Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in multimodal therapy for patients with oligometastatic peritoneal gastric cancer: a randomized multicenter phase III trial. PIPAC_VEROne
- Conditions
- Gastric adenocarcinoma with peritoneal metastases
- Registration Number
- 2024-515981-14-00
- Brief Summary
To evaluate whether the association of PIPAC with chemotherapy compared to chemotherapy alone increases the
percentage of patients who undergo surgery with radical intent (CRS and HIPEC).
To evaluate whether the association of PIPAC with chemotherapy compared to chemotherapy alone increases the
progression-free survival (PFS).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 98
Age between 18-75 years
Primary gastric adenocarcinoma of first diagnosis not previously treated
Laparoscopic finding of positive peritoneal cytology and / or peritoneal localizations of disease (PCI ≤ 6), confirmed by histological examination
Signature of informed consent
ECOG PS scale 0-1
Patients of childbearing potential will be included in the study and monitored by serum pregnancy tests before each chemotherapy cycle and each PIPAC and at the end of treatment. Oral contraceptives will not be used due to the already high thrombotic risk related to the disease, but all other contraceptives will be used according to CTFG indications on contraception.
Presence of extraperitoneal metastases
hypersensitivity to the active substances or to any of the excipients
liver failure (AST) / ALT> 3 times normal values, ALT> 3 times normal values, Bilirubin> 1.5 normal values)
Creatininemia> 1.25 mg / dL
• Ischemic / haemorrhagic stroke within the past 6 months • Acute myocardial infarction within the past 6 months • Moderate / severe heart failure (NYHA III-IV)
Leukopenia <2,000 / µl • Thrombocytopenia <100,000 / µl
Active hepatitis B or C
HIV infection
creatinine clearance less than 30ml / min
PCI> 6
Localization of the primary site of disease in the gastric esophagus junction of esophageal relevance (Siewert I-II)
Previous allergic reactions to cisplatin or doxorubicin
Haemorrhagic or occlusive manifestation of disease that candidates the patient for palliative surgery
ASA IV
Refusal of the patient to sign the consent
positive on diagnostic biopsies for EBV, MSI and HER2
pregnancy and breastfeeding
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Resectability Rate (%) evaluated as the % of patients in the 2 arms who will go to CRS and HIPEC compared to the total number of participants at the end of 6 or 12 cycles of chemotherapy in the Arm A and at the end of the 6 cycles of chemotherapy and the 3 PIPACs in arm B; PFS at 1 and 3 years measured as time from randomization at the first evidence of progression (peritoneal or extraperitoneal) or death of patient for any cause, whichever comes first. Secondary Resectability Rate (%) evaluated as the % of patients in the 2 arms who will go to CRS and HIPEC compared to the total number of participants at the end of 6 or 12 cycles of chemotherapy in the Arm A and at the end of the 6 cycles of chemotherapy and the 3 PIPACs in arm B; PFS at 1 and 3 years measured as time from randomization at the first evidence of progression (peritoneal or extraperitoneal) or death of patient for any cause, whichever comes first.
- Secondary Outcome Measures
Name Time Method overall survival at 1 and 3 years, measured as survival time from randomization until death from any cause; this endpoint will be compared between the two treatment arms overall survival at 1 and 3 years, measured as survival time from randomization until death from any cause; this endpoint will be compared between the two treatment arms
DRS at 1 and 3 years measured as survival time from randomization until cancer-related death; this endpoint will be compared between the two treatment arms DRS at 1 and 3 years measured as survival time from randomization until cancer-related death; this endpoint will be compared between the two treatment arms
For each patient in Arm B, starting from second cycle of PIPAC, a PRGS score will be assigned for each of the 4 biopsies performed, associated with an average PRGS score, given by the arithmetic mean of the individuals scores. In Arm A, this evaluation can only be carried out on the first occasion restaging after 3 months of treatment on biopsies performed during laparoscopy restaging or at the end of 6 months in those patients with stable disease who continued treatment chemotherapy For each patient in Arm B, starting from second cycle of PIPAC, a PRGS score will be assigned for each of the 4 biopsies performed, associated with an average PRGS score, given by the arithmetic mean of the individuals scores. In Arm A, this evaluation can only be carried out on the first occasion restaging after 3 months of treatment on biopsies performed during laparoscopy restaging or at the end of 6 months in those patients with stable disease who continued treatment chemotherapy
Degree of histological regression on the surgical specimen assessed using Tumor Regression Grade (TRG) sec. Mandard and compared between the two treatment arms in patients who will undergo cytoreduction and HIPEC Degree of histological regression on the surgical specimen assessed using Tumor Regression Grade (TRG) sec. Mandard and compared between the two treatment arms in patients who will undergo cytoreduction and HIPEC
The quality of life QoL assessed using the validated EORTC QLQ C30 questionnaire, administered to the patient at the beginning of recruitment and after each treatment cycle or PIPAC and compared between the two treatment arms The quality of life QoL assessed using the validated EORTC QLQ C30 questionnaire, administered to the patient at the beginning of recruitment and after each treatment cycle or PIPAC and compared between the two treatment arms
Adverse events assessed by CTCAE v.5 after each treatment cycle and after each PIPAC and compared between the two treatment arms Adverse events assessed by CTCAE v.5 after each treatment cycle and after each PIPAC and compared between the two treatment arms
Calculation of incremental cost-effectiveness ratios (Incremental Cost-Effectiveness Ratio= ICER) per additional resectable case and per year of life gained Calculation of incremental cost-effectiveness ratios (Incremental Cost-Effectiveness Ratio= ICER) per additional resectable case and per year of life gained
Trial Locations
- Locations (6)
Azienda Ospedaliera Universitaria Integrata Verona
🇮🇹Verona, Italy
Istituto Europeo Di Oncologia S.r.l.
🇮🇹Milan, Italy
Azienda Ospedaliera Universitaria Gaetano Martino Messina
🇮🇹Messina, Italy
Ospedale San Raffaele S.r.l.
🇮🇹Milan, Italy
Azienda Ospedaliera Universitaria Senese
🇮🇹Siena, Italy
Azienda Ospedaliera Di Perugia
🇮🇹Perugia, Italy
Azienda Ospedaliera Universitaria Integrata Verona🇮🇹Verona, ItalyFrancesco CasellaSite contact0458123063chirurgia.esofago.stomaco@aovr.veneto.it