DEBIRI Plus Chemotherapy vs. Chemotherapy Alone in Colorectal Cancer Liver Metastases

Official title

Comparative Analysis of the Efficacy of Irinotecan-loaded Drug-eluting Beads (DEBIRI) in Combination With Systemic Chemotherapy Versus Chemotherapy Alone in Unresectable Colorectal Cancer Liver Metastases: a Randomized Clinical Trial

Overview

A total of 116 patients who meet the inclusion criteria and are chemotherapy-naïve for their metastatic disease, will be randomly assigned to either the treatment group (DEBIRI plus systemic chemotherapy) or the control group (systemic chemotherapy alone). After 4 cycles of chemotherapy and 2 cycles of DEBIRI, patient reassessment to evaluate treatment response, based on RECIST criteria, will be performed using MRI or CT scan within 1-3 months of treatment initiation. The feasibility of secondary tumor resection, as primary endpoint, will be reassessed at a three-month follow-up multidisciplinary team (MDT) meeting, guided by established clinical guidelines.

Detailed description

Upon acquiring ethical approval, patients with histologically proven, unresectable or borderline resectable liver metastases from colorectal origin who are referred to the hepatobiliary clinic between September 2024 and September 2026 will be enrolled to the study. Informed consent will be obtained for their participation prior to enrollment.

A total of 116 patients who are chemotherapy-naïve for their metastatic disease, will be randomly assigned to either the treatment group or the control group.

With the aim of controlling major confounding factors, Stratified randomization will be performed based on synchronous/metachronous liver metastases and unresectable/borderline resectable status.

Targeted therapy administration for each treatment group in based on oncologist's decision and will be tailored to the tumor's biological characteristics and the patient's clinical status. Ultimately, patients will be categorized into one of the two following treatment groups:

Group 1: DEBIRI+ standard systemic chemotherapy ± Targeted therapy Group 2: Standard systemic chemotherapy ± Targeted therapy The Tumor characteristics, including the number, size, and anatomical location, as well as the presence or absence of extrahepatic metastases, will be assessed based on initial imaging (MRI).

The treatment protocol is defined as the administration of a chemotherapy regimen on days 0 and 14, followed by DEBIRI on days 7 and 21. Each patient of the treatment arm will receive at least two doses of DEBIRI unless treatment-limiting adverse events occur.

After 4 cycles of chemotherapy and 2 cycles of DEBIRI, patient reassessment to evaluate treatment response will be performed using MRI or CT scan within 1-3 months of treatment initiation. All imagings will be reviewed by 2 radiologists who are blinded to clinical information regarding treatment arm. Treatment response will be determined using RECIST criteria.

Conversion to resectability, as primary endpoint, will be evaluated at a three-month follow-up multidisciplinary team (MDT) meeting, guided by established clinical guidelines.

Secondary endpoints of the study will encompass evaluation of treatment tolerability and adverse event rate, alongside analyzing progression-free survival and overall survival.

Interventions

• Drug Drug-Eluting Embolic Bead
  A minimum of 2 sessions of DEBIRI treatment and 2-4 cycles of systemic chemotherapy are administered (based on tumor size, bilobar or unilobar involvement of the liver, treatment response rate, treatment tolerance, occurrence of side effects, and liver function). Prior to performing DEBIRI, initial angiography is done via the femoral or axillary artery to determine the anatomy of the right and left hepatic arteries as well as the arteries supplying the tumor. Subsequently, a vial of irinotecan (
• Drug Chemotherapy drug
  Control group will receive 2-4 cycles of systemic chemotherapy based on functional status of the patient, adverse event rate and treatment tolerance, tumor size and characteristics. Targeted therapy administration for each treatment group in based on oncologist's decision and will be tailored to the tumor characteristics and the patient's clinical status (e.g., administration of Pembrolizumab for patients with high rosatellite instability (MSI-H) or Bevacizumab for tumors harboring KRAS mutation

Primary outcome measures

• Conversion to resectability: The proportion of patients who were initially deemed unresectable but, after undergoing specific intervention (Based on study arm) are reassessed for tumor shrinkage and found to be candidates for surgical resection. [Time frame: within 3 months after treatment initiation]

Secondary outcome measures (1)

• Adverse event rate [Time frame: Within 1 year of treatment administration]

Eligibility criteria

Inclusion criteria

• unresectable/borderline resectable colorectal cancer liver metastases, chemotherapy-naïve for metastatic disease, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less adequate hematologic, hepatic, and renal function ( absolute neutrophil count ≥ 1.5 × 10\^9/L, platelet ≥ 75 ×10\^9/L, international normalized ratio ≤ 1.3, Total bilirubin ≤ 2.0 mg/dL, aspartate aminotransferase and alanine aminotransferase ≤ 5 × the upper limit of normal (ULN), Albumin ≥ 2.5 g/dL, Creatinine ≤ 2.0 mg/dL)

Exclusion criteria

• candidates for curative surgery without the need for neoadjuvant therapy, Liver involvement of ≥ 70%, brain metastases or Peritoneal carcinomatosis, cirrhosis, presence or History of an allergic reaction to any of the study drugs Chronic viral hepatitis B or C

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Iran · 1 center

• Imam khomeini hospital complex — Tehran

Identifiers

NCT: NCT06555003 · 72101-246-1-1403

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗