Clinical trial NCT06743867: The Safety and Efficacy of Pressurized Intraperitoneal Aerosol Chemotherapy for Peritoneal Metastatic Adenocarcinoma
Official title: A Prospective, Multi-center, Single-arm Clinical Research Evaluating the Safety and Efficacy of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Metastatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Peritoneal Carcinoma Metastatic
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
Collaborators: name: Tianjin Third Central Hospital
name: Peking University Cancer Hospital & Institute
name: Second Affiliated Hospital of Guangzhou Medical University
name: The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine
name: Henan Cancer Hospital
name: Tongji Hospital
name: Wuhan Union Hospital, China
name: Jiangxi Provincial Cancer Hospital
name: The First Affiliated Hospital of Air Force Medicial University
name: Nanfang Hospital, Southern Medical University
name: Southern Medical University, China
name: Affiliated Hospital of Qinghai University
name: Ruijin Hospital
name: Shenzhen Second People's Hospital
name: West China Hospital
name: Tianjin Nankai Hospital
name: Wannan Medical College Yijishan Hospital
name: Second Affiliated Hospital of Wenzhou Medical University
name: Changzhi People's Hospital
name: First Hospital of China Medical University
name: Xiangya Hospital of Central South University
name: Sixth Affiliated Hospital, Sun Yat-sen University
name: Sun Yat-sen University
name: Fujian Medical University Union Hospital
First posted: 2024-12-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Histopathology verified that peritoneal metastatic adenocarcinoma (PMA) arises from gastric, colorectal, appendiceal, or ovarian carcinoma;
2. Applicable to individuals of either sex, aged between 18 and 75 years;
3. Eastern Cooperative Oncology Group (ECOG) scale ≤ 2;
4. Absence of other concurrent malignancies;
5. Without contraindications for laparoscopic surgery;
6. 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;
7. Life expectancy \> 6 months;
8. Informed consent understood and signed.

Exclusion Criteria:

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

Primary outcomes:
measure: Adverse Events (AE) and serious AE associated with Treatment
timeFrame: 4-6 weeks following the initial and secondary PIPAC procedures, and 6 months subsequent to the tertiary PIPAC procedure
measure: Incidences of device defects
timeFrame: During each PIPAC therapy
measure: Postoperative pain scores
timeFrame: The first to seventh day after the PIPAC procedure
measure: Quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Version 3.0)
timeFrame: 4-6 weeks following the initial and second PIPAC procedures, and 6 months subsequent to the third PIPAC procedure
Secondary outcomes:
measure: Intra-abdominal peritoneal cancer index (PCI)
timeFrame: During each PIPAC procedure
measure: Peritoneal regression grading score (PRGS)
timeFrame: During each PIPAC procedure
measure: Objective response rate (partial and complete response)
timeFrame: Within 6 months after the third PIPAC procedure
measure: Improvement in ascites
timeFrame: During each PIPAC procedure
measure: Conversion rate
timeFrame: 4-6 weeks following the initial and secondary PIPAC procedures, and 6 months after the tertiary PIPAC procedure
measure: Progression-free survival (PFS)
timeFrame: 6 months after the second or third PIPAC procedure
measure: Overall survival (OS)
timeFrame: 6 months after the second or third PIPAC procedure
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
Study officials:
References: