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

Study Overview
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Brief Summary
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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.

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

Conditions
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Gastric Adenocarcinoma, Cancer Metastatic, Chemotherapy Effect

Intervention / Treatment
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* Drug: Pressurized intraperitoneal aerosol chemotherapy (PIPAC)
* Drug: Standard chemotherapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Arm<br> | Drug: Standard chemotherapy<br>* Patient will receive standard poly chemotherapy proposed by the oncologist or any new standard validated during the study, until progression or toxicity.<br>|
| Experimental: Experimental Arm : PIPAC<br> | Drug: Pressurized intraperitoneal aerosol chemotherapy (PIPAC)<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pressurized intraperitoneal aerosol chemotherapy (PIPAC), gastric adenocarcinoma, metastasis