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
To evaluate the efficacy of Irinotecan-loaded drug-eluting beads (DEBIRI) administered concurrently with Systemic chemotherapy as first-line treatment in unresectable colorectal cancer liver metastases
Design
In this phase III clinical trial, a total of 116 patients who meet the inclusion criteria will be randomly assigned to either the intervention 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. Intervention group will recieve a minimum of 2 sessions of DEBIRI treatment and 2-4 cycles of systemic chemotherapy (based on pattern of liver involvement, response rate, tolerance, occurrence or absence of side effects, and liver function). Downsizing of the liver tumors will be assessed by RECIST criteria. The feasibility of secondary tumor resection will be reassessed at a three-month follow-up multidisciplinary team (MDT) meeting, guided by established guidelines.
Settings and conduct
Imam Khomeini hospital
Participants/Inclusion and exclusion criteria
Patients with unresectable/borderline resectable colorectal cancer liver metastases, aged 18 years or older and chemotherapy-naïve for metastatic disease will be enrolled. Adequate hematologic, hepatic, renal function and ECOG performance status of 2 or less are essential for enrolment.
Patients who are candidates for curative surgery without the need for neoadjuvant therapy, Liver involvement of ≥70%, brain metastases or Peritoneal carcinomatosis, History of an allergic reaction to any of the study drugs, Chronic viral hepatitis B or C, Cirrhosis and who are currently Pregnant or Breastfeeding, will be excluded.
Intervention groups
A minimum of 2 sessions of DEBIRI and 2-4 cycles of systemic chemotherapy will be administered
Main outcome variables
Conversion to resectability
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20240627062267N1
Registration date:2024-08-07, 1403/05/17
Registration timing:prospective
Last update:2024-08-07, 1403/05/17
Update count:0
Registration date
2024-08-07, 1403/05/17
Registrant information
Name
Anahita Mirzasadeghi
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 6119 0000
Email address
mirzasadeghianahita@gmail.com
Recruitment status
recruiting
Funding source
Expected recruitment start date
2024-08-22, 1403/06/01
Expected recruitment end date
2026-09-22, 1405/06/31
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific 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
Public title
Efficacy of DEBIRI in colorectal cancer liver metastases
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Patients with histologically proven, unresectable or borderline resectable liver metastases from colorectal origin, who are 18 years or older and
Patients who are chemotherapy-naïve for their metastatic disease
Metastases burden must be exclusively or predominantly limited to the liver.
Adequate hematologic, hepatic, and renal function ( ANC ≥ 1.5 × 10^9/L• PLT ≥ 75 × 10^9/L• INR ≤ 1.3• Total bilirubin ≤ 2.0 mg/dL• AST and ALT ≤ ×5 the upper limit of normal (ULN)• Albumin ≥ 2.5 g/dL• Creatinine ≤ 2.0 mg/dL)
Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
Exclusion criteria:
Patients who are candidates for curative surgery without the need for neoadjuvant therapy
Liver involvement of ≥ 70%
Presence of brain metastases
Peritoneal carcinomatosis
Presence or History of an allergic reaction to any of the study drugs
Chronic viral hepatitis B or C
Cirrhosis
Pregnancy (based on elevated serum or urine B-HCG level)
Breastfeeding
Patient’s refusal to participate in the study
Age
From 18 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
116
Randomization (investigator's opinion)
Randomized
Randomization description
A total of 116 patients who meet the inclusion criteria will be randomly assigned to either the treatment group (DEBIRI plus systemic chemotherapy) or the control group (systemic chemotherapy alone).
With the aim of controlling major confounding factors, reducing the potential for bias and to be ensured that both treatment groups have a similar distribution of patients with synchronous/metachronous metastases and resectable/borderline resectable tumors, Stratified randomization will be performed based on synchronous/metachronous liver metastases and unresectable/borderline resectable status. Patients then will be divided into 4 strata based on the combination of synchronous, unresectable; synchronous, borderline resectable; metachronous, unresectable; metachronous, borderline resectable. Within each stratum, patients are randomly assigned to either the treatment or control group.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Patient reassessment to evaluate treatment response as primary endpoint, will be performed using MRI or CT scan within 1-3 months of treatment initiation. All Imaging will be reviewed by two radiologists who are blinded to clinical information regarding treatment arm.
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
TUMS research ethics committe
Street address
Secretariat of the Ethics Committee in Biomedical Research at Tehran University - Keshavarz Boulevard - Qods Street Intersection - Central Building of Tehran University of Medical Sciences - 6th Floor - Room 604.
City
Tehran
Province
Tehran
Postal code
1417653761
Approval date
2024-06-23, 1403/04/03
Ethics committee reference number
IR.TUMS.IKHC.REC.1403.120
Health conditions studied
1
Description of health condition studied
Colorectal cancer liver metastases
ICD-10 code
C78.7
ICD-10 code description
Secondary malignant neoplasm of liver and intrahepatic bile duct
2
Description of health condition studied
Colorectal cancer liver metastases
ICD-10 code
C18
ICD-10 code description
Malignant neoplasm of colon
3
Description of health condition studied
Colorectal cancer liver metastases
ICD-10 code
C20
ICD-10 code description
Malignant neoplasm of rectum
Primary outcomes
1
Description
Conversion to resectability
Timepoint
Tumor downsizing will be evaluated within three months of treatment initiation.
Method of measurement
Downsizing of the liver tumors will be assessed by RECIST criteria. The feasibility of secondary tumor resection will be reassessed at a three-month follow-up multidisciplinary team (MDT) meeting, guided by established clinical guidelines.
Secondary outcomes
1
Description
Adverse event rate
Timepoint
upon treatment initiation till last follow up.
Method of measurement
Common Terminology Criteria for Adverse Events (CTCAE)
Intervention groups
1
Description
Intervention group: For the intervention group, a minimum of 2 sessions of DEBIRI treatment and 2 to 4 cycles of systemic chemotherapy are administered (based on tumor size, bilobar or unilobar involvement of the liver, treatment response rate, treatment tolerance, occurrence or absence of side effects, and liver function). Prior to performing DEBIRI, initial angiography is done using the master parkway HFKIT ASAHI catheter 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 with the goal of delivering 200 mg of irinotecan intravascularly to the liver mass. A 14-day interval between the two procedures is established to minimize DEBIRI-related side effects. Targeted therapy administration for each treatment group based on oncologist's decision and will be tailored to the tumor's biological characteristics and the patient's clinical status.
Category
Treatment - Other
2
Description
Control group: patients in 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's biological characteristics and the patient's clinical status.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Imam Khomeini Hospital Complex
Full name of responsible person
Dr. Ali Jafarian
Street address
End of Keshavarz Blvd.
City
Tehran
Province
Tehran
Postal code
1419733141
Phone
+98 21 6119
Fax
Email
mirzasadeghianahita@gmail.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr. Ali Akbari Sari
Street address
School of Medicine, Pour Sina St., Qods St.
City
Tehran
Province
Tehran
Postal code
1461884513
Phone
+98 21 6641 8466
Email
vcr@sina.tums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
No
Title of funding source
Tehran university of medical science
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Anahita Mirzasadeghi
Position
Hepatopancreatobiliary surgery fellow
Latest degree
Specialist
Other areas of specialty/work
General Surgery
Street address
Imam Khomeini Hospital Complex, End of Keshavarz Blvd.
City
Tehran
Province
Tehran
Postal code
1419733141
Phone
+98 21 6119 0000
Fax
Email
mirzasadeghianahita@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Anahita Mirzasadeghi
Position
Hepatopancreatobiliary surgery fellow
Latest degree
Specialist
Other areas of specialty/work
General Surgery
Street address
Imam Khomeini Hospital Complex, End of Keshavarz Blvd.
City
Tehran
Province
Tehran
Postal code
1419733141
Phone
+98 21 6119 0000
Fax
Email
mirzasadeghianahita@gmail.com
Person responsible for updating data
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Anahita Mirzasadeghi
Position
Hepatopancreatobiliary surgery fellow
Latest degree
Specialist
Other areas of specialty/work
General Surgery
Street address
Imam Khomeini Hospital Complex, End of Keshavarz Blvd.
City
Tehran
Province
Tehran
Postal code
1419733141
Phone
+98 21 6119 0000
Fax
Email
mirzasadeghianahita@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Yes - There is a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
Title and more details about the data/document
The patient’s data including baseline characteristics, the initial size and location of the liver metastases, type of treatment received by the patient, and treatment outcomes based on the RECIST criteria, will be published in reputable scientific journals as an article.
When the data will become available and for how long
6 months after completing the study and performing statistical analysis, the data will be published.
To whom data/document is available
The raw and anonymized patient data, each associated with a unique code for every patient, will be made available to colleagues involved in the study and statistical consultants. After publishing the data and research results, The report will be accessible to the public in the form of a scientific article.
Under which criteria data/document could be used
Ethics experts in research will also have access to research information.
From where data/document is obtainable
Liver Transplant Research Center, Imam Khomeini Hospital
What processes are involved for a request to access data/document
The requester can send their request to the email address mirzasadeghianahita@gmail.com, and after reviewing the request, according to the discretion of the principal investigator, Dr. Ali Jafarian, information will be provided in an unidentifiable form.