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

N/ANot Yet RecruitingNCT07406126

Fernando Gómez Muñoz30 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Colorectal Liver Metastases (CRCLM)Unresectable Colorectal Liver Metastases

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically confirmed primary adenocarcinoma of the colon or rectum * Potentially resectable colorectal liver metastases, with limiting factors for resection including: 1. Insufficient future liver remnant. 2. 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) * Patient should match standard 90Y radioembolization inclusion criteria: 1. Signed informed consent; 2. Age ≥ 18 years; 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1; 4. Life expectancy of ≥ 3 months; 5. 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 Exclusion Criteria: * 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 * Severe portal hypertension * Second primary malignancy within the past 5 years, other that adequately treated non-melanoma skin cancer, carcinoma in situ of any organ or second primary colorectal cancer * Unresectable primary tumor in situ; * Other serious comorbidity or any other condition, that renders patients unsuitable for the study treatment * Pregnancy, lactation or refusal to use adequate contraceptive measures * History of allergic reaction to any components of the treatment that cannot be medically corrected.

Outcomes

Primary Outcomes

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.