LEVOLEUCOVORIN for Resected pancreatic adenocarcinoma

Inclusion criteria

• {"criterion_text":"- 1.\tHistologically confirmed resected pancreatic adenocarcinoma (R0 or R1) who received 3 months of neoadjuvant mFOLFIRINOX, including anatomically resectable and borderline resectable tumors, in accordance with the definitions and therapeutic considerations provided in the TNCD (2024), and ESMO (2023) guidelines."}
• {"criterion_text":"- 2.\tPerformans status ECOG 0 or 1"}
• {"criterion_text":"- 3.\tCA 19-9 level ≤ 200 U/ml"}
• {"criterion_text":"- 4.\tAge 18 or over"}
• {"criterion_text":"- 5.\tAbsolute neutrophil count > 1,500 mm3 platelet count > 100,000 mm3 creatinine clearance (according MDRD equation) > 50 ml/min, haemoglobin level > 10 g/dl (transfusions are authorized)"}
• {"criterion_text":"- 6.\tWomen of childbearing potential (a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile): - with highly effective contraception (Cf. CTCG) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence) since 1 month, during chemotherapy treatment and for 15 months after cessation of chemotherapy treatment and, -\ta negative blood pregnancy test by B-HCG at inclusion as well as pregnancy tests before each cycle of adjuvant chemotherapy, then monthly throughout the study until 15 months after the end of exposure to systemic treatmentand. •\tWomen permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) •\tPostmenopausal women: A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient."}
• {"criterion_text":"- 7.\tFor men participating in the study, contraception is required during the trial and for 12 months after stopping chemotherapy treatment."}
• {"criterion_text":"- 8.\tPatient affiliated with, or beneficiary of a social security (national health insurance) plan"}
• {"criterion_text":"- 9.\tPatient able to comply with the study protocol, in the investigator’s judgment"}
• {"criterion_text":"- 10.\tRead and understood the information letter and signed the consent form"}

Exclusion criteria

• {"criterion_text":"- 1.\tMetastatic PAC on post-operative imaging"}
• {"criterion_text":"- 2.\tCholangiocarcinoma, ampullary carcinoma or other Non PAC pancreatic tumors"}
• {"criterion_text":"- 3.\tNon-controlled congestive heart failure – non-treated angina; recent myocardial infarction (In the previous year) – non-controlled AHT (SBP >160 mm or DBP > 100 mm, despite optimal drug treatment), long QT"}
• {"criterion_text":"- 4.\tMajor non-controlled infection, chronic infectious diseases, immune deficiency syndromes"}
• {"criterion_text":"- 5.\tPremalignant hematologic disorders, e.g. myelodysplastic syndrome"}
• {"criterion_text":"- 6.\tSevere liver failure"}
• {"criterion_text":"- 7.\tPast or current history of malignancies except for the indication under this study and curatively treated Basal and squamous cell carcinoma of the skin, In-situ carcinoma of the cervix, Other malignant disease without recurrence after at least 2 years of follow-up"}
• {"criterion_text":"- 8.\tAny medical, psychological or social situation that (in the investigator's opinion) could limit the patient's compliance with the protocol or the ability to obtain or interpret data or to understand the conditions required for his/her participation to the protocol or unable him/her to give an informed consent"}
• {"criterion_text":"- 9.\tPregnant or breastfeeding women and women of child-bearing age not using effective means of contraception"}
• {"criterion_text":"- 10.\tPerson participating to another interventional research having the same primary endpoint"}
• {"criterion_text":"- 11.\tPerson deprived of liberty by an administrative or judiciary decision or person placed under judicial protection, under guardianship or curatorship"}
• {"criterion_text":"- 12.\tUracilemia ≥ 150 ng/ml (suggestive of complete DPD deficiency)"}
• {"criterion_text":"- 13.\tContraindication to study adjuvant chemotherapy treatments in accordance with the SmPC’s of the products used in this trial (Gemcitabine, Nab-Paclitaxel, Oxaliplatin, Folinic Acid or Leucovorin, Irinotecan, Fluorouracil)"}

Primary endpoints

• {"endpoint_text":"- Phase 2: The primary efficacy endpoint is the Disease Free Survival (DFS), defined as the time from randomization to locoregional recurrence, occurrence of distant metastases or second pancreatic cancer, or death (all causes) whichever occurred first. Patients free of events will be censored at the date of the last disease evaluation either during study treatment period or during follow-up period (1,53).","definition_or_measurement_approach":"Defined as the time from randomization to locoregional recurrence, occurrence of distant metastases or second pancreatic cancer, or death (all causes), whichever occurs first. Patients free of events will be censored at the date of the last disease evaluation either during study treatment period or during follow-up period."}
• {"endpoint_text":"- Phase 3: The primary efficacy endpoint is the Overall Survival (OS), defined as the time from randomization to the death from any cause. Alive patient will be censored at last date known to be alive either during study treatment period or during follow-up period","definition_or_measurement_approach":"Defined as the time from randomization 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."}

Secondary endpoints

• {"endpoint_text":"- •\tIncidence and grade for Adverse events (AEs), drug related AEs, drug related AE leading to dose reduction or discontinuation during treatment, SAE and SUSAR, according to NCI-CTCAE V5.0.","definition_or_measurement_approach":"Incidence and grade of AEs, drug-related AEs, AEs leading to dose reduction or discontinuation, SAEs and SUSARs will be collected and graded according to NCI-CTCAE v5.0."}
• {"endpoint_text":"- •\tOS (phase 2)","definition_or_measurement_approach":"Overall Survival in the phase 2 step (time from randomization to death from any cause)."}
• {"endpoint_text":"- •\tDFS (Phase 3)","definition_or_measurement_approach":"Disease-Free Survival in the phase 3 step (time from randomization to locoregional recurrence, distant metastases, second pancreatic cancer, or death)."}
• {"endpoint_text":"- •\tTime to metastatic recurrence defined as the time from randomization to occurrence of distant metastases. Patients with locoregional recurrence, second pancreatic cancer, or death (all causes) without metastatic recurrence will be censored at time of event whichever occurred first. Patients free of locoregional recurrence, second pancreatic cancer, or death (all causes) without metastatic recurrence will be censored at the date of the last disease evaluation","definition_or_measurement_approach":"Defined as time from randomization to occurrence of distant metastases. Patients with other events without metastatic recurrence are censored at time of that event; patients without events are censored at last disease evaluation."}
• {"endpoint_text":"- •\tEarly recurrence < 6 months after surgical randomization","definition_or_measurement_approach":"Proportion or incidence of recurrence occurring within 6 months after surgical randomization."}
• {"endpoint_text":"- •\tHealth related quality of life EORTC QLQ-C30 and QLQ-PAN26 questionnaires","definition_or_measurement_approach":"Health-related quality of life assessed using EORTC QLQ-C30 and QLQ-PAN26 questionnaires."}
• {"endpoint_text":"- •\tTumour response and clinico-pathological criteria (size (T stage); margins (R0/R1 status); lymph node invasion (N stage)), DFS and OS","definition_or_measurement_approach":"Tumour response and clinicopathological criteria (T stage, R0/R1 margins, N stage) will be associated with DFS and OS; measurement by pathological analysis and standard staging criteria."}

France

Earliest CTIS Part Ii Submission Date

18-04-2025

Latest Decision Or Authorization Date

28-05-2025

Processing Time Days

40

Number Of Sites

37

Number Of Participants

390

Primary sponsor

Full Name

Centre Hospitalier Universitaire Rouen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France