Liposomal Irinotecan and Leucovorin/5-fluorouracil Plus Bevacizumab in Metastatic Colorectal Cancer

Liposomal Irinotecan + Leucovorin + 5-fluorouracil + Bevacizumab as Second-line Therapy in Metastatic Colorectal Cancer (IRIS)：a Multicenter, Single-arm, Prospective, Phase II Study

This is a multi-center, single-arm study to investigate the efficacy and safety of liposomal irinotecan+5-FU/LV+ bevacizumab as second-line therapy in metastatic colorectal cancer in Chinese population.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: liposomal irinotecan; Drug: 5-FU; Drug: LV; Drug: Bevacizumab

Detailed Description

Colorectal cancer (CRC) has a poor prognosis and poses a serious threat to human health. FOLFIRI (irinotecan+5-FU/LV) / FOLFOX (oxaliplatin+5-FU/LV) ± angiogenesis inhibitors are common treatments for advanced CRC. For patients receiving oxaliplatin-based therapy, irinotecan-based therapy is recommended as second-line therapy. Liposomal irinotecan is a new pharmaceutical form of traditional irinotecan. It adopts a special loading technology to encapsulate traditional irinotecan in liposomes, which can avoid its hydrolysis under physiological conditions, increase the affinity with cancer cells, overcome drug resistance, increase the drug uptake by cancer cells, reduce the drug dose, improve the efficacy and reduce the toxic side effects. The aim of this study is to explore the efficacy and safety of liposomal irinotecan+5-FU/LV + bevacizumab as second-line treatment for metastatic CRC.

• Study Type: Interventional
• Enrollment (Estimated): 173
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xuhua Hu, Doctor; Phone Number: 0311-86095347; Email: huxvhua@126.com

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • Recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Xuhua Hu; Phone Number: 031186095347; Email: wangguiying@hebmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age: 18-75 years old.
• Histologically or cytologically proven colon or rectum adenocarcinoma.
• Confirmed as unresectable metastatic disease through radiological examination.
• At least one measurable lesion (according to RECIST v1.1).
• First-line treatment with oxaliplatin-based therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 ~ 2.
• The expected survival time ≥3 months.
• Subject has adequate biological parameters as demonstrated by the following: absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count ≥100×10^9/L, hemoglobin (Hgb) ≥90 g/L, white blood cell (WBC)≥3.0×10^9/L.
• Adequate hepatic function as evidenced by total bilirubin ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) ≤2.5 x ULN, ≤5 x ULN if liver metastases are present.
• Adequate renal function as evidenced by serum creatinine (Cr)≤1.5 x ULN or creatinine clearance ≥60 mL/min, proteinuria <2+.
• Normal coagulation function (INR≤1.5).
• Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening.

Exclusion Criteria:

• Any other malignancy within 5 years prior to randomization, with the exception of cured in-situ carcinoma or basal cell carcinoma.
• Previous treatment with irinotecan/liposomal irinotecan.
• MSI-H/dMMR
• Massive pleural effusion or ascites requiring intervention.
• Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment.
• Active HIV, HBV, HCV infection.
• Combined with uncontrollable systemic diseases.
• Presence of severe gastrointestinal disease (including active bleeding, > grade 1 obstruction , > grade 1 diarrhea or gastrointestinal perforation)
• History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrolment.
• Presence of interstitial pneumonia or pulmonary fibrosis.
• Allergy to or intolerance to therapeutic drugs or their excipients;.
• History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within one month prior to enrollment.
• Presence of arterial embolism, severe bleeding (excluding bleeding caused by surgery) or tendency for existing embolism or severe bleeding within 6 months before enrollment.
• Patients with symptomatic central nervous system metastases.
• Documented serum albumin ≤3 g/dL
• Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1.
• Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception.
• Participated in other trial within 30 days prior to the first dose of study treatment.
• Patients who had received any intravenous antineoplastic therapy within 28 days or oral antineoplastic therapy within 14 days before the first dose of study drug
• Patients who are not suitable to participate in this trial for any reason judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; liposomal irinotecan+5-FU/LV+ bevacizumab q2w	Drug: liposomal irinotecan; liposomal irinotecan 70 mg/m²; Other Names: nal-IRI; Drug: 5-FU; 5-FU 2400 mg/m²; Other Names: Fluorouracil; Drug: LV; 5-FU 2400 mg/m²; Other Names: Calcium folinate; Drug: Bevacizumab; bevacizumab 5 mg/kg; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Defined as the proportion of patients who achieved complete response (CR) and partial response (PR) according to RECIST v1.1.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate	Defined as the percentage of patients who achieved CR, PR, and stable disease (SD) according to RECIST v1.1.	4 months
Duration of Response	Defined as the time from the initiation of a response (first confirmation of CR or PR) to disease progression or death from any cause, whichever occurred first.	4 months
Progress-free survival	Defined as time from the subject's enrollment to first documented disease progression using RECIST version 1.1 by investigator review or death due to any cause, whichever occurred first.	6 months
Overall survival	Defined as the time between signing the informed consent form and death due to various causes.	1 year
Incidence of adverse events	Use NCI-CTCAE version 5.0 for classification and grading	5 months

Collaborators and Investigators

• Sponsor: Hebei Medical University Fourth Hospital
• Investigators: Principal Investigator: Guiying Wang, Professor, Hebei Medical University Fourth Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: December 12, 2023
• First Submitted That Met QC Criteria: December 24, 2023
• First Posted (Actual): December 28, 2023

Study Record Updates

• Last Update Posted (Estimated): October 9, 2024
• Last Update Submitted That Met QC Criteria: October 7, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: metastatic colorectal cancer; second-line therapy; liposomal irinotecan
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Bevacizumab; Leucovorin; Irinotecan
• Other Study ID Numbers: CSPC-DEY-CRC-K04

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