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).

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).

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.