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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06192680
• Other study ID #: CSPC-DEY-CRC-K05
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 1, 2024
• Est. completion date: September 30, 2026

Study information

• Verified date: January 2024
• Source: Harbin Medical University
• Contact: Dan Su, Ms.
• Phone: 0451-86298278
• Email: 471018565[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 63
• Est. completion date: September 30, 2026
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• Liposomal irinotecan
70 mg/m² IV
• Capecitabine
1000 mg/m² PO BID
• Bevacizumab
5mg/kg IV

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Harbin Medical University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Overall survival	Defined as the time between signing the informed consent form to death due to various causes.	2 years
Secondary	Incidence of adverse events	Use NCI-CTCAE version 5.0 for classification and grading.	7 months