Surefire Infusion System vs. Standard Microcatheter Use During Holmium-166 Radioembolization

Phase 2

• Conditions: Digestive System Neoplasms; Liver Diseases; Colorectal Neoplasms; Neoplasm Metastasis
• Interventions: Device: Holmium-166-poly (L-lactic acid) microspheres

• Registration Number: NCT02208804
• Lead Sponsor: UMC Utrecht

Brief Summary

The objective of the SIM trial is to investigate whether using the Surefire Infusion System during holmium-166 radioembolization increases the posttreatment tumor to non-tumor activity concentration ratio, compared with using a standard end-hole microcatheter.

Detailed Description

Study design: clinical within-subject randomized controlled trial.

Study population: 25 patients with unresectable, chemorefractory, liver-dominant colorectal liver metastases.

Intervention: scout and therapeutic doses of holmium-166 microspheres will be administered in the left and right hepatic artery during two sequential angiography procedures on the same day. In all subjects, the use of the Surefire Infusion System and the standard end-hole catheter will be randomly allocated to the infusion site (left and right hepatic artery).

Baseline and follow-up investigation: at baseline and during follow-up, patients will undergo physical examination and laboratory investigations for toxicity assessment, and a whole-body 18F-FDG-PET + dual-phase liver CT (at baseline and 3-months follow-up) for tumor response assessment. After the scout procedure and therapeutic procedure, a holmium-166 SPECT/CT will be obtained for the assessment of the microsphere distribution.

Main study parameters/endpoints:

The primary endpoint is the tumor to non-tumor activity concentration ratio on SPECT/CT.

Secondary endpoints include mean absorbed doses of radioactivity in tumorous and healthy liver tissue, tumor response, the predictive value of holmium-166 scout dose and infusion efficiency. These endpoints will be compared between the Surefire Infusion System and standard microcatheter infusions. A dose-response relationship, clinical toxicity and overall survival will be assessed for the entire cohort.

Study Timeline

• Study First Submitted: 2014-07-31
• Study First Submitted QC: 2014-08-04
• Study First Posted: 2014-08-05
• Study Start: 2014-11
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-07
• Last Update Posted: 2016-11-09
• Primary Completion: 2017-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 25

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

• World health organization performance score > 2
• Inadequate bone marrow function (hemoglobin < 6.0 mmol/l, leukocyte count < 3.0 x 109/l, platelet count < 75x 109/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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Standard End-hole Microcatheter	Holmium-166-poly (L-lactic acid) microspheres	Hepatic arterial administrations using the standard end-hole microcatheter
Surefire Infusion System	Holmium-166-poly (L-lactic acid) microspheres	Hepatic arterial administrations using the Surefire Infusion System

Primary Outcome Measures

Name	Time	Method
Posttreatment tumor to non-tumor activity concentration ratio on SPECT/CT	5 days after treatment

Secondary Outcome Measures

Name	Time	Method
Overall survival	From date of treatment until the date of death from any cause, assessed up to 1 year
Dose-response relationship between tumor absorbed doses on SPECT/CT and tumor response on CT and 18F-FDG-PET	3 months after treatment
Infusion efficiency	On the day of treatment	Defined as the percentage of calculated treatment activity that was administered
Clinical and laboratory toxicity	Up to 3 months after treatment	According to Common Terminology Criteria for Adverse Events version 4.03
Posttreatment tumor response on CT and 18F-FDG-PET	3 months after treatment
Mean absorbed radiation doses in tumorous and healthy liver tissue on SPECT/CT	5 days after treatment
Predictive value of the holmium-166 scout dose	On the day of treatment

Trial Locations

Locations (1)

Department of Radiology and Nuclear Medicine, University Medical Center Utrecht; 🇳🇱 Utrecht, Netherlands