Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Gastric Carcinomatosis. Phase II Randomized Study (PIPAC EstoK 01)

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Gastric Carcinomatosis. Phase II Randomized Study - PIPAC EstoK 01

Peritoneal metastasis is a common pattern in advanced gastric cancer leading to a terminal condition in a very short time. Whatever recent progress regarding systemic chemotherapy using multi drugs association median survival is limited to 6 months with altered quality of life (QoL) after 4 months for all patients. We postulated that a new innovative health technology for delivering intraperitoneal pressurized aerosol of chemotherapy (Doxorubicin and Cisplatin) during laparoscopy can transform that situation offering to double the survival with QoL preservation. Interestingly, PIPAC procedure is made to be applied repeatedly, every 4 to 6 weeks. This therapeutic strategy allows to improved Intra Peritoneal (IP) drugs impregnation and maintained Intra-Veinous (IV) chemotherapy meanwhile. The primary objective of this study is to evaluate and compare 24-month progression free-survival in patients with peritoneal carcinomatosis of gastric cancer treated either with IV chemotherapy and Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) or with IV chemotherapy alone, with preservation of quality of life.

Study Overview

• Status: Completed
• Conditions: Gastric Adenocarcinoma; Chemotherapy Effect; Cancer Metastatic
• Intervention / Treatment: Drug: Standard chemotherapy; Drug: Pressurized intraperitoneal aerosol chemotherapy (PIPAC)

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lille, France, 59000
    • Hôpital Universitaire Claude Huriez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 < age ≤ 75 years
• Performance status (WHO) < 2
• White blood cells > 3.500 /mm3; neutrophils > 1.500 /mm3; platelets > 100.000 /mm3
• Creatinemia < 1.5 x Normal, Normal ASAT, ALAT and Serum total bilirubin, Normal ionic balance (potassium, calcium, magnesium and phosphorus
• An acceptable nutritional condition with Body Mass Index (BMI) > 18.5 kg/m2, Albumin > 30 g/l, pre-albumin > 110 mg/l
• Effective contraception for patients of childbearing age
• Written consent obtained prior any act of the research
• Patient with social insurance
• Patient having synchronous or metachronous peritoneal metastasis or ovarian metastasis of a gastric adenocarcinoma cancer, including adenocarcinoma with independent cells (ADCI) or linitis
• Patients with or without primary gastric tumor could be included
• Peritoneal Cancer Index (PCI) > 8

Exclusion Criteria:

• Weight loss > 20% of total body weight before disease
• Presence of uncontrolled comorbidities including severe chronic disease or organ insufficiency
• Contraindication to any drug contained in the chemotherapy regimen, according to summary of product characteristic's
• Having any form of previous intra-abdominal chemotherapy or intra-abdominal antibody therapy
• Patients with history of allergic reactions to platinum compounds or doxorubicin
• Complete deficiency of the enzyme dihydropyrimidine dehydrogenase.
• Patients are not allowed to undergo any cancer-specific treatment during the trial.
• Secondary debulking surgery is not allowed during PIPAC treatment
• Pregnancy or breastfeeding
• Patient under guardianship
• Other systemic metastases (liver, lung, bone, brain) or lombo-aortic lymph node involvement
• Pleural effusion requiring evacuation for respiratory failure
• Small bowel occlusion with no possible food intake
• Ascites > 3 liters
• HER2 +++ tumor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Arm	Drug: Standard chemotherapy; Patient will receive standard poly chemotherapy proposed by the oncologist or any new standard validated during the study, until progression or toxicity.
Experimental: Experimental Arm : PIPAC	Drug: Pressurized intraperitoneal aerosol chemotherapy (PIPAC); After insufflation of a 12 mmHg of capnoperitoneum at 37°C, two balloons safety trocars (10 and 12mm) are inserted into the abdominal wall. Injection of Doxorubicin (2.1 mg/m2 in 50 ml NaCl 0.9%) and Cisplatin (10.5 mg/m2 body surface in 150 ml NaCl 0.9%) with a flow rate of 0.7ml/s, the therapeutic capnoperitoneum is maintained for 30 min at body temperature.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free survival	24-month progression free-survival, defined as time from randomization to any clinical (ascites, abdominal pain, weight loss > 10% of total body weight) and/or morphological signs (systemic metastases, ascites, progression with RECIST criteria) of recurrence (local or systemic) or death.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain H6	Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain)	6 hours after end of surgery
Postoperative pain H12	Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain)	12 hours after end of surgery
Postoperative pain H18	Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain)	18 hours after end of surgery
Postoperative pain H24	Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain)	24 hours after end of surgery
Postoperative pain H30	Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain)	30 hours after end of surgery
Postoperative pain H36	Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain)	36 hours after end of surgery
Postoperative pain H42	Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain)	42 hours after end of surgery
Postoperative pain H48	Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain)	48 hours after end of surgery
Overall survival	Progression Free survival	24 months
Secondary resectability rate	Secondary resectability rate after the treatment	24 months
Quality of life	Quality of life evaluated monthly by the patient with the EORTC QLQ-STO22 questionnaire	monthly until death or 24 months
Quality of health status	Quality of health status evaluated monthly by the patient with the EQ-5D-5L questionnaire	monthly until death or 24 months
Toxicity	Rate of treatment-related toxicity at 60 days of each PIPAC procedure	60 days
PIPAC success	Rate of successful PIPAC procedures	24 hours
Morbidity Clavien-Dindo	Morbidity will be evaluated on post-operative day 60 by the Clavien-Dindo classification (I to V)	60 days
Morbidity Complication Index	Morbidity will be evaluated by the Comprehensive Complication Index, ranging from 0 to 100 (https://www.assessurgery.com/about_cci-calculator)	60 days
Discontinuation	The time of discontinuation defined as the time from randomization to therapy change or dose reduction because of progression of disease or intolerance or adverse effects or patient refusal or death.	24 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2020
• Primary Completion (Actual): March 2, 2024
• Study Completion (Actual): March 2, 2024

Study Registration Dates

• First Submitted: August 21, 2019
• First Submitted That Met QC Criteria: August 21, 2019
• First Posted (Actual): August 22, 2019

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 13, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: gastric adenocarcinoma; pressurized intraperitoneal aerosol chemotherapy (PIPAC); metastasis
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma
• Other Study ID Numbers: P160951J; 2018-004755-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No