol is advised.
16. Portal vein thrombosis (tumor and/or bland) of the main branch (diagnosed
on contrast enhanced transaxial images). Involvement of the right or left
portal vein branches and more distal is accepted.
17. Untreated active hepatitis. In case of detectable viral HBV load,
appropriate treatment should be instituted.
18. Transjugular intrahepatic portosystemic shunt (TIPS).
19. Body weight over 150 kg (because of maximum table load).
20. Severe allergy for intravenous contrast used (Visipaque®)(because of CT
evaluation, pre-treatment angiography and treatment angiography).
21. Lung shunt >30 Gy, as calculated using scout dose SPECT/CT.
22. Uncorrectable extrahepatic deposition of scout dose activity. Activity in
the falciform ligament, portal lymph nodes and gallbladder is accepted.
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
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03379844 |
| CCMO | NL74751.041.21 |