To investigate the safety and feasibility of a personalized Ho-166-PLLA-MS TARE approach by using MRI guidance in inoperable patients with HCC.
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the safety and feasibility of MRI guided administration of
Ho-166-PLLA-MS in patients.
Secondary outcome
Secondary endpoints include response at 3, 6 and 12 months, and overall
survival.
Background summary
Each year, worldwide over 600,000 people develop hepatocellular carcinoma
(HCC). In case surgical or systemic therapies are not feasible, (loco)regional
therapies such as transarterial radioembolization (TARE) may be used. TARE is a
technique where radioactive microspheres are injected in the hepatic artery,
which mostly supplies the tumours contrary to the healthy liver tissue, which
is mostly supplied by the portal vein. The microspheres lodge in the
microvasculature, selectively irradiating the tumour tissue. Patient outcome
after TARE has been variable due to lack of tumor targeting. The Dosipshere-1
and SARAH study show that personalised TARE leading to a high tumour dose leads
to better patient outcome. In order to be able to better visualise the
distribution of microspheres, TARE microspheres with gamma emission and
paramagnetic properties were developed. By administering holmium-microspheres
(Ho-166-PLLA-MS) inside an MRI-scanner, the clinician can verify the
distribution of microspheres in the liver while administering the microspheres,
and adjust microsphere administration during treatment, leading to a more
personalised approach to traditional TARE, and possibly better patient outcome.
Study objective
To investigate the safety and feasibility of a personalized Ho-166-PLLA-MS TARE
approach by using MRI guidance in inoperable patients with HCC.
Study design
This is a single centre, interventional treatment, non-randomized, open label,
dose escalation study with an investigational medical device in at least 9
patients (financing for 15 patients).
Patients will undergo interventional radiological placement of an MR opaque
catheter, after which the patient is moved to the MRI, where administration of
microspheres is performed under MRI guidance. Microsphere distribution will be
evaluated regularly, and administration will be stopped after the healthy liver
dose has been reached (40-60-80 Gy) or tumours are saturated with microspheres.
Intervention
Ho-166-PLLA-MS will be administered using a medical device via a catheter
during MR imaging.
Study burden and risks
It is anticipated that treatment with radioactive microspheres will reduce
tumour size and will improve quality of life as known from literature from
holmium-166 and yttrium-90 TARE. Patient treatment will be planned with a
maximal healthy liver dose different to conventional treatment (40-60-80 Gy),
which could lead to additional burden to the patient (liver toxicity) but is
expected to have a potential benefit to patients, since the administered dose
will be monitored over time during treatment, and both tumour and healthy liver
dose will be optimized.
The additional burden for patients participating in the study consists of
treatment taking place at the MRI-scanner instead of the angio suite, as a
result of which treatment will take approximately 60-90 minutes longer than
usual. For treatment within this study, a total of 9 visits (one is a telephone
call) is required, most of which are part of regular patient care. Multiple
diagnostic scans will be performed outside regular patient care.
geert grooteplein zuid 10
Nijmegen 6524 GA
NL
geert grooteplein zuid 10
Nijmegen 6524 GA
NL
Listed location countries
Age
Inclusion criteria
1. Diagnosis of hepatocellular carcinoma
2. At least one lesion of 10 mm or more in the longest diameter on
contrast-enhanced MRI/CT
3. Patient is eligible for TARE as determined by the tumour board (in Dutch:
MDO)
4. Patient has a life expectancy of 12 weeks or longer
5. Patient has a WHO performance score of 0-2
Exclusion criteria
1. Extrahepatic disease that cannot be targeted during the TARE session
(enlarged lymph nodes in the liver hilus are allowed)
2. Radiation therapy, chemotherapy or major surgery within 4 weeks before
treatment
3. Serum bilirubin > 2.0 x the upper limit of normal
4. ALAT, ASAT, alkaline phosphatase (AF) > 5x the upper limit of normal
5. Glomerular filtration rate (GFR-MDRD) <35 ml/min
6. Leukocytes <4.0 * 109/L or platelet count <60 * 109/L
7. Significant heart disease that in the opinion of the physician increases the
risk of ventricular arrhythmia.
8. Pregnancy or breast feeding
9. Disease with increased chance of liver toxicity, such as primary biliary
cirrhosis or xeroderma pigmentosum
10. Patients ineligible to undergo MR-imaging (claustrophobia, metal implants,
etc)
11. Portal vein thrombosis of the main branch (more distal branches are allowed)
12. Evidence of clinically relevant, untreated portal hypertension combined
with grade 3 oesophageal varices
13. Untreated, active hepatitis
14. Body weight > 150 kg (because of maximum table load)
15. Severe allergy for i.v. contrast (Iomeron, Dotarem and/or Primovist)
16. Lung shunt > 30 Gy, as calculated using scout dose 166Ho SPECT/CT.
17. Uncorrectable extrahepatic deposition of scout dose activity. Activity in
the falciform ligament, portal lymph nodes or gallbladder are accepted.
18. Unstable final catheter position due to hepatic artery anatomy, which might
lead to dislocation of the catheter during transfer to the MRI.
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 |
|---|---|
| CCMO | NL81813.091.22 |