Liposomal Irinotecan and Capecitabine Plus Bevacizumab as Second-line Therapy in Metastatic Colorectal Cancer

A Multicenter, Single-arm Study of Liposomal Irinotecan and Capecitabine Plus Bevacizumab as Second-line Therapy in Metastatic Colorectal Cancer

This multicenter, single-arm trial will explore the efficacy and safety of liposomal irinotecan and capecitabine plus bevacizumab as second-line therapy in metastatic colorectal cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Bevacizumab; Drug: Liposomal irinotecan; Drug: Capecitabine

Detailed Description

Colorectal cancer (CRC) has a poor prognosis and poses a serious threat to human health. irinotecan + fluorouracil ± 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+ capecitabine + bevacizumab as second-line treatment for metastatic CRC.

• Study Type: Interventional
• Enrollment (Estimated): 63
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dan Su, Ms.; Phone Number: 0451-86298278; Email: 471018565@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age: ≥18 years old.
• Histopathologically and/or cytologically confirmed unresectable metastatic colorectal adenocarcinoma, and patients failed or are intolerant to first-line treatment with oxaliplatin ± VEGF/EGFR.
• At least one measurable lesion (according to RECIST v1.1).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 ~ 1.
• 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.
• Adequate hepatic function as evidenced by: Total bilirubin ≤1.5 × upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, ≤5 × ULN if liver metastases are present. Serum albumin ≥3 g/dL.
• Adequate renal function as evidenced by serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance ≥60 mL/min. Proteinuria < 2+ (those with proteinuria ≥2+ at baseline had to demonstrate ≤1 g protein per 24 hours).
• Coagulation function: International normalised ratio (INR) ≤1.5, activated partial thromboplastin time (APTT) ≤1.5 × ULN.
• Left ventricular ejection fraction (LVEF) ≥50%.
• Subjects agree to use contraception and are not pregnant or breastfeeding women.
• 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, with the exception of cured in-situ carcinoma or basal cell carcinoma etc.
• Previous treatment with irinotecan/liposomal irinotecan.
• Patients with the primary lesion located in the left colon and RAS/BRAF wild-type who did not use cetuximab on the first line.
• Known as high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR).
• Massive pleural effusion or ascites requiring intervention.
• Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment.
• Active HIV infection.
• Combined with uncontrollable systemic diseases within 6 months before the first administration.
• Presence of severe gastrointestinal disease.
• History of major surgery (such as laparotomy, thoracotomy or intestinal resection) within 28 days before the first administration, or plan to undergo major surgery during the study period.
• Presence of interstitial pneumonia or pulmonary fibrosis.
• History of allergy or hypersensitivity to drug or any of their excipients.
• History of pulmonary hemorrhage/hemoptysis ≥Grade 2 (defined as bright red blood of at least 2.5mL) within one month before the first administration.
• Presence of arterial embolism, severe bleeding (excluding bleeding caused by surgery) or tendency for existing embolism or severe bleeding within 6 months before the first administration.
• Combined symptomatic brain metastasis, meningeal metastasis, spinal cord tumor invasion, and spinal cord compression syndrome.
• Use of strong inhibitors or inducers of CYP3A4, CYP2C8 and UGT1A1 within 14 days before the first administration.
• Use other study drug within 1 month before the first administration.
• 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: liposomal irinotecan + capecitabine + bevacizumab; liposomal irinotecan 70 mg/m², d1 + capecitabine 1000 mg/m² BID, d1~10 + bevacizumab 5mg/kg, d1. q2w	Drug: Bevacizumab; 5mg/kg IV; Other Names: Avastin; Drug: Liposomal irinotecan; 70 mg/m² IV; Other Names: nal-IRI; Drug: Capecitabine; 1000 mg/m² PO BID; Other Names: Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free Survival	Defined as the time between signing the informed consent form to the disease progression (according to RECIST v1.1 criteria) or death due to any cause.	1 year

Secondary 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.	6 months
Disease Control Rate	Defined as the proportion of patients who achieved complete response (CR), partial response (PR), and stable disease (SD) according to RECIST v1.1.	6 months
Duration of Response	Defined as the time from response(when CR or PR is first diagnosed) to disease progression or death due to any cause.	6 months
Overall survival	Defined as the time between signing the informed consent form to death due to various causes.	2 years
Incidence of adverse events	Use NCI-CTCAE version 5.0 for classification and grading.	7 months

Collaborators and Investigators

• Sponsor: Harbin Medical University
• Investigators: Principal Investigator: Yanqiao Zhang, Professor, The Second Affiliated Hospital of Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: December 21, 2023
• First Submitted That Met QC Criteria: December 21, 2023
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: second-line therapy; metastatic disease; 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; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Topoisomerase I Inhibitors; Capecitabine; Bevacizumab; Irinotecan
• Other Study ID Numbers: CSPC-DEY-CRC-K05

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