PACLITAXEL for Borderline resectable pancreatic ductal adenocarcinoma|Pancreatic adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) defined by National Comprehensive Cancer Network (NCCN) criteria v2.2025 on contrast-enhanced CT-scan, with stage confirmed by a local pancreatic expert review board including at least medical oncologist/onco-gastroenterologist, pancreatic surgeon and pancreatic expert radiologist. No central review is required\n- Acceptation and ability to conform to the protocol requirement during all the duration of the investigation including treatment, scheduled visits, clinical and biological examinations and follow up\n- Women of childbearing potential must agree to use contraception during treatment and for at least 15 months after discontinuation of the experimental treatments. Men who have sexual relationship with women of childbearing potential must agree to use contraception during treatment and for at least 12 months after discontinuation of the experimental treatments\n- Patient affiliated to French social security\n- Adequate organ function, as defined by the following: o\tAST and ALT < 3.5 x upper limit of normal (ULN), o\tTotal serum bilirubin < 3 x ULN, (for patients with total serum bilirubin between 1.5 and 3 x ULN, the dose of irinotecan will be adjusted in accordance with the SmPC). o\tSerum albumin >30 g/L, o\tHemoglobin >9.0 g/dl, o\tAbsolute neutrophil count (ANC) >1.5 G/L, o\tPlatelets >100 G/L, o\tCreatinine clearance > 50 mL/min (according to CKD-EPI)\n- Measurable pancreatic lesion according to RECIST 1.1 (CT scan or MRI < 28 days),\n- WHO PS 1 or 0\n- Histologically proven pancreas ductal adenocarcinoma\n- Available FFPE from pancreatic tumor sample with > 10% of tumor cells (assessed by a local expert pancreatic pathologist)\n- No prior chemotherapy or radiation for pancreatic cancer (except one cycle of mFOLFIRINOX during waiting time for GEM + signature) or resection of pancreatic cancer\n- Age ≥18 years old and ≤ 80 years old if geriatric standardized evaluation validates the study chemotherapy regimen administration for patients between 75-80\n- Written informed consent obtained from patient before any protocol related intervention"}

Exclusion criteria

• {"criterion_text":"- Strictly resectable or locally advanced PDAC according to NCCN criteria\n- Known Gilbert's syndrome or known homozygosity for UGAT1A1*28 polymorphism\n- Treatment with millepertuis\n- Uncompensated asthma\n- Potentially severe infection < 7 days\n- Inflammatory bowel disease and/or intestinal obstruction\n- Known severe allergy to contrast dye (for CT or MRI) without possible substitution\n- Hypersensitivity to the active substance or to one of the excipients of one of the study treatments\n- Treatment with brivudine within 4 weeks prior to the administration of protocol treatment\n- Concomitant treatment with a strong inhibitor (i.e. ketoconazole) or inducer (i.e. rifampicin, carbamazepine, phenobarbital, phenytoin, apalutamide) of cytochrome P450 3A4 or 2C8 (CYP3A4 or CYP2C8)\n- Patient who has received a live attenuated vaccine (against yellow fever, chickenpox, shingles, measles, mumps, rubella, tuberculosis, rotavirus) in the 6 weeks prior to randomization\n- Distant metastases (including inter aortic lymph nodes)\n- Patient with sensitive peripheral neuropathy with functional discomfort\n- Impossibility of undergoing medical monitoring during the trial for geographical, social, or psychological reasons\n- Patient who is under judicial protection and patient who is legally institutionalized or under guardianship or not able to give consent\n- Any condition that contraindicates the use of IRINOTECAN, OXALIPLATIN, 5 FU, GEMCITABINE or NAB-PACLITAXEL\n- Partial or complete DPD deficiency (uracilemia ≥ 16 ng/mL)\n- Any progressive pathology not stabilized over the past 6 months: liver impairment, renal impairment, respiratory or cardiac failure\n- Other concomitant cancer or a history of cancer during the previous 3 years, except for localized cancer in situ, basal or squamous cell skin cancer adequately treated\n- Other interventional clinical trial except for non-interventional trial (ie not modifying 1-year EFS)\n- QT/QTc interval > 450 msec for men and > 470 msec for women\n- Pregnant or breastfeeding woman"}

Primary endpoints

• {"endpoint_text":"- 1-year EFS in the GEM + randomized population","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- ORR is defined as % of patients with a complete or a partial response","definition_or_measurement_approach":"Defined as percentage of patients with a complete or partial response"}
• {"endpoint_text":"- TRG evaluated by Ryan Simplified TRG on the primary tumor after surgery.","definition_or_measurement_approach":"Tumor Regression Grade evaluated by Ryan Simplified TRG on the primary tumor after surgery"}
• {"endpoint_text":"- Resection rates will be evaluated after 4 months of neoadjuvant chemotherapy in both arms","definition_or_measurement_approach":"Resection rates assessed after 4 months of neoadjuvant chemotherapy"}
• {"endpoint_text":"- OS is defined as the time between the date of randomization and the date of death (whatever the cause)","definition_or_measurement_approach":"Overall Survival: time from randomization to death from any cause"}
• {"endpoint_text":"- PFS is defined as the time between the date of randomization and the date of first recurrence or death (all causes). PFS will be evaluated on patients without resection","definition_or_measurement_approach":"Progression-Free Survival: time from randomization to first recurrence or death; evaluated for patients without resection"}
• {"endpoint_text":"- DFS is defined as the time between the date of randomization and the date of first recurrence or death. DFS will be evaluated on patients with resection","definition_or_measurement_approach":"Disease-Free Survival: time from randomization to first recurrence or death; evaluated for patients with resection"}
• {"endpoint_text":"- TTR is defined as the time between the date of randomization and the date of first recurrence or death linked to the cancer","definition_or_measurement_approach":"Time To Recurrence: time from randomization to first recurrence or death linked to the cancer"}
• {"endpoint_text":"- Percentage of NAC completion (4 months planned) is defined as the percentage of patients who received the 4 cycles of NAC","definition_or_measurement_approach":"Percentage of patients who received the planned 4 cycles of neoadjuvant chemotherapy"}
• {"endpoint_text":"- Percentage of adjuvant chemotherapy is defined as the percentage of patients who received at least one dose of adjuvant chemotherapy","definition_or_measurement_approach":"Percentage of patients receiving at least one dose of adjuvant chemotherapy"}
• {"endpoint_text":"- Toxicities during the NAC will be collected before each NA cycle and will be graded according to NCI-CTCAE v5.0","definition_or_measurement_approach":"Toxicities collected before each neoadjuvant cycle and graded per NCI-CTCAE v5.0"}
• {"endpoint_text":"- Quality of life will be assessed with QLQC30 and QLQPAN26. It is defined as the time between the date of randomization and the date of death or date of first deterioration by more than five points on the global health scale in comparison with the score at baseline","definition_or_measurement_approach":"Quality of life assessed with QLQ-C30 and QLQ-PAN26; defined as time from randomization to death or first deterioration >5 points on global health scale vs baseline"}

France

Earliest CTIS Part Ii Submission Date

05-09-2025

Latest Decision Or Authorization Date

17-10-2025

Processing Time Days

42

Number Of Sites

26

Number Of Participants

110

Primary sponsor

Full Name

Fondation Franc.Cancerologie Digestive

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France