Selective Internal Radiation Therapy With 90Y Resin Micropheres for Refractory Colorectal Cancer Liver Metastases (SIRT)

Selective Internal Radiation Therapy With 90Y Resin Micropheres for Refractory Colorectal Cancer Liver Metastases - SIRT - A Translational Feasibility Study

Observational, feasibility study investigating biological aspects in patients with liver metastasis from colorectal cancer undergoing treatment with SIRT, by translational analysis of biological samples.

Study Overview

• Status: Recruiting
• Conditions: Liver Metastasis Colon Cancer

Detailed Description

In this study, the investigators seek to investigate biological aspects in patients with colorectal cancer liver metastasis undergoing treatment with Selective Internal Radiation Therapy, by translational analysis of biological samples.

SIRT will be conducted as per standard procedure at Aarhus University Hospital. Translational blood samples will be drawn pre-treatment and during follow up.

The total cell free DNA level will be quantified in all samples. The samples will be analysed for tumour specific mutations such as the KRAS, BRAF and NRAS oncogenes.

The investigators expect to include up to 30 patients.

This is a purely observational translational study. Results will be analysed in relation to outcome data.

The study is conducted in collaboration with:

Department of Gastroenterology and Hepatology, Aarhus University Hospital Department of Radiology, Aarhus University Hospital Department of Nuclear Medicine, Aarhus University Hospital

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Louise B Callesen, MD; Phone Number: +4578462535; Email: louicall@rm.dk

Study Locations

• Denmark
  • Danmark
    • Aarhus N, Danmark, Denmark, 8200
      • Recruiting
      • Department of Oncology, Aarhus University Hospital
      • Contact: Louise B Callesen, MD; Phone Number: 30482884; Email: louicall@rm.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients with metastatic colorectal cancer with chemorefractory liver dominant disease. Patients are found not eligible for surgical resection, RFA or SBRT by a multidisciplinary tumour board (MDT), and considered candidates for SIRT treatment in order to obtain disease control or resectability.

Description

Inclusion Criteria:

• Diagnosis of metastatic colorectal adenocarcinoma with liver dominant disease
• Diagnosis of liver metastasis may be made by histo- or cyto-pathology, or by clinical and imaging criteria.
• The Liver metastasis are not eligible for resection, RFA or SBRT
• All patients must be off all chemotherapeutic regimens for 14 days prior to SIRT treatment
• All patients must be off vascular endothelial growth factor inhibitors for 6 weeks prior to SIRT treatment
• Progressive disease, severe intolerance during or following all standard lines of chemo-therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Age 18 years or older
• Able to understand written information
• Consent to samples for translational research

Exclusion Criteria:

• Pretherapeutic work-up procedure with Tc-99m macroaggregated albumin (MAA) scintigraphy showing extrahepatic foci in GI-tract
• Evidence of any detectable Tc-99m macroaggregated albumin deposition in the stomach or duodenum, after application of established angiographic techniques to stop such deposition
• Previous radiation therapy to the lungs and/or to the upper abdomen overlapping with dose to the liver at interventionist´s decision
• Lung shunt greater than 20% or > 30 Gray radiation absorbed dose to the lungs, at estimated by Tc-99m-MAA
• Pregnancy
• Symptomatic lung disease precluding SIRT at interventionist´s decision
• Active uncontrolled infection
• Any pre-treatment laboratory findings within 30 days of treatment demonstrating: alanine aminotransferase level greater than 5 times upper normal limit and/or serum bilirubin greater than 2 mg/dl (>34 umol/l)
• Current or previously evidence of ascites on CT-scan or physical examination
• Tumour volume greater than 50% of liver volume
• Conditions precluding translational samples

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility and translational analysis	Investigating potential prognostic and predictive markers for efficacy by molecular characteristics and mutational analysis	When 5 patients are included, the blood samples will be analysed for explorative analysis (expected after the first year). In all we expect to include 30 patients if positive results.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		3 years
Progression Free Survival		3 years
Response Rate	According to RECIST 1.1	6 months

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Investigators: Principal Investigator: Louise B Callesen, Experimental Clinical Oncology

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Estimated): February 28, 2026
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (Actual): July 30, 2020

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Selective Internal Radiation Therapy; Liver metastasis Colon Cancer; Circulating Tumour DNA
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: 1-10-72-111-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No