Primary objectives:* To evaluate efficacy of adjuvant 166Ho-radioembolization (166Ho-RE) after systemic 177Lu-dotatate in a non-comparative phase II study Secondary objectives:* To establish the safety and toxicity profile of adjuvant 166Ho-RE after…
ID
Source
Brief title
Condition
- Other condition
- Hepatobiliary neoplasms malignant and unspecified
- Endocrine neoplasms malignant and unspecified
Synonym
Health condition
lever- en galwegneoplasmata malgine en niet-gespecificeerd
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* Tumour response at 3 months
Secondary outcome
* Safety and toxicity profile of 166Ho-RE as adjuvant treatment after
177Lu-dotatate
* Changes in tumour markers
* Quality of Life (QoL)
* Biodistribution / Dosimetry
Background summary
Patients with gastroenteropancreatic neuroendocrine tumours (NET) often die
from intrahepatic disease or are excluded from liver-directed treatment because
of extrahepatic disease. Adjuvant liver-directed treatment is warranted to
control both intra- and extrahepatic disease.
Study objective
Primary objectives:
* To evaluate efficacy of adjuvant 166Ho-radioembolization (166Ho-RE) after
systemic 177Lu-dotatate in a non-comparative phase II study
Secondary objectives:
* To establish the safety and toxicity profile of adjuvant 166Ho-RE after
systemic treatment with 177Lu-dotatate.
* To evaluate Quality of Life (QoL).
* To evaluate biodistribution / dosimetry.
Study design
Interventional, treatment, non-randomized, open label, non-comparative, phase
II study
Intervention
166Ho-RE will be performed via a catheter during angiography
Study burden and risks
The burden for the patient consits of:
1 screening visite, 1 or 2 hospital admission for 48 hours and up to 6
outpatient visits. 8 blood samples for safety, 5 HRQOL questionnaires, 8
Physical examinations, 2 angiographies, 2 holmium-SPECT/CT-scans and 5
whole-body CT-scans.
Risks
Apart from the angiographic procedures and device related toxicity (such as
abdominal pain, nausea, vomiting, diarrhoea, fatigue, fever, tumour lysis
syndrome, radiation hepatitis, veno occlusive disease, carcinoid crisis, leuko-
and thrombopenia, peptic ulceration, pancreatitis, radiation pneumonitis,
radiation induced cholecystitis, spurious aneurysm and hematoma, infection or
inflammation of the arterial puncture wound, iatrogenic arterial dissection,
contrast-induced renal insufficiency, thromboembolic events), standard
radiological and nuclear medicine procedures are also used that may have their
inherent side effects. For the frequent blood sampling and/or pre- and
posthydration, an indwelling cannula may be used and this may be accompanied by
mild bruising and also, in rare cases, by transient phlebitis. After initial
irritation, the presence of an indwelling cannula is usually painless and
hardly noticeable. The same applies to single vein punctures for blood
sampling. A urethral catheter, if used, may also cause infection. The total
amount of blood withdrawn during the study will be up to 70 ml (normal blood
donation: 500 ml).
Benefits
It is anticipated that treatment with radioactive microspheres will reduce
tumour size and will improve quality of life as known from literature from
90Yttrium and as was observed in the HEPAR I trial. It is anticipated that the
gamma emission of 166Holmium will improve the safety of the procedure. In
addition, the difference in specific activity of 166Ho-PLLA-MS compared to the
currently available 90Yttrium may theoretically improve tumour response and
accordingly, liver specific progression-free survival.
Participation in this study may possibly produce useful scientific data for the
future. The maximum number of visits (n=9) (depending on time to tumour
progression) is comparable to a standard chemotherapy protocol. However, the
scheduling is different.
There are upto 6 extra visits compared to treatment with 90Y-MS, which is a
routinely performed treatment in the UMC Utrecht.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
* Patients must have given written informed consent (Appendix IV and V).
* Female or male aged 18 years and over.
* Confirmed histological diagnosis NET, including bronchial carcinoids, and metastatic malignancy with liver metastases without standard therapeutic options for treatment including chemotherapy or surgery.
* Patients must have been treated with 4 cycles of 200 mCi 177Lu-dotatate, the last cycle within 20 weeks of 166Ho-RE.
* Life expectancy of 12 weeks or longer.
* World Health Organisation (WHO) Performance status 0-2 (see Appendix VI).
* Liver disease with three or more measurable liver lesions according to the RECIST 1.1 criteria.
* Negative pregnancy test for women of childbearing potential.
Exclusion criteria
* Brain metastases or spinal cord compression, unless irradiated at least 4 weeks prior to the date of the experimental treatment and stable without steroid treatment for at least 1 week.
* Radiation therapy within the last 4 weeks before the start of study therapy.
* The last dose of prior chemotherapy has been received less than 4 weeks prior the start of study therapy.
* Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy.
* Serum bilirubin > 1.5 x Upper Limit of Normal (ULN).
* Glomerular filtration rate <35 ml/min, determined according to the Modification of Diet in Renal Disease formula.
* Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) > 5 x ULN.
* Leukocytes < 2.0 10EXP9/l and/or platelet count < 50 10EXP9/l.
* Patients who are declared incompetent
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 | NCT02067988 |
| CCMO | NL45329.041.13 |