Clinical trial NCT06784765: Preventive Use of PIPAC in Locally Advanced Gastric Cancer.
Official title: Preventive Use of Pressurized Intraperitoneal Aerosol Chemotherapy in Locally Advanced Gastric Cancer: A Non-Randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Gastric Cancer
Keywords: Gastric Cancer
peritoneal carcinomatosis
gastrectomy
PIPAC
FLOT
Lead sponsor: National Research Oncology and Transplantology Center, Kazakhstan
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Higher Education of the Republic of Kazakhstan
First posted: 2025-01-20
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Gastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related mortality. In patients with locally advanced gastric cancer, multimodal treatment strategies, including perioperative chemotherapy, have significantly improved survival rates. Despite these advances, peritoneal carcinomatosis (PC) remains a serious problem, occurring in 60% of cases after radical surgery. PC is associated with poor prognosis and limited treatment options.

Intra-abdominal chemotherapy, particularly hyperthermic intraperitoneal chemoperfusion (HIPEC), has demonstrated advantages in the treatment of PC. However, a new technique, pressurized intraperitoneal aerosolized chemotherapy (PIPAC), is emerging as a promising alternative. PIPAC delivers chemotherapeutic agents directly to the peritoneal surface as an aerosol, allowing deeper penetration of drugs into tumor implants while minimizing toxicity and invasiveness.

This study hypothesizes that the addition of PIPAC as a preoperative treatment for patients with locally advanced gastric cancer may reduce the incidence of peritoneal carcinomatosis compared to standard therapy. The primary objective of this study is to determine whether preoperative PIPAC reduces the incidence of peritoneal carcinomatosis in these patients.

Detailed description: Gastric cancer is the fifth most common cancer globally and the third leading cause of cancer-related death. In patients with locally advanced gastric cancer, multimodal treatment strategies, including perioperative chemotherapy, have significantly improved survival outcomes. However, PC remains a major challenge, often occurring in 60% of cases after radical surgery, and is associated with a poor prognosis and limited treatment options.

Intra-abdominal chemotherapy, particularly HIPEC, has shown benefits in the treatment of PC. However, a newer method, PIPAC, is emerging as a promising alternative. PIPAC delivers chemotherapeutic agents directly to the peritoneal surface via aerosol, ensuring deeper penetration of the drugs into tumor implants and offering lower toxicity and less invasiveness compared to traditional methods.

This study hypothesizes that adding PIPAC as a preoperative treatment in patients with locally advanced gastric cancer may reduce the occurrence of peritoneal carcinomatosis compared to standard therapy alone. PIPAC will be applied before neoadjuvant chemotherapy to patients at high risk for peritoneal recurrence, with the goal of improving survival rates and reducing recurrence after surgery.

The main objectives of this study are to determine whether preoperative PIPAC reduces the incidence of peritoneal carcinomatosis in patients with locally advanced gastric cancer. Secondary objectives include assessing overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), the occurrence of serious adverse events (SAEs), quality of life (QoL) as measured by the EORTC QLQ-C30, postoperative mortality (Clavien-Dindo classification), and pathological response (TRG) in comparison to patients receiving standard treatment.

Eligibility criteria: Adults aged 18-70 years with histologically confirmed locally advanced gastric adenocarcinoma (T3-4N0-3M0), ECOG performance status 0-2, and negative peritoneal cytology.

Inclusion Criteria:

1. Signed informed consent
2. Aged 18-70 years
3. ECOG performance status 0-2
4. Histologically confirmed adenocarcinoma of the stomach (T3-4N0-3M0)
5. Negative peritoneal cytology from diagnostic laparoscopy
6. No prior chemotherapy or radiotherapy

Exclusion Criteria:

1. Presence of distant metastases
2. Positive peritoneal cytology
3. Previous cancer treatment (chemotherapy, radiotherapy, or surgery)
4. Severe comorbid conditions contraindicating surgery or chemotherapy
5. Pregnancy or lactation
6. Known hypersensitivity to study drugs

Primary outcomes:
measure: Incidence of peritoneal carcinomatosis
timeFrame: 12, 24 months after surgery
Secondary outcomes:
measure: Overall survival
timeFrame: 1. 3, 5 years after surgery
measure: Disease-free survival
timeFrame: 3, 6, 9, 12, 18, 24 months after surgery
measure: Quality of life by EORTC QLQ-C30
timeFrame: before surgery, 3 months after surgery, 6 months after surgery, 12 months after surgery
measure: Frequency of adverse events
timeFrame: through study completion, 30 days after surgery, 90 days after surgery
Other outcomes:
Locations:
city: Astana
country: Kazakhstan
facility: National Research Oncology Centre
Study officials:
References:
citation: Sgarbura O, Eveno C, Alyami M, Bakrin N, Guiral DC, Ceelen W, Delgadillo X, Dellinger T, Di Giorgio A, Kefleyesus A, Khomiakov V, Mortensen MB, Murphy J, Pocard M, Reymond M, Robella M, Rovers KP, So J, Somashekhar SP, Tempfer C, Van der Speeten K, Villeneuve L, Yong WP, Hubner M. Consensus statement for treatment protocols in pressurized intraperitoneal aerosol chemotherapy (PIPAC). Pleura Peritoneum. 2022 Mar 1;7(1):1-7. doi: 10.1515/pp-2022-0102. eCollection 2022 Mar 1.
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citation: Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. doi: 10.1056/NEJMoa010187.
citation: Cotte E, Passot G, Gilly FN, Glehen O. Selection of patients and staging of peritoneal surface malignancies. World J Gastrointest Oncol. 2010 Jan 15;2(1):31-5. doi: 10.4251/wjgo.v2.i1.31.