FLUOROURACIL for Gastric adenocarcinoma with peritoneal metastases|Metastatic gastric adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Age between 18-75 years\n- Primary gastric adenocarcinoma of first diagnosis not previously treated\n- Laparoscopic finding of positive peritoneal cytology and / or peritoneal localizations of disease (PCI ≤ 6), confirmed by histological examination\n- Signature of informed consent\n- ECOG PS scale 0-1\n- 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."}

Exclusion criteria

• {"criterion_text":"- Presence of extraperitoneal metastases\n- PCI> 6\n- Localization of the primary site of disease in the gastric esophagus junction of esophageal relevance (Siewert I-II)\n- Previous allergic reactions to cisplatin or doxorubicin\n- Haemorrhagic or occlusive manifestation of disease that candidates the patient for palliative surgery\n- ASA IV\n- Refusal of the patient to sign the consent\n- positive on diagnostic biopsies for EBV, MSI and HER2\n- pregnancy and breastfeeding\n- hypersensitivity to the active substances or to any of the excipients\n- liver failure (AST) / ALT> 3 times normal values, ALT> 3 times normal values, Bilirubin> 1.5 normal values)\n- Creatininemia> 1.25 mg / dL\n- • Ischemic / haemorrhagic stroke within the past 6 months • Acute myocardial infarction within the past 6 months • Moderate / severe heart failure (NYHA III-IV)\n- Leukopenia <2,000 / µl • Thrombocytopenia <100,000 / µl\n- Active hepatitis B or C\n- HIV infection\n- creatinine clearance less than 30ml / min"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Secondary Resectability Rate: evaluated as the percentage of patients in each arm who undergo CRS and HIPEC compared to the total number of participants at the specified timepoints (end of 6 or 12 cycles for Arm A; end of 6 cycles and 3 PIPACs for Arm B). PFS at 1 and 3 years: measured as time from randomization to first evidence of progression (peritoneal or extraperitoneal) or death from any cause, whichever occurs first."}

Secondary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Measured as time from randomization until death from any cause; compared between treatment arms at 1 and 3 years."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Measured as time from randomization until cancer-related death; compared between treatment arms at 1 and 3 years."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"PRGS score assigned to peritoneal biopsies (4 biopsies) with an average PRGS per patient (arithmetic mean); timing differs by arm as described."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Assessed using Mandard Tumor Regression Grade on surgical specimens; compared between arms in patients undergoing cytoreduction and HIPEC."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"QoL measured by EORTC QLQ-C30 at baseline and after each cycle/PIPAC; comparisons between arms."}
• {"endpoint_text":"- Adverse events assessed by CTCAE v.5 after each treatment cycle and after each PIPAC and compared between the two treatment arms","definition_or_measurement_approach":"Safety assessed by incidence, nature and severity of adverse events graded per CTCAE v5 after each cycle and PIPAC; compared between arms."}
• {"endpoint_text":"- Calculation of incremental cost-effectiveness ratios (Incremental Cost-Effectiveness Ratio= ICER) per additional resectable case and per year of life gained","definition_or_measurement_approach":"Health economic analysis calculating ICER per additional resectable case and per year of life gained."}

Italy

Earliest CTIS Part Ii Submission Date

28-06-2024

Latest Decision Or Authorization Date

19-11-2024

Processing Time Days

144

Number Of Sites

6

Number Of Participants

98

Primary sponsor

Full Name

Azienda Ospedaliera Universitaria Integrata Verona

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy