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

Colorectal Cancer Clinical Trial

Official title:

A Multi-center, Single-arm Study of Liposomal Irinotecan and Leucovorin/5-fluorouracil Plus Bevacizumab as Second-line Therapy in Metastatic Colorectal Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06184698
• Other study ID #: CSPC-DEY-CRC-K04
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 1, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: November 2023
• Source: Hebei Medical University Fourth Hospital
• Contact: Xuhua Hu, Doctor
• Phone: 0311-86095347
• Email: huxvhua[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age: =18 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.

• 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, such as unstable angina, myocardial infarction, congestive heart failure, severe unstable ventricular arrhythmia, severe pericardial disease history and other cardiovascular diseases; uncontrolled hypertension(Defined as systolic blood pressure=140 mmHg and/or diastolic blood pressure=90 mmHg after treatment with standardized antihypertensive drugs), or history of critical hypertension, hypertensive encephalopathy; uncontrollable diabetes, etc.

• 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.

• Presence of central nervous system metastasis.

• 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 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
liposomal irinotecan 70 mg/m²
• 5-FU
5-FU 2400 mg/m²
• LV
5-FU 2400 mg/m²
• Bevacizumab
bevacizumab 5 mg/kg

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hebei Medical University Fourth Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Disease Control Rate	Defined as the percentage of patients who achieved CR, PR, and stable disease (SD) according to RECIST v1.1.	4 months
Secondary	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
Secondary	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
Secondary	Overall survival	Defined as the time between signing the informed consent form and death due to various causes.	1 year
Secondary	Incidence of adverse events	Use NCI-CTCAE version 5.0 for classification and grading	5 months