To investigate whether using the ARC during 166Ho-RE increases the post-treatment tumor to non-tumor (T/N) activity concentration ratio, compared to using a standard end-hole microcatheter.
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the T/N activity concentration ratio. The primary
endpoint will be compared between the ARC and standard micocatheter infusions.
Secondary outcome
Secondary endpoints include mean absorbed doses of radioactivity in tumorous
and healthy liver tissue, infusion efficiency, the predictive value of
166Ho-scout dose and tumor response. These enpoints will be compared between
the ARC and standard micocatheter infusions. A dose-response relationship,
clinical toxicity and overall survival will be assessed for the entire cohort.
Background summary
Radioembolization (RE) is a safe and effective locoregional therapy for
unresectable chemorefractory colorectal cancer liver metastases (CRCLM).
Holmium-166 micorspheres (166Ho) have proven to be a safe and effective
substitute for routinely used yttrium-90 microspheres (90Y), while their
superior imaging capacities allow for visualization of the intrahepatic
microsphere biodistribution and quantitative assessment of radioactive doses
absorbed by tumorous and healthy liver tissue on single-photon emission
computed tomography (SPECT-CT) and magnectic resonance imaging (MRI).
Furthermore, a scout dose of identical microspheres can be administered on the
same day to predict the intrahepatic distribution of the therapeutic
166Ho-microspheres. This is an important advantage over routine RE practice
with 90Y-microspheres, which rely on an inaccurate simulation with different
particles (technetium-99m-labelled macro-albumin aggregates (99mTc-MAA)) in the
week(s) before treatment. Recently, an infusion system has been developed that
may further complement the treatment-efficacy of 166Ho-RE. It has been
demonstrated that an anti-reflux infusion system significantly increases the
infusion efficiency of intra-arterial embolotherapy by near-complete
elimination of reflux, and induces a down-stream pressure gradient that may
enhance tumor penetration. These effects may increase tumor absorbed doses
after 166Ho-RE, which should translate in improved patient outcome.
Furthermore, the unique centroluminal catheter position during infusion may
further increase the accuracy of the 166Ho-scout dose as a predictor for the
intrahepatic distribution of therapeutic 166Ho-microspheres by limiting laminar
flow patterns, which are important contributors to a disproportionate
microsphere distribution after infusion through a standard end-hole
microcatheter.
Study objective
To investigate whether using the ARC during 166Ho-RE increases the
post-treatment tumor to non-tumor (T/N) activity concentration ratio, compared
to using a standard end-hole microcatheter.
Study design
Clinical phase 2, within-subject randomized controlled trial.
Intervention
Scout and therapeutic doses of 166Ho-microspheres will be administered in the
hepatic artery during two sequential procedures on the same day. In all
subjects, the use of the ARC and the standard end-hole catheter will be
randomly allocated to the infusion site (left and right hepatic artery).
Study burden and risks
166Ho-RE will largely be performed as in previous phase I-II clinical trials,
and the patient burden is comparable to routine yttrium-90 radioembolization.
The anti-reflux infusion system used in this study is a CE-marking and
FDA-approved medical device (for the intended purpose) that has already been
used extensively in clinical care. Furthermore, it has been shown that the use
of the ARC eliminates the need for coil embolization, and reduced treatment
complexity, procedure time, contrast- and radiation burden.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
* Written informed consent.
* Histopathologically confirmed diagnosis of adenocarcinoma of the colon or rectum.
* Hepatic metastases with measurable morphological appearance (* 1 cm) on cross sectional imaging, located in the right and left hepatic arterial perfusion territory.
* Unresectable, liver dominant disease.
* Progressive disease after second line chemotherapy or no further chemotherapeutical treatment options due to severe side effects or unwillingness of the patient to undergo systemic chemotherapy.
* Age * 18 years.
* Expected adequacy of follow-up.
Exclusion criteria
* WHO (World health organization) performance score > 2
* Inadequate bone marrow function (hemoglobin < 6.0 mmol/l, leukocyte count < 3.0 x 10^9/l, platelet count < 75x 10^9/l), inadequate liver function (bilirubin > 35 µmol/l, aspartate aminotransferase / alanine aminotransferase (AST/ALT) > 5 x upper limit of normal (ULN)) or inadequate renal function (creatinine > 1.5 x ULN).
* Prior hemihepatectomy.
* Compromised biliary system (biliary stent or hepaticojejunostomy).
* Child Pugh score B7 or worse.
* Active hepatitis B or C.
* Main portal vein thrombosis on CT (or previous portal vein embolization).
* Severe celiac axis stenosis on CT.
* Unsuitable hepatic arterial anatomy on CT.
* Treatment with systemic chemotherapy within 4 weeks prior to radioembolization.
* Previous participation in a study classified as class III by a radiation safety committee
* Bleeding diathesis.
* Pregnancy or breast feeding.
* Life expectancy < 3 months.
* Patients who are declared incompetent.
* Any condition that prevents from safe treatment with radioembolization.
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 | NCT02208804 |
| CCMO | NL48905.041.14 |