OXALIPLATIN for Metastatic colorectal cancer (RAS and BRAF wild-type)

Inclusion criteria

• {"criterion_text":"- Age between 18 and 75 years\n- Patient affiliated to a social security regimen\n- Patient information and signed written consent form\n- Uracilemia < 16 ng/ml\n- ECOG PS between 0 and 1\n- Histologically confirmed adenocarcinoma of the colon or rectum\n- Untreated synchronous or metachronous metastatic disease deemed unresectable with curative intent\n- K-Ras (codons 12, 13, 59, 61, 117, 146), N-Ras (codons 12, 13, 59, 61) and B-Raf (codon 600) wild-type tumor status according to plasma analysis of circulating cell free DNA by Intplex technology\n- Measurable disease according to RECIST version 1.1\n- Adequate hematologic, hepatic and renal functions:  Absolute neutrophil count (ANC) ≥2 x 109/L  Haemoglobin ≥9 g/dL  Platelets (PTL) ≥100 x 109/L  AST/ALT ≤5 x ULN  Alkaline phosphatase ≤2.5 x ULN  Bilirubin ≤1.5 x ULN  Creatinine clearance ≥50 mL/min (Cockcroft and Gault formula)\n- Life expectancy of at least 3 months\n- Adequate contraception if applicable"}

Exclusion criteria

• {"criterion_text":"- History of other malignancy within the previous 5 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma)\n- Adjuvant treatment with oxaliplatin\n- Previous treatment for metastatic disease\n- Patients who received any chemo- and/or radiotherapy within 15 days from the date of blood sampling for the RAS and BRAF test\n- Brain metastases\n- Patients with a history of severe or life-threatening hypersensitivity to the active substances or to any of the excipients delivered in this study\n- Patient with history of pulmonary fibrosis or interstitial pneumonitis\n- Previous organ transplantation, HIV or other immunodeficiency syndromes\n- Concomitant medications/comorbidities that may prevent the patient from receiving study treatment as uncontrolled intercurrent illness (for instance: active infection, active inflammatory disorders, inflammatory bowel disease, intestinal obstruction, symptomatic congestive heart failure, uncontrolled hypertension…)\n- Persistent peripheral neuropathy >grade1 (NCI CT v4.03)\n- Ionic disorders as:  Kalemia ≤1 x LLN  Magnesemia <0.5mmol/L  Calcemia <2mmol/L\n- Patient with known dihydropyrimidine dehydrogenase deficiency\n- QT/QTc>450msec for men and >470msec for women\n- Patient with contraindication for trial drugs (investigators have to refer to SmPC drugs, see Appendix 7)\n- Concomitant intake of St. John's wort\n- Other concomitant cancer\n- Participation in another therapeutic trial\n- Pregnant woman or lactating woman\n- Patients with psychological, familial, sociological or geographical condition hampering compliance with the study protocol and follow-up schedule\n- Legal incapacity or limited legal capacity"}

Primary endpoints

• {"endpoint_text":"- Complete response rate where complete response is defined as complete disappearance of metastatic lesions after maximum of 12 cycles of chemotherapy and tumor marker level normalization (CEA). Complete disappearance of metastatic lesions will be assessed according to RECIST criteria version 1.1: Disappearance of all target and non-target lesions on the same method of assessment that at baseline (CT Scan or MRI). Every complete response will have to be confirmed 4 to 6 weeks after the last trt","definition_or_measurement_approach":"Complete disappearance of metastatic lesions after a maximum of 12 cycles and tumor marker (CEA) normalization; assessed according to RECIST v1.1 by disappearance of all target and non-target lesions using the same assessment method as baseline (CT scan or MRI). Every complete response must be confirmed 4 to 6 weeks after the last treatment."}

Secondary endpoints

• {"endpoint_text":"- Overall Survival (OS) is defined as the time from the date of randomization to the date of documented death from any cause","definition_or_measurement_approach":"Time from randomization to documented death from any cause."}
• {"endpoint_text":"- Progression-Free Survival (PFS) is defined as the time from the date of randomization to the date of documented progression or any cause of death. Progression will be assessed by CT scan or MRI according to RECIST criteria version 1.1","definition_or_measurement_approach":"Time from randomization to documented progression or death; progression assessed by CT or MRI per RECIST v1.1."}
• {"endpoint_text":"- Secondary resection rate is defined as the percentage of patients with initially irresectable metastases who will have a secondary resection R0 or R1 of their metastases","definition_or_measurement_approach":"Percentage of patients with initially unresectable metastases who undergo secondary R0 or R1 resection."}
• {"endpoint_text":"- Early tumor shrinkage (ETS) is defined as the relative change in the sum of longest diameters of RECIST target lesions after 4 cycles compared to baseline","definition_or_measurement_approach":"Relative change in the sum of longest diameters of RECIST target lesions after 4 cycles versus baseline."}
• {"endpoint_text":"- Depth of response (DpR) is defined as the relative change in the sum of longest diameters of RECIST target lesions at the nadir, in the absence of new lesions or progression of non-target lesions, as compared to baseline","definition_or_measurement_approach":"Relative change in the sum of longest diameters of RECIST target lesions at nadir compared to baseline, without new lesions or non-target progression."}
• {"endpoint_text":"- Adverse events rate will be graded based on NCI CTCAE v4.03 classification","definition_or_measurement_approach":"Adverse events graded using NCI CTCAE v4.03."}
• {"endpoint_text":"- Diagnostic performance of ccfDNA analysis compared to the tumor-tissue analysis (current gold standard)","definition_or_measurement_approach":"Comparison of diagnostic performance metrics (not further specified) between circulating cell-free DNA analysis and tumor tissue analysis (gold standard)."}

France

Earliest CTIS Part Ii Submission Date

29-02-2024

Latest Decision Or Authorization Date

22-03-2024

Processing Time Days

22

Number Of Sites

23

Number Of Participants

225

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"AMGEN","duties_or_roles":"Monetary support","organisation_type":""}