DEBIRI Plus Chemotherapy vs. Chemotherapy Alone in Colorectal Cancer Liver Metastases (CLEAR-DEBIRI)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Metastatic; Liver Neoplasm
• Intervention / Treatment: Drug: Drug-Eluting Embolic Bead; Drug: Chemotherapy drug

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.

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Anahita Mirzasadeghi, MD; Phone Number: +989123193830; Email: Mirzasadeghianahita@gmail.com

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1419733141
    • Recruiting
    • Imam khomeini hospital complex
    • Contact: Anahita Mirzasadeghi; Phone Number: 00989123193830

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DEBIRI+ Chemotherapy +/- Targeted therapy; Patients will receive systemic chemotherapy on day 0 and 14 and DEBIRI on day 7 and 21.	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 (100 mg) eluted with a vial of beads(hepaSphere 25mg) is injected into the blood vessels feeding the tumor. The intervention will be repeated to deliver 200 mg of irinotecan intravascularly to the liver mass. A 14-day interval between the procedures is established to minimize side effects. Targeted therapy administration for each treatment group based on oncologist's decision and will be tailored to the tumor characteristics and the patient's clinical status as explained in control arm.; Other Names: Irinotecan-loaded drug-eluting beads (DEBIRI) plus systemic chemotherapy +/- targeted therapy
Active Comparator: Chemotherapy +/- Targeted therapy; Patients will receive 4 cycles of systemic chemotherapy.	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 mutations). Due to the targeted nature of these therapies, they can not be administered to all participants of the trial, while It is not ethically justifiable to withhold targeted therapies from patients who are candidates for these treatments based on their tumor characteristics and deprive them of potentially life-extending options.; Other Names: Systemic chemotherapy +/- targeted therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	The feasibility of secondary tumor resection after receiving treatment, based on follow up imaging and tumor downsizing, will be discussed in multidisciplinary meeting (including surgeons, radiologists and oncologists).	within 3 months after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event rate	Unfavorable and unintended signs and symptoms associated with the treatment.	Within 1 year of treatment administration

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Investigators: Principal Investigator: Ali Jafarian, MD, Tehran University of Medical Sciences, Tehran, Iran

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: August 5, 2024
• First Submitted That Met QC Criteria: August 12, 2024
• First Posted (Actual): August 15, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: survival; irinotecan; chemoembolization; colorectal liver metastases; irinotecan loaded drug-eluting beads TACE (DEBIRI-TACE)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Liver Diseases; Colonic Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Irinotecan
• Other Study ID Numbers: 72101-246-1-1403

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes