D,L-LYSINE ACETYLSALICYLATE for Metastatic colorectal cancer|Chemo-resistant metastatic colorectal cancer

Inclusion criteria

• {"criterion_text":"- 1.\tPatients with histologically proven metastatic colorectal cancer in progression after previous standard treatments (5FU, CPT11, oxaliplatin, anti-VEGF, trifluridine/tipiracil, and anti-EGFR therapy if KRAS and NRAS WT, anti-BRAF therapy if BRAF V600E mutated, and anti-PD1 if MSI-H/dMMR tumor), or not considered as candidate for these treatments."}
• {"criterion_text":"- 10.\tNo contraindication to Iodine contrast media injection during CT"}
• {"criterion_text":"- 11.\tFor female patients of childbearing potential, negative pregnancy test within 14 days before starting the study drug. Men and women are required to use adequate birth control during the study (when applicable),"}
• {"criterion_text":"- 2.\tSigned and dated informed consent,"}
• {"criterion_text":"- 3.\tAbility to comply with the study protocol, in the Investigator’s judgment."}
• {"criterion_text":"- 4.\tRegistration in a national health care system (CMU included)."}
• {"criterion_text":"- 5.\tLife expectancy of at least 3 months"}
• {"criterion_text":"- 6.\tFemale or male with age >18 years old"}
• {"criterion_text":"- 7.\tPerformance status = 0 or 1 (Annex 1)"}
• {"criterion_text":"- 8.\tMeasurable disease defined according to RECIST v1.1 guidelines (scanner or MRI) (Annex 2)"}
• {"criterion_text":"- 9.\tAdequate bone marrow, liver and renal functions: Haemoglobin ≥ 9 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, Total serum bilirubin ≤ 1.5 times upper normal value (ULN), serum alkaline phosphatase < 5 times ULN, aminotransferases (AST/ALT) ≤ 3 × ULN in absence of hepatic metastasis or ≤ 5 if presence of hepatic lesions, Cockcroft glomerular filtration rate > 50 ml/min, Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour"}

Exclusion criteria

• {"criterion_text":"- 1.\tDiagnosis of additional malignancy within 2 years prior to the inclusion (exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical and/or bladder cancer),"}
• {"criterion_text":"- 10.\tKnown hypersensitivity to any of the study drugs, study drug classes or excipient in the formulation: -\tHistory of severe and unexpected reactions to fluoropyrimidine therapy, -\tHistory of asthma induced by the administration of salicylates or substances with a similar action, notably non-steroidal anti-inflammatory medicines, -\tMastocytosis, for whom the use of acetylsalicylic acid can cause severe hypersensitivity reactions,"}
• {"criterion_text":"- 11.\tUnresolved toxicity higher than CTCAE (v5) Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neuropathy ≤ Grade 2,"}
• {"criterion_text":"- 12.\tSubject unable to swallow oral medications or any malabsorption condition,"}
• {"criterion_text":"- 13.\tInadequate organ functions: -\tknown cardiac failure of unstable coronaropathy, respiratory failure, or uncontrolled infection or another life-risk condition -\tCongestive Heart Failure ≥ New York Heart Association (NYHA) class 2, -\tMyocardal infarction less than 6 months before start of study drug, unstable angina (anginal symptoms at rest), new-onset angina (begun within the last 3 months), Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted), -\tUncontrolled hypertension (defined by systolic blood pressure ≥ 150 mmHg and/or diastolic pressure ≥ 100 mmHg despite optimal medical management), or history of hypertensive crisis, or hypertensive encephalopathy -\tPleural effusion or ascites that causes respiratory compromise (≥ CTCAE grade 2 dyspnea), -\tInterstitial lung disease with ongoing signs or symptoms, -\tOngoing infection >grade 2 CTCAE V5, -\tDehydration CTCAE v5 grade ≥1, -\tUrinary tract obstruction"}
• {"criterion_text":"- 14.\tConstitutional or acquired hemorrhagic disease: -\tAny haemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication, -\tHistory of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to inclusion, -\tSerious, Non-healing wound, active peptic ulcer or untreated bone fracture, -\tMajor surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication,"}
• {"criterion_text":"- 15.\tPlanned surgical procedure within the first month of treatment or any procedure that might change the timing of regorafenib administration during the first month of treatment,"}
• {"criterion_text":"- 16.\tKnown History of human immunodeficiency virus (HIV) infection; Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy,"}
• {"criterion_text":"- 17.\tReceipt of yellow fever vaccine within 28 days prior to study,"}
• {"criterion_text":"- 18.\tHistory of organ allograft,"}
• {"criterion_text":"- 19.\tPregnant or breast-feeding subjects"}
• {"criterion_text":"- 2.\tCurrent participation in a study of an investigational agent or in the period of exclusion"}
• {"criterion_text":"- 3.\tAny psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before inclusion in the trial ;"}
• {"criterion_text":"- 4.\tPatient under judicial protection (curatorship, tutorship) and/or deprived of freedom,"}
• {"criterion_text":"- 5.\tPrevious exposition to regorafenib or anti-angiogenic treatment other than bevacizumab and aflibercept"}
• {"criterion_text":"- 6.\tTreatment with any other investigational medicinal product within 28 days prior to study entry, EXCEPT for ASPIRIN,"}
• {"criterion_text":"- 7.\tSystemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 3 weeks,"}
• {"criterion_text":"- 8.\tChronic treatment with drug potentially interacting with regorafenib i.e. CYP3A4, CYP2C9 or UGT1A9 inductor/inhibitor; Epilectic disorder requiring medication; Recent or concomitant treatment with brivudine,"}
• {"criterion_text":"- 9.\tComplete deficit in dihydropyrimidine deshydrogenase (DPD),"}

Primary endpoints

• {"endpoint_text":"- Progression-free survival (PFS): defined as the time from the randomization date to disease progression as per RECIST v1.1 or death from any cause, whichever occurs first. Alive patients without progression will be censored at last radiological evaluation available in the study arms treatment setting showing no progression.","definition_or_measurement_approach":"PFS defined as time from randomization to disease progression per RECIST v1.1 or death; alive patients without progression censored at last radiological evaluation in study treatment setting."}

Secondary endpoints

• {"endpoint_text":"- Health related Quality of life : - EORTC QLC30 + CR29, EQ-5D-5L questionnaires - 5 prespecified targeted dimensions of interest : Global health/ Pain/ Physical Functioning / Fatigue / Emotional Functioning - Number of days of hospitalization","definition_or_measurement_approach":"QoL measured by EORTC QLQ-C30+CR29 and EQ-5D-5L; time to definitive deterioration in five targeted dimensions (Global health, Pain, Physical Functioning, Fatigue, Emotional Functioning); number of days hospitalized."}
• {"endpoint_text":"- Toxicities graded according to NCI-CTCAE criteria version","definition_or_measurement_approach":"Toxicities graded according to NCI-CTCAE (v5 referenced in translations)."}
• {"endpoint_text":"- Overall survival (OS): defined as the time from the randomization date to death from any cause. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period.","definition_or_measurement_approach":"OS defined as time from randomization to death from any cause; alive patients censored at last known alive date."}
• {"endpoint_text":"- Disease control rate (DCR): DCR is defined as the proportion of participants with best overall response of confirmed CR or PR or stable disease (SD).","definition_or_measurement_approach":"DCR = proportion of participants with confirmed CR, PR or SD as best overall response."}
• {"endpoint_text":"- Duration of objective response (DOR): defined as the time from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (if death occurs before progression is documented). DOR will be defined for responders only, i.e. patients with a CR or PR. The actual dates the tumor scans were performed will be used for this calculation. DOR for patients who have not progressed or died at the time of analysis will be censored at the date of last TM","definition_or_measurement_approach":"DOR = time from first documented PR or CR to progression or death; defined for responders only; actual tumor scan dates used; censoring at last tumor measurement if no progression/death."}
• {"endpoint_text":"- Evaluation of CHUN morphological criteria","definition_or_measurement_approach":"Assessment of CHUN radiological morphological criteria and correlation with RECIST v1.1 response."}
• {"endpoint_text":"- Economic evaluation: incremental cost-utility ratio: EuroQol-5D-5L (EQ-5D-5L) questionnaire and VAS (repeated measures at baseline, W8, M4, M6, M8, M10, M12 and end of study M18)","definition_or_measurement_approach":"Economic evaluation via incremental cost-utility ratio using EQ-5D-5L and VAS at specified timepoints (baseline, W8, M4, M6, M8, M10, M12, M18)."}

France

Earliest CTIS Part Ii Submission Date

21-03-2024

Latest Decision Or Authorization Date

19-02-2026

Processing Time Days

700

Number Of Sites

13

Number Of Participants

174

Primary sponsor

Full Name

Centre Hospitalier Regional Universitaire

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France