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

Study Overview
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Brief Summary
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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.

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

Conditions
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Colorectal Cancer Liver Metastases, Regorafenib

Intervention / Treatment
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* Drug: Regorafenib and DIBIRI
* Drug: Regorafenib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Irinotecan Drug-Eluting Beads combined with regorafenib<br> | Drug: Regorafenib and DIBIRI<br>* 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.<br>* Other names: Device: drug eluting-bead;|
| Active Comparator: regorafenib<br> | Drug: Regorafenib<br>* Drug: Regorafenib Regorafenib will be given 3 weeks on/1 week off (initial dose: 80 mg od po.)<br>|

What is the study measuring?
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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 |