Liposomal Irinotecan and 5-FU as Second-line Therapy for Patients With ESCC

Liposomal Irinotecan and 5-FU Versus Irinotecan / Irinotecan+5-fluorouracil as Second-line Therapy for Patients With Esophageal Squamous Cell Carcinoma: A Open-label, Randomized Study

The aim of this study is to compare the efficacy and safety of liposome irinotecan +5-FU and irinotecan / irinotecan +5-FU regimens in the second-line treatment of esophageal squamous cell carcinoma (ESCC).

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: liposomal irinotecan; Drug: 5-FU; Drug: LV; Drug: Irinotecan

Detailed Description

Esophageal cancer was ranked the sixth most common cancer worldwide and seventh most common cause of cancer-related deaths. ESCC is the most common histologic subtype in Asia. The National Comprehensive Cancer Network (NCCN) guidelines recommend immune checkpoint inhibitors, taxanes, fluorouracils and/or irinotecan as the second-line treatment of ESCC. 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 compare the efficacy and safety of liposome irinotecan +5-FU and irinotecan / irinotecan +5-FU regimens in the second-line treatment of esophageal squamous cell carcinoma (ESCC).

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Huiyan Luo, Professor; Phone Number: 020-87343804; Email: luohy@sysucc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age: 18-75 years old.
• Unresectable esophageal squamous cell carcinoma confirmed by histopathology and/or cytology.
• Failure or intolerance to first-line treatment.
• 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 x ULN, ≤5 x ULN if liver metastases are present. Documented serum albumin ≥ 3 g/dL.
• Adequate renal function as evidenced by serum creatinine (Cr)≤1.5 x ULN or creatinine clearance ≥60 mL/min.
• 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 prior to randomization, with the exception of cured in-situ carcinoma or basal cell carcinoma.
• Received irinotecan/irinotecan liposome based therapy in the first line.
• Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment.
• Active HIV 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)
• Allergy to or intolerance to therapeutic drugs or their excipients.
• Presence of central nervous system metastasis.
• Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1.
• Participated in other trial within 30 days or within 5 half-lives of the drug 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; liposomal irinotecan+5-FU/LV q2w	Drug: liposomal irinotecan; Liposomal irinotecan 70 mg/m²; Other Names: Nal-IRI; Drug: 5-FU; 5-FU 400 mg/m² bolus then 2400 mg/m2 over 46 h; Other Names: Fluorouracil; Drug: LV; LV 400 mg/m²; Other Names: Calcium folinate
Active Comparator: Control group; Irinotecan q2w or irinotecan+5-FU/LV q2w	Drug: 5-FU; 5-FU 400 mg/m² bolus then 2400 mg/m2 over 46 h; Other Names: Fluorouracil; Drug: LV; LV 400 mg/m²; Other Names: Calcium folinate; Drug: Irinotecan; Irinotecan 180 mg/m²; Other Names: IRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Defined as the time between the date of randomization and death due to various causes	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Use NCI-CTCAE version 5.0 for classification and grading	5 months
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
Disease Control Rate	Defined as the percentage of patients who achieved CR, PR, and stable disease (SD) according to RECIST v1.1	4 months
Progress-free survival	Defined as time from the date of randomization to first documented disease progression using RECIST version 1.1 by investigator review or death due to any cause, whichever occurred first.	5 months

Collaborators and Investigators

• Sponsor: Rui-hua Xu, MD, PhD
• Investigators: Principal Investigator: Ruihua Xu, Professor, Yat-sen University Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: July 9, 2024
• First Submitted That Met QC Criteria: July 9, 2024
• First Posted (Actual): July 15, 2024

Study Record Updates

• Last Update Posted (Actual): July 15, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: second-line therapy; esophageal squamous cell carcinoma; liposomal irinotecan
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan
• Other Study ID Numbers: CSPC-DEY-ESCC-K01

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