Oxaliplatin for Colorectal cancer|Peritoneal metastases

Inclusion criteria

• {"criterion_text":"- 1)\tAge ≥ 18 years;\n- 2)\tWritten informed consent obtained from the patient before any study procedure;\n- 3)\tECOG performance status of 0 to 2;\n- 4)\tHistopathologically confirmed colonic adenocarcinoma with synchronous or metachronous peritoneal metastasis (PM);\n- 5)\tUnresectable PM defined as any of the following: -\tPCI >15 -\tExtended small bowell involvement -\tPoor general condition contra-indication to a major abdominal surgery (eg: a complete cytoreductive surgery ), as decided by the medico-surgical team of the investigator’s site specialised in peritoneal carcinomatosis in charge of the patient.\n- 6)\tA surgical exploration performed less than 4 weeks before inclusion (if not, a laparoscopic exploration must be performed);\n- 7)\tIndication of first line systemic chemotherapy for advanced / metastatic colonic adenocarcinoma. Systemic chemotherapy in an adjuvant setting is allowed if completed more than 6 months before recurrence and without persistent oxaliplatin-induced neuropathy;\n- 8)\tNo extended intraperitoneal adherences confirmed by surgical exploration (laparoscopy or laparotomy) in at least 9 out of 13 abdominal regions;\n- 9)\tNeutrophils count ≥ 1.5 x 109/L, platelet count ≥ 100 x109/L, hemoglobin ≥ 9 g/dL; Total bilirubin < 1.5 x ULN (upper limit of normal), ASAT and ALAT <3 x ULN, Alkaline phosphatase <1.5 x ULN, Serum creatinine < 1.5 x ULN;\n- 10)\tCreatinine clearance ≥ 30 mL/min\n- 11)\tMen and women* must use effective contraceptive measures during the treatment and for at least 15 months after the last dose received; (* of childbearing age);\n- 12)\tNo known risk of irinotecan toxicity\n- 13)\tNo Dihydropyrimidine dehydrogenase deficit (uracil blood Level <16ng/ml);\n- 14)\tPatient is willing and able to comply with the protocol for the duration of the study, including treatment and scheduled visits and examinations, including follow up;\n- 15)\tPatient has valid health insurance."}

Exclusion criteria

• {"criterion_text":"- 1)\tOther cancer treated within the last 3 years, with the exception of in situ cervical carcinoma or basocellular carcinoma;\n- 2)\tRectal cancer primary (tumor <15 cm from the anal verge);\n- 3) Mutational status corresponding to microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR)\n- 4)\tComplete or partial bowel obstruction unresponsive to medical treatment;\n- 5)\tExtraperitoneal polymetastatic diseases. (Only oligometastatic1 diseases are allowed for inclusion) 1. 1oligo-metastatic disease as defined up to 3 liver metastases less than 5 cm in diameter and/or up to 3 lung nodules less than 10 mm in diameter and/or ovarian metastasis of any size.\n- 6)\tHistory of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within 6 months prior to enrolment;\n- 7)\tActive gastrointestinal bleeding;\n- 8)\tSevere ongoing infection;\n- 9)\tClinically relevant and uncontrolled coronary heart disease, myocardial infarction within the past 12 months;\n- 10)\tUncontrolled arrhythmia;\n- 11)\tUncontrolled hypertension;\n- 12)\tInflammatory bowel disease;\n- 13)\tOngoing non-healing wounds, ulcers or bone fractures;\n- 14)\tRelevant proteinuria (nephrotic syndrome); arterial thromboembolisms or severe haemorrhages within 6 months before study enrolment (except a bleeding tumour before tumour resection surgery) precluding the use of anti-VEGF drug;\n- 15)\tHaemorrhagic diathesis or thrombotic tendency;\n- 16)\tPeripheral neuropathy oxaliplatin-related according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0;\n- 17)\tNo reversible electrolyte disorders such as hypokalemia, hypocalcemia or hypomagnesemia.\n- 18)\tQT/QTc interval longer than 450 msec for men and longer than 470 msec for women on the inclusion ECG\n- 19)\tKnown history of hypersensibility to fluorouracil, folinic acid, irinotecan, oxaliplatin, capecitabine, cetuximab, panitumumab, bevacizumab or to any of their excipients, according to the SmPCs of these products.\n- 20)\tConcomitant treatment with brivudine, sorivudine or their chemically related analogues (according to the SmPC of fluorouracile)\n- 21)\tLive attenuated vaccines and for 6 months following cessation of chemotherapy (according to the SmPCs of fluorouracile and irinotecan);\n- 22)\tConcomitant use with St John's Wort (according to the SmPC of irinotecan);\n- 23)\tSevere renal insufficiency (creatinine clearance < 30 mL/min, according to the SmPC of capecitabine;\n- 24)\tHistory of allergy to red meat or tick bites or positive results of tests for IgE antibodies against cetuximab (α-1-3-galactose) (according to the SmPC of cetuximab);\n- 25)\tInterstitial lung disease (according to the SmPCs of cetuximab and panitumumab);\n- 26)\tPulmonary fibrosis (according to the SmPC of panitumumab);\n- 27)\tHypersensitivity to Chinese hamster ovary (CHO) cell products (according to the SmPC of bevacizumab)\n- 28)\tPregnancy or breast-feeding period;\n- 29)\tMedical, geographical, sociological, psychological or legal conditions that would not permit the patient completing the study or signing the informed consent form.\n- 30)\tAppendix cancer"}

Primary endpoints

• {"endpoint_text":"- Progression free survival (PFS) is defined as the time (in months) from randomisation until the date of progression or death from any cause.","definition_or_measurement_approach":"Defined as the time (in months) from randomisation until the date of progression or death from any cause."}

Secondary endpoints

• {"endpoint_text":"- a) Overall survival (OS) defined as the time relapsed between randomisation and death from any cause","definition_or_measurement_approach":"Defined as the time between randomisation and death from any cause."}
• {"endpoint_text":"- b) EORTC QLQ-C30 (Appendix 12) and the EORTC QLQ-CR29 (Appendix 13) questionnaires","definition_or_measurement_approach":"Quality of life measured using EORTC QLQ-C30 and EORTC QLQ-CR29 questionnaires."}
• {"endpoint_text":"- c) •\tToxicities ≥ grade 3 related to chemotherapy (IV, PO or PIPAC), targeted therapy and abdominal surgery (laparoscopy, PIPAC procedure, biopsies, CRS) assessed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (Appendix 10); •\tToxicities ≥ grade 3 related to abdominal surgery as assessed by the CLAVIEN DINDO score (Appendix 11). •\tToxicities of any grade about peripheral neuropathy assessed according to the Common Terminology Criteria for Adverse Events (CTC","definition_or_measurement_approach":"Toxicities assessed according to CTCAE v5.0; surgical toxicities also assessed by CLAVIEN DINDO; peripheral neuropathy by CTCAE."}
• {"endpoint_text":"- d) Resection rate defined as proportion of patients who proceed to secondary cytoreductive surgery CC0 or CC1 with or without hyperthermic intraperitoneal chemotherapy (HIPEC)","definition_or_measurement_approach":"Proportion of patients undergoing secondary cytoreductive surgery CC0 or CC1 (with or without HIPEC)."}
• {"endpoint_text":"- e) Peritoneal progression free survival defined as the time between the date of randomisation and the date of peritoneal progression or death from any cause.","definition_or_measurement_approach":"Time from randomisation to peritoneal progression or death from any cause."}
• {"endpoint_text":"- f) OFS is defined as the time between the date of randomisation and the appearance of gastrointestinal obstruction requiring medication with high dose of corticosteroïd (> 1mg/kg) or intervention as nasogastric decompression, intraluminal stenting, surgical bypass, or decompression stomy (gastrostomy or ileo/colostomy) or death.","definition_or_measurement_approach":"Time from randomisation to gastrointestinal obstruction requiring specified interventions or death."}
• {"endpoint_text":"- g) Peritoneal regression grading score (PRGS) (Appendix 6) on biopsies performed at surgical exploration in both groups, and systematically during 1st and 2nd PIPAC procedure.","definition_or_measurement_approach":"PRGS assessed on biopsies at surgical exploration and during 1st and 2nd PIPAC."}
• {"endpoint_text":"- h) PCI < 20 and PCI ≥ 20","definition_or_measurement_approach":"Analysis of PFS by baseline PCI categories (<20 vs ≥20)."}
• {"endpoint_text":"- i) PFS benefit of adding PIPAC to systemic chemotherapy after baseline PCI: PCI < 20 and PCI ≥ 20","definition_or_measurement_approach":"Evaluation of PFS benefit of PIPAC stratified by baseline PCI (<20 vs ≥20)."}
• {"endpoint_text":"- j) PFS according to PRGS (1-2 vs 3-4) after the 2nd PIPAC","definition_or_measurement_approach":"Comparison of PFS according to PRGS categories (1-2 vs 3-4) after 2nd PIPAC."}
• {"endpoint_text":"- k) PFS following tumor mutation status (KRAS wt vs KRAS mt and BRAF wt vs BRAF mt)","definition_or_measurement_approach":"Analysis of PFS by tumor mutation status (KRAS and BRAF wild-type vs mutated)."}

France

Earliest CTIS Part Ii Submission Date

26-08-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

564

Number Of Sites

16

Number Of Participants

114

Primary sponsor

Full Name

Institut De Cancerologie De L Ouest

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France