Yttrium-90 Radioembolization Neoadjuvant Therapy With Immune Marker Profiling and Dosimetry for Potentially Resectable Patients With Colorectal Liver Metastases

NCT07406126 | Not Yet Recruiting

• 1 other identifier: GIBI2^30- YRENE
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

This is a observational, prospective, single arm, proof of concept study to assess safety, feasibility, and potential efficacy of combining Yttrium-90 transarterial radioembolization(TARE) with standard systemic therapy in clinical practice for potentially resectable patients with colorectal liver metastases (CRLM). Alternatively, resectability will also be evaluated. The investigators hypothesize that by applying this approach, higher local control and resection rates can be achieved (typically below 13% for patients who are initially deemed unresectable). Additionally, this treatment option is expected to help delay or reduce the need for (a switch in) systemic treatment and eventually improve survival in patients with liver metastases that are not resectable. All studies reporting the results of TARE at ablative doses are retrospective cohort studies or cases series. Prospective data is needed to expand the indications and reimbursement of radioembolization. Other objectives of the study are:

• To calculate the resection rate in patients undergoing the combined approach.
• To evaluate immune markers in peripheral blood and resected metastases.
• To formulate the first concept of an algorithm, enable to deliver personalized AI assisted dosimetry.
• To assess potential role of circulating tumor DNA (ctDNA) in evaluation of patient prognosis and follow up.
• To determine the grade of necrosis at the time of resection and correlate with the absorbed dose.

Conditions

Colorectal Liver Metastases (CRCLM); Unresectable Colorectal Liver Metastases

Keywords

Unresectable Colorectal Liver Metastases; Potentially resectable patient; neoadjuvant therapy; Immune Marker Profiling; circulating tumor DNA; personalized dosimetry approach; Insufficient future liver remnant; Observational; multicenter; prospective; YRENE; TARE; TheraSphere®; Yttrium-90; Transarterial Radioembolization; primary colon adenocarcinoma; primary rectum adenocarcinoma; Unfavourable tumor location; metastatic disease; FOLFOX 6

Outcome Measures

Primary Outcomes (8)

• Monitoring for adverse events related to the procedure.

  Evaluate the safety of combining neoadjuvant ablative dose 90Y radioembolization with standard systemic therapy in patients with CRLM. Safety assessments will include monitoring for adverse events related to the procedure.

  From 90Y radioembolization (week 2-4) to the end of study at 30 weeks

• Evaluate the safety related to the procedure by measuring changes in Liver function values in blood.

  To evaluate hepatic safety after neoadjuvant ablative-dose Yttrium-90 radioembolization combined with standard systemic therapy in patients with CRLM changes in laboratory biomarkers will be compared with baseline values and subsequent assessments. Biomarkers and Units of Measure: \- Liver Function Markers: Bilirubin (mg/dL), Albumin (g/dL), Aspartate Aminotransferase (AST) (U/L), Alanine Aminotransferase (ALT) (U/L), Gamma-Glutamyl Transferase (GGT) (U/L), Alkaline Phosphatase (FA) (U/L), Cholinesterase (ChE) (U/L), Lactate Dehydrogenase (LDH) (U/L)

  From 90Y radioembolization (week 2-4) to the end of study at 30 weeks

• Evaluate the safety related to the procedure by measuring changes in Liver function values in blood.

  To evaluate hepatic safety after neoadjuvant ablative-dose Yttrium-90 radioembolization combined with standard systemic therapy in patients with CRLM changes in laboratory biomarkers will be compared with baseline values and subsequent assessments. Biomarkers and Units of Measure: Inflammatory Marker: C-reactive protein (CRP) (mg/L) Renal Function Marker: Creatinine (mg/dL)

  From 90Y radioembolization (week 2-4) to the end of study at 30 weeks

• Evaluate the safety related to the procedure by measuring changes in Liver function values in blood.

  To evaluate hepatic safety after neoadjuvant ablative-dose Yttrium-90 radioembolization combined with standard systemic therapy in patients with CRLM changes in laboratory biomarkers will be compared with baseline values and subsequent assessments. Biomarkers and Units of Measure: Composite Liver Function Scores: Albumin-Bilirubin (ALBI) score (unitless), Albumin-Bilirubin (ALBI) grade (ordinal scale)

  From 90Y radioembolization (week 2-4) to the end of study at 30 weeks

• Evaluate the safety related to the procedure by measuring changes in tumor markers in blood.

  Evaluate the safety of combining neoadjuvant ablative dose 90Y radioembolization with standard systemic therapy in patients with CRLM by assessing tumor markers in blood: Carcinoembryonic antigen (CEA) and CA 19-9.

  From 90Y radioembolization (week 2-4) to the end of study at 30 weeks

• Evaluate the quality of Life After Liver Resection Assessed by FACT-C (Version 4) Following 90Y Radioembolization

  Evaluate the safety of combining neoadjuvant ablative dose 90Y radioembolization with standard systemic therapy in patients with CRLM. Safety assessments will include assessing overall well-being of the patients focus on quality of life after liver resection. Outcome Measure: Change in Functional Assessment of Cancer Therapy-Colorectal (FACT-C, Version 4) total score from baseline to 30 weeks. The FACT-C (Version 4) total score and each subscale will be analyzed as independent measures to evaluate longitudinal changes in overall well-being and postoperative recovery after liver resection, characterizing treatment-related safety and tolerability. Quality-of-Life Instrument: Functional Assessment of Cancer Therapy-Colorectal (FACT-C, Version 4): Total score and subscale scores (Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, and Colorectal Cancer Subscale), reported according to standard scoring guidelines.

  From 90Y radioembolization (week 2-4) to the end of study at 30 weeks

• Evaluate the efficacy of the procedure by tumor response rate assessed by means of RECIST 1.1

  Efficacy assessments will include tumor response rate assessed by means of RECIST 1.1. Baseline efficacy imaging scans will be conducted during the screening phase. Efficacy assessment scans will follow standard-of-care clinical management guidelines, occurring every 8 weeks (with a variance of +/- 1 week) post-inclusion until resection or until progression.

  From week 0 to resection, progression or week 26-28

• Evaluate the efficacy of the procedure: pathologic response assessment on the resected specimens.

  Efficacy assessments will include tumor response rate assessed by means of RECIST 1.1. It will be of capital interest the pathologic response assessment on the resected specimens.

  From week 0 to resection, progression or week 26-28

Secondary Outcomes (9)

• Resection rate in patients undergoing the combined approach

  week 18-20 and week 26-28

• Cellular population quantification on peripheral blood samples: leukocytes, neutrophils, lymphocytes, monocytes, eosinophils and basophils.

  Week 0, 6, 8 and 16

• Inflammatory interleukines IL-6, IL-10 and IFN-γ quantification:

  Week 0, 6, 8 and 16

• Intratumoral T Cells Infiltration in biopsies and resected tumors.

  week 0, week 18/20 and week 26/28

• PERSONALIZED AI ASSISTED DOSIMETRY evaluation

  week 0 to 26-28

Interventions

Yttrium-90 Radioembolization with standard systemic therapy PROCEDURE

Yttrium-90 microspheres are administered through the hepatic artery which supplies blood to tumor tissue (the portal vein supplies blood to the normal hepatic tissue). The microspheres are trapped in the vasculature of the tumor due to arteriolar capillary blockage where they exert a local radiotherapeutic effect. In clinical use, the glass microspheres remain permanently trapped in the vasculature where the isotope decays to infinity leaving background radiation with no therapeutic value. This procedure is combined with standard systemic therapy per routine clinical practice.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients (N = 30) with insufficient FLR and patients with unfavorable lesion location, size and/ or number, requiring downsizing of metastases in order to achieve R0 resection will be discussed at the respective local multidisciplinary teams (MDT) meetings. Patients can be included if they are found suitable for TARE and surgery based on a liver MRI, contrast enhanced CT or PET-CT and clinical and laboratory results. Patients are allowed to undergo other local liver treatments (e.g. ablation) in combination with TARE, as long as all liver metastasis are locally treated to achieve R0 resection. Patients are not allowed to use systemic chemotherapy two weeks prior and two weeks post TARE. Target therapies have to be stopped at least 4 weeks prior to TARE.

You may qualify if:

• Histologically confirmed primary adenocarcinoma of the colon or rectum
• Potentially resectable colorectal liver metastases, with limiting factors for resection including:
• Insufficient future liver remnant.
• Unfavorable tumor location (e.g. involvement of a major vessel and/or bile duct)/ large size and/ or number of lesions, which limit resection with R0 margins and requires downsizing of the metastases
• No or limited extrahepatic metastatic disease (limited extrahepatic disease should be amenable to eradicate with locoregional therapies as per multidisciplinary discussion of surgeons, radiation oncologists and interventional radiologists)
• Signed informed consent;
• Age ≥ 18 years;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
• Life expectancy of ≥ 3 months;
• Measurable target tumors in the liver according to RECIST 1.1
• Laboratory parameters: eGFR \>45/mL/min/1.73 m2; albumin \> 3.0 g/dl, normal bilirubin (unless Gilbert syndrome); aminotransferase (ALAT/ASAT) \<3.0 ULN

You may not qualify if:

• Life expectancy ≤3 months
• Patient initially eligible for surgery or thermal ablation of the liver metastases
• Progressive extra-hepatic disease
• Active extra-hepatic disease that cannot be treated
• Life-threatening extra-hepatic disease (i.e. dialysis, unresolved diarrhea, serious unresolved infections (HIV, HBV, HCV etc.))
• Uncorrectable coagulopathy
• Contraindication for angiography or MRI
• Significant toxicities due to prior cancer therapy that have not resolved before the initiation of the study; if the investigator determines that the continuing complication will compromise the safe treatment of the patient
• Any surgical contraindication
• Ascites
• Expected difficulties for safe execution of TARE based on pretreatment Tc99m-MAA imaging, including;
• Flow to extra-hepatic vessels not correctable by reposition of catheter or embolization Uncorrectable estimated dose to the lungs \>30Gy in a single administration or \>50Gy cumulatively
• Uncorrectable estimated dose to the untreated liver of \>70Gy
• Estimated average dose to the viable tumor volume \<200Gy
• Prior liver radiotherapy

Sponsors & Collaborators

• Fernando Gómez Muñoz: lead
• Instituto de Investigacion Sanitaria La Fe: collaborator
• Boston Scientific International S.A.: collaborator

Study Sites (5)

Hospital Universitario de Navarra

Pamplona, Navarre, Spain

Location

Hospital Provincial de Castellón

Castelló, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Hospital Universitario y Politécnico la Fe

Valencia, Spain

Location

Related Publications (6)

• Alsultan AA, et al. Dose-Response and Dose-Toxicity Relationships for Glass 90Y Radioembolization in Patients with Liver Metastases from Colorectal Cancer. J Nucl Med. 2021 Nov;62(11):1616-1623.

  BACKGROUND

• Mulcahy MF. et al. EPOCH Investigators. Radioembolization With Chemotherapy for Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase III Trial. J Clin Oncol. Dec 10;39(35):3897-3907 (2021).

  BACKGROUND

• Torkian P. et al. Cancer Immunology: Impact of Radioembolization of Hepatocellular Carcinoma on Immune Response Modulation. AJR Am J Roentgenol. Jun;220(6):863-872 (2023)

  BACKGROUND

• Garin E, et al. DOSISPHERE-01 Study Group. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial. Lancet Gastroenterol Hepatol. Jan;6(1):17-29 (2021).

  BACKGROUND

• Simmonds, P. C. et al. Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies. British journal of cancer 94, 982-999, doi:10.1038/sj.bjc.6603033 (2006).

  BACKGROUND

• De Greef, K. et al. Multisciplinary management of patients with liver metastasis from colorectal cancer. World journal of gastroenterology 22, 7215-7225, doi:10.3748/wjg.v22.i32.7215 (2016)

  BACKGROUND

Related Links

• American Cancer Society. Key Statistics for Colorectal Cancer.

Biospecimen

Retention: SAMPLES WITH DNA

Blood and tissue samples

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Fernando Gómez, MD PhD

CONTACT

+34 628281300; gomez_fermun@gva.es

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, MD, PhD

Study Record Dates

• First Submitted: December 4, 2025
• First Posted: February 12, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be available after publication for a period of 5 years.
• Access Criteria: Qualified researchers upon reasonable request directed to GIBI230@iislafe.es.

Locations

ES (5)