The Safety and Efficacy of Pressurized Intraperitoneal Aerosol Chemotherapy for Peritoneal Metastatic Adenocarcinoma

Официальное название

A Prospective, Multi-center, Single-arm Clinical Research Evaluating the Safety and Efficacy of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Metastatic Adenocarcinoma

Обзор

This research is a prospective, multi-center, single-arm clinical trial aimed at assessing the standard pressurized intraperitoneal aerosol chemotherapy (PIPAC) utilizing a novel nebulized drug delivery system (NDDS) for patients with peritoneal metastatic adenocarcinoma (PMA) originating from gastric, colorectal, appendiceal, or ovarian cancer. The primary objectives of this study are to assess the safety and efficacy of PIPAC with the novel NDDS in the treatment of PMA. Primary endpoints include adverse events (AEs) and serious AEs, as assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, incidences of device defects, postoperative pain scores evaluated using the Visual Analogue Scale / Score (VAS), and quality of life as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 scale, Version 3.0). Secondary endpoints include the intra-abdominal peritoneal cancer index (PCI), peritoneal regression grading score (PRGS), objective response rate (including partial response (PR) and complete response (CR)), improvement in ascites, conversion rate (patients proceeding to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) following initial PIPAC treatments), progression-free survival (PFS), and overall survival (OS).

Подробное описание

Peritoneal metastasis (PM) is acknowledged as the final stage of various abdominal cancers and correlates with dismal prognosis, with survival generally under six months when exclusively managed with systemic chemotherapy due to the plasma-peritoneal barrier. Recent clinical evidence, primarily from Western nations, has shown that pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a viable, safe, and effective method for PM. Nonetheless, clinical data regarding the utilization of PIPAC in Asian populations, especially among Chinese patients, are still scarce. This study seeks to evaluate the safety and efficacy of PIPAC employing a novel nebulized drug delivery system (NDDS) for the treatment of peritoneal metastatic adenocarcinoma (PMA).

The NDDS novel consists of a central computer with an operating system, a high-pressure peristaltic pump, an emergency stops switch, a liquid level sensor, and an integrated unit featuring a 10-mm spray nozzle, an anti-high-pressure infusion tube, and a puncture head. PIPAC is conducted under a standard 12 mmHg pneumoperitoneum. Doxorubicin and cisplatin are administered for patients with PMA originating from gastric or ovarian cancers, whereas oxaliplatin is utilized for PMA resulting from colorectal or appendiceal cancers. Customized treatment protocols, encompassing drug dosages, are established by a multidisciplinary peritoneal carcinomatosis committee before the administration of PIPAC.

Qualified patients will undergo three cycles of PIPAC in conjunction with concurrent systemic chemotherapy (e.g., XELOX or FOLFOX). The interval between successive PIPAC procedures is 4 to 6 weeks, with an additional interval of one to two weeks between PIPAC and systemic chemotherapy. The anticipated therapy duration for each patient is three months, during which the primary and secondary endpoints will be assessed.

This research will take place in 25 domestic medical centers, aiming for a sample size of 30 cases.

Вмешательства

• Препарат Pressurized Intraperitoneal Aerosol Chemotherapy
  The comprehensive therapeutic strategy will be modified based on the integrated 2- or 3-week systemic chemotherapies. In the interim, a total of three PIPAC procedures will be conducted for all qualifying patients. 1. PIPAC combined with 2-week systemic chemotherapies: PIPAC therapy will occur every four weeks, while systemic chemotherapies will be administered during the first and third weeks following the initial and second PIPAC procedures respectively. 2. PIPAC combined with 3-week syst

Первичные конечные точки

• Adverse Events (AE) and serious AE associated with Treatment [Срок оценки: 4-6 weeks following the initial and secondary PIPAC procedures, and 6 months subsequent to the tertiary PIPAC procedure]
• Incidences of device defects [Срок оценки: During each PIPAC therapy]
• Postoperative pain scores [Срок оценки: The first to seventh day after the PIPAC procedure]
• Quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Version 3.0) [Срок оценки: 4-6 weeks following the initial and second PIPAC procedures, and 6 months subsequent to the third PIPAC procedure]

Вторичные конечные точки (7)

• Intra-abdominal peritoneal cancer index (PCI) [Срок оценки: During each PIPAC procedure]
• Peritoneal regression grading score (PRGS) [Срок оценки: During each PIPAC procedure]
• Objective response rate (partial and complete response) [Срок оценки: Within 6 months after the third PIPAC procedure]
• Improvement in ascites [Срок оценки: During each PIPAC procedure]
• Conversion rate [Срок оценки: 4-6 weeks following the initial and secondary PIPAC procedures, and 6 months after the tertiary PIPAC procedure]
• Progression-free survival (PFS) [Срок оценки: 6 months after the second or third PIPAC procedure]
• Overall survival (OS) [Срок оценки: 6 months after the second or third PIPAC procedure]

Критерии участия

Критерии включения

• Histopathology verified that peritoneal metastatic adenocarcinoma (PMA) arises from gastric, colorectal, appendiceal, or ovarian carcinoma;
• Applicable to individuals of either sex, aged between 18 and 75 years;
• Eastern Cooperative Oncology Group (ECOG) scale ≤ 2;
• Absence of other concurrent malignancies;
• Without contraindications for laparoscopic surgery;
• Laboratory testing: blood routine examination: neutrophil count ≥ 1.5× 10\^9/L, platelet count ≥ 80 × 10\^9/L, hemoglobin ≥ 80g/L ; blood biochemistry: serum total bilirubin ≤ 1.5 ×ULN, Alanine transaminase and aspartate aminotransferase ≤ 2.5 ×ULN, serum creatinine ≤ 1.5 ×ULN;
• Life expectancy > 6 months;
• Informed consent understood and signed.

Критерии исключения

• Presenting symptoms of gastrointestinal obstruction;
• Fully reliant on parenteral nutrition;
• Exhibiting decompensated ascites;
• Suffering from severe abdominal infection (indications of peritonitis);
• Characterized by extensive adhesions in the abdominal cavity;
• Concurrently undergoing cytoreductive surgery (CRS) or gastrointestinal tract resection and reconstruction procedures;
• With portal vein thrombosis;
• Concurrently, individuals with significant or unmanaged medical conditions or infections (including atrial fibrillation, angina, cardiac dysfunction, ejection fraction < 50%, refractory hypertension etc.);
• Previous chemotherapeutic drugs allergy;
• Severe cardiopulmonary, hepatonephric, hematologic, and metal diseases, or drug abuse;
• Pregnancy or lactating women;
• Engage in additional clinical trials within three months preceding recruitment;
• Other conditions: patients are inappropriately included as determined by researchers.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Guangdong Provincial People's Hospital — Гуанчжоу

Идентификаторы

NCT: NCT06743867 · PIPAC-HOPE-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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