This study is a prospective, multi-cohort Phase Ib/II clinical trial, consisting of two stages as follows:
1. Phase Ib Dose-Escalation Stage To explore the dose-limiting toxicities (DLT) of intraperitoneally administered liposomal irinotecan in patients with malignant peritoneal effusion who have failed prior standard therapy, and to estimate the maximum tolerated dose (MTD) of the investigational agent. 2. Phase II Expansion Stage To evaluate the efficacy and safety of liposomal irinotecan as monotherapy or in combination with recombinant modified human tumor necrosis factor or bevacizumab, in the treatment of malignant peritoneal effusion in patients who have failed prior standard therapy.
Aged ≥18 years old, gender unrestricted.
Histologically or cytologically confirmed malignant peritoneal effusion derived from digestive system tumors (malignancy confirmed by ascites cytology, or peritoneal metastases diagnosed clinically based on imaging findings and symptoms).
Moderate to large volume of peritoneal effusion, with failure of initial treatment or previous intraperitoneal therapy with conventional chemotherapeutic agents and/or biological response modifiers. Moderate volume of ascites is defined as: ①Ascites depth ≥3 cm confirmed by supine abdominal ultrasound; ② Presence of clinical symptoms (chest distress, dyspnea, abdominal distension and discomfort) judged by the investigator to be related to peritoneal effusion.
ECOG performance status score 0-2.
History of hypersensitivity to tumor necrosis factor (TNF), its derivative drugs, bevacizumab or its analogs, irinotecan, or liposomal irinotecan.
Diagnosis of malignant diseases other than gastrointestinal tumors within 5 years prior to the first dose (excluding radically treated basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, and/or radically resected carcinoma in situ).
Receipt of any other investigational drug treatment or participation in an interventional clinical trial within 7 days prior to the first dose; or receipt of anti-tumor therapy (including Chinese herbal medicines with anti-tumor indications) within 7 days prior to the first dose of the study drug.
Pregnant or lactating women; women of childbearing potential who are unwilling to take contraceptive measures during the study period; or men who are unwilling to use effective contraceptive measures during treatment and for 1 year thereafter.
Sequential
liposomal irinotecan monotherapy
DrugA "3+3" dose-escalation design will be adopted. A total of 9-18 eligible subjects will receive liposomal irinotecan treatment, with three predefined dose levels as follows: Dose Level 1: 20 mg, intraperitoneal injection (ip), administered on Day 1, Day 8, Day 15, and Day 21. Dose Level 2: 30 mg, intraperitoneal injection (ip), administered on Day 1, Day 8, Day 15, and Day 21. Dose Level 3: 40 mg, intraperitoneal injection (ip), administered on Day 1, Day 8, Day 15, and Day 21. Each subject will receive only one treatment cycle. The dosage of liposomal irinotecan will be escalated gradually from the lowest dose level to the highest. Dose-limiting toxicities (DLT) will be monitored throughout the administration cycle. Each subject will receive only one dose level of liposomal irinotecan during the study period. All subjects will complete the relevant tests specified in the protocol during treatment to evaluate safety and preliminary efficacy. Subsequent treatment regimens will be selecte
liposomal irinotecan monotherapy
DrugLiposomal irinotecan (at RP2D, intraperitoneal injection \[ip\], administered on Day 1, Day 8, Day 15 and Day 21).
Liposomal Irinotecan + rmhTNF-NC
DrugLiposomal Irinotecan (at RP2D dose, ip, D1, D8, D15, D21) rmhTNF-NC (300 IU per administration, ip, D1, D8, D15)
Liposomal Irinotecan + Bevacizumab
DrugLiposomal Irinotecan (at RP2D dose, ip, D1, D8, D15, D21) Bevacizumab (100 mg, ip, D1, D15)
Maximum Tolerated Dose (MTD)
Defined as the highest dose at which less than 33% of subjects experience dose-limiting toxicity (DLT).
Objective Response Rate
The proportion of subjects achieving complete response and partial response per WHO criteria.
Duration of Response
The time interval from the first documentation of objective response in malignant ascites, to the first documentation of disease progression of ascites or death due to any cause, evaluated per the WHO criteria for malignant ascites.
Disease control rate
The proportion of subjects achieving complete response, partial response, or stable disease in malignant ascites, evaluated per the WHO criteria.
Safety and Tolerability
The severity of adverse events will be graded and assessed in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0,
Quality of Life
Assessment will be performed using the Chinese version of the Functional Assessment of Chronic Illness Therapy-Ascites Index (FACIT-AI) to evaluate the impact of malignant ascites and treatment on patients' physical function, symptom burden, and daily living ability.
Click on the lead sponsor to view all of their trials.
Dong sheng Zhang
Lead sponsor
Sun Yat-sen University
Sponsor institution
CSPC Pharmaceutical Group Limited
Collaborator
