Cancer Metastatic, Chemotherapy Effect, Gastric Adenocarcinoma
Conditions
Keywords
pressurized intraperitoneal aerosol chemotherapy (PIPAC), gastric adenocarcinoma, metastasis
Brief summary
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.
Interventions
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.
DRUGStandard chemotherapy
Patient will receive standard poly chemotherapy proposed by the oncologist or any new standard validated during the study, until progression or toxicity.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free survival | 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative pain H12 | 12 hours after end of surgery | Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain) |
| Postoperative pain H18 | 18 hours after end of surgery | Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain) |
| Postoperative pain H24 | 24 hours after end of surgery | Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain) |
| Postoperative pain H30 | 30 hours after end of surgery | Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain) |
| Postoperative pain H36 | 36 hours after end of surgery | Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain) |
| Postoperative pain H42 | 42 hours after end of surgery | Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain) |
| Postoperative pain H48 | 48 hours after end of surgery | Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain) |
| Overall survival | 24 months | Progression Free survival |
| Postoperative pain H6 | 6 hours after end of surgery | Postoperative pain with a numeric rating scale from 0 to 10 (0 being no pain and 10 the worst possible pain) |
| Quality of life | monthly until death or 24 months | Quality of life evaluated monthly by the patient with the EORTC QLQ-STO22 questionnaire |
| Quality of health status | monthly until death or 24 months | Quality of health status evaluated monthly by the patient with the EQ-5D-5L questionnaire |
| Toxicity | 60 days | Rate of treatment-related toxicity at 60 days of each PIPAC procedure |
| PIPAC success | 24 hours | Rate of successful PIPAC procedures |
| Morbidity Clavien-Dindo | 60 days | Morbidity will be evaluated on post-operative day 60 by the Clavien-Dindo classification (I to V) |
| Morbidity Complication Index | 60 days | Morbidity will be evaluated by the Comprehensive Complication Index, ranging from 0 to 100 (https://www.assessurgery.com/about\_cci-calculator) |
| Discontinuation | 24 months | 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. |
| Secondary resectability rate | 24 months | Secondary resectability rate after the treatment |
Countries
France
Outcome results
None listed