Regorafenib Combined With Irinotecan Drug-Eluting Beads for Colorectal Cancer Liver Metastases (RIDER)

Regorafenib Combined With Irinotecan Drug-Eluting Beads as Third-line Treatment for Colorectal Cancer Liver Metastases: a Multicentre, Randomised Phase 3 Trial (RIDER)

This study is a multicentre, prospective, randomised trial, aims to evaluate the efficacy and safety of Irinotecan Drug-Eluting Beads combined with regorafenib as the third-line treatment for a patient with colorectal cancer liver metastases. The study is planned to enrolled 126 patients failing first- and second-line standard chemotherapy treatment.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer Liver Metastases; Regorafenib
• Intervention / Treatment: Drug: Regorafenib and DIBIRI; Drug: Regorafenib

• Study Type: Interventional
• Enrollment (Anticipated): 126
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Bo Zhang, M.D; Phone Number: 86-13660397903; Email: zhangb28@mail.sysu.edu.cn
• Study Contact Backup: Name: Bo Zhang, M.D

Study Locations

• China
  • Guangzhou
    • Guangdong, Guangzhou, China
      • Recruiting
      • Bo Zhang
      • Contact: Bo Zhang, M.D; Phone Number: +8613660397903; Email: zhangb28@mail.sysu.edu.cn
      • Contact: Bo Zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients over 18 years of age, of any race or sex, who have histologic or radiologic proof of colorectal cancer to the liver, who are able to give informed consent, will be eligible.
• Patients failing first- and second-line standard systemic chemotherapy.
• Patients with at least one measurable liver metastases, with size > 1cm response evaluation criteria in solid tumors (RECIST)
• Patients with liver dominant disease defined as ≥80% tumor body burden confined to the liver
• Less than 60% liver tumor replacement
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of < 2
• Child-pugh's grade A or B
• Life expectancy of > 3 months
• Non-pregnant with an acceptable contraception in premenopausal women.
• Hematologic function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, white cell count (WBC) ≥ 3.0 x 109/L, platelets ≥75 x109/L, international normalized ratio (INR) ≤1.3.
• Adequate hepatic and renal function: Alanine aminotransferase (ALT) or aspartate aminotransferase ≤2.5×above upper normal range, total bilirubin≤1.5×above upper normal range, Serum creatinine≤1.5×above upper normal range
• Women of child bearing potential and fertile men are required to use effective contraception negative serum beta human chorionic gonadotropin (βHCG)
• Signed, written informed consent

Exclusion Criteria:

• Prior treatment with TACE, regorafenib or fruquintinib
• Patients with brain metastases
• With serious heart, kidney, bone marrow, or lung, central nervous system diseases.
• Patients suffered with other cancer.
• patients who were seriously ill and had history of chronic disease such as tuberculosis (TB) and human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were excluded from the study.
• known or suspected history of allergy to any of the related drugs used in the study
• Women who are pregnant or breast feeding
• Patients with serious somatic or psychiatric illness regarded as contraindications or in need of treatment that would interfere with study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Irinotecan Drug-Eluting Beads combined with regorafenib	Drug: Regorafenib and DIBIRI; Drug: Regorafenib Regorafenib will be given 3 weeks on/1 week off (initial dose: 80 mg od po.) Drug: Irinotecan it will be mixed in eluting-beads and injected in the tumor. Procedure: TACE Transcatheter arterial chemoembolization（TACE）is a minimally invasive procedure performed to decrease the tumor's blood supply. Device: drug eluting-bead The eluting-bead,loaded with irinotecan (DEBIRI) to treat patients with hepatic metastases from colorectal cancer.; Other Names: Drug: Irinotecan; Procedure: TACE; Device: drug eluting-bead
Active Comparator: regorafenib	Drug: Regorafenib; Drug: Regorafenib Regorafenib will be given 3 weeks on/1 week off (initial dose: 80 mg od po.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	The PFS is defined as the time from the start of treatment to the date of first documented PD or death as a result of any cause, whichever occurred first. When a patient was alive and without progression, PFS was censored at the date of the last disease assessment.	24 months
Objective Response Rate (ORR)	The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR)	24 months
Disease Control Rate (DCR)	DCR is defined as the percentage of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating)	24 months
Duration of response (DOR)	It was defined as the time from the first judgment of complete remission (CR) or partial remission (PR) to the discovery of disease progression (PD) after treatment	24 months
Adverse enents	Safety variables will be summarized using descriptive statistics based on adverse events collection	24 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Director: Bo Zhang, M.D, Sixth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): June 10, 2023
• Primary Completion (Anticipated): March 31, 2027
• Study Completion (Anticipated): March 31, 2028

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: March 20, 2023
• First Posted (Actual): April 3, 2023

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan
• Other Study ID Numbers: SYSU-IC-01

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: No
• Studies a U.S. FDA-regulated device product: No