FLUOROURACIL for Pancreatic adenocarcinoma

Inclusion criteria

• {"criterion_text":"- 1. Signed and dated informed consent, and willing and able to comply with protocol requirements,\n- 10. Adequate renal function: serum creatinine level <150μM and estimated creatinine clearance >30ml/min,\n- 11. Adequate liver function: AST (SGOT) and ALT (SGPT) ≤2.5xULN (≤5xULN in case of liver metastases),\n- 12. Total bilirubin ≤3 x ULN,\n- 13. QT / QTc interval at baseline ECG (performed within 1 month before randomization) < than 450 msec for men and < than 470 msec for women,\n- 14. Baseline evaluations performed before randomization: clinical and blood evaluations no more than 2 weeks (14 days) prior to randomization, tumor assessment (CT-scan or MRI, evaluation of non-measurable lesions) no more than 28days prior to randomization,\n- 15. Female patients must be surgically sterile, or be postmenopausal, or must commit to using reliable and appropriate methods of contraception during the study and during at least six months after the end of study treatment (when applicable). All female patients with reproductive potential must have a negative pregnancy test (β HCG) within 7 days prior to starting protocol treatment. Breastfeeding is not allowed.\n- 16. Male patients must agree to use effective contraception in addition to having their partner use a contraceptive method as well during the trial and during at least six months after the end of the study treatment\n- 17. Affiliation to a French social security system (recipient or assign).\n- 2. Histologically or cytologically proven adenocarcinoma of the pancreas,\n- 3. In absence of histologically or cytologically proven adenocarcinoma, a cluster of clinical, biological and radiological arguments consistent with the diagnosis: among these, a hypodense pancreatic tumor at CT and a Ca 19-9 greater than 500 UI/ml are essential prerequisites,\n- 4. Metastatic disease confirmed (stage IV),\n- 5. No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy and relapse must be >12 months),\n- 6. Age ≥18 years,\n- 7. Patient non-fit for FOLFIRINOX with ECOG performance status (PS) 0-2,\n- 8. For patients with ECOG performance status (PS) = 2, an albuminemia level >25 g/l is required,\n- 9. Haematological status: neutrophils (ANC) >2x109/L; platelets >100x109/L; haemoglobin ≥9g/dL,"}

Exclusion criteria

• {"criterion_text":"- 1. History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),\n- 10. Treatment with any other investigational medicinal product within 28 days prior to study entry,\n- 11. Other serious and uncontrolled non-malignant disease (eg. active infection requiring systemic therapy, coronary stenting or myocardial infarction or stroke in the past 6 months),\n- 12. Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C,\n- 13. Known uncontrolled bacterial infection\n- 14. History or active interstitial lung disease (ILD),\n- 15. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years, iv/ malignancy with indolent evolution not requiring treatment,\n- 16. Patients with known allergy to active substance or any excipient of study drugs,\n- 17. Allergy to iodinated contrast product\n- 18. Concomitant administration of live, attenuated virus vaccine and concomitant administration of prophylactic phenytoin.\n- 19. Patients under legal protection or unable to consent\n- 2. Local or locally advanced disease (stage I to III),\n- 20- Participation in another interventional research (medical treatment or medical device).\n- 3. Patient uses warfarin or other antivitamin k,\n- 4. Patient receiving concomitant radiotherapy,\n- 5. Electrolytic report uncontrolled: hypercalcemia and/or hypokalemia and/or hypomagnesemia,\n- 6. Pre-existing permanent neuropathy (NCI grade ≥2),\n- 7. Poor nutritional status (albuminemia level ≤ 25 g/l)\n- 8. Known dihydropyrimidine dehydrogenase (DPD) total or partial deficiency (controlled before inclusion by DPD genotypage or uracilemia dosage whatever the anteriority),\n- 9.Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),"}

Primary endpoints

• {"endpoint_text":"- Overall survival (OS) at 24 months","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Objective response rate and disease control rate (RECIST criteria 1.1), duration of response, duration of disease control.","definition_or_measurement_approach":"Tumor response assessed using RECIST criteria 1.1 (as stated)."}
• {"endpoint_text":"- Progression-free survival (PFS) will be defined as the delay between the date of inclusion and the date of the first event (progression or death) or date of last news if the patient is alive without any progression.","definition_or_measurement_approach":"PFS defined in text: time from date of inclusion to first event (progression or death) or date of last contact if alive without progression."}
• {"endpoint_text":"- Ca 19-9 and CEA levels, at inclusion and their dynamic change under treatment.","definition_or_measurement_approach":"Serial measurement of CA 19-9 and CEA levels at inclusion and during treatment to assess dynamic changes (as stated)."}
• {"endpoint_text":"- Toxicities will be described by type of toxicities and grades according to International Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.","definition_or_measurement_approach":"Adverse events graded by CTCAE version 5.0 (type and grade reported)."}
• {"endpoint_text":"- Safety: rate of serious adverse events, grade 3-4 toxicities (hematologic and non-hematologic). Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.","definition_or_measurement_approach":"Safety measured as rates of SAEs and grade 3-4 toxicities; grading per NCI CTCAE v5.0."}
• {"endpoint_text":"- Quality of life will be studied by means of the EORTC QLQ C-30 questionnaire, the health-related quality of life (HRQoL) and the consensual geriatric minimum data set (SOFOG) for patients ≥75 years and","definition_or_measurement_approach":"Quality of life assessed using the EORTC QLQ-C30 and HRQoL instruments; SOFOG geriatric data set for patients ≥75 years (as stated)."}
• {"endpoint_text":"- The dose-intensity (DI) of each protocol will be calculated based on the number of cycles received by each patient. The relative DI will be calculated as the ratio of the DI to the DI indicated in the protocol (obtained as the dose specified per cycle in mg/m²).","definition_or_measurement_approach":"DI calculated from number of cycles received; relative DI = observed DI / protocol-specified DI (dose per cycle in mg/m²) (as stated)."}
• {"endpoint_text":"- The Quality-adjusted Time WIthout Symptoms of disease or Toxicity (Q-TWIST)","definition_or_measurement_approach":"Q-TWIST analysis as named; no further definition provided in text."}
• {"endpoint_text":"- Type of second-line and third-line regimens and the date of beginning of first-cycle of each line will be collected.","definition_or_measurement_approach":"Collection of subsequent-line regimen types and start dates (as stated)."}

France

Earliest CTIS Part Ii Submission Date

07-08-2024

Latest Decision Or Authorization Date

03-03-2025

Processing Time Days

208

Number Of Sites

48

Number Of Participants

400

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France