Two arm, prospective, multicenter randomized phase II trial of neoadjuvant modified Folfirinox regimen, with or without preoperative concomitant chemoradiotherapy in patients with borderline resectable pancreatic carcinoma.
Conditions
Interventions
Trade Name: Eloxatine
Pharmaceutical Form: Concentrate for solution for injection
Trade Name: Campto
Pharmaceutical Form: Concentrate for solution for injection
Trade Name: FLUOROURACILE PFIZER
Phar
Sponsors
Institut de Cancérologie de Lorraine Alexis Vautrin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ECOG performance status 0 or 1 Adult patients = 18 years and = 75 years of age Histologic or cytologic proven adenocarcinoma of the pancreas (histologic confirmation of diagnosis is preferred) Confirmation by independent multidisciplinary expert review of borderline resectable status, according to NCCN-Clinical Practice Guidelines in Oncology "pancreatic adenocarcinoma", version 1.2015. Adequate hematologic function, as follows: absolute neutrophil count (ANC) = 1.5 x 109/L platelet count = 100 x 109/L haemoglobin = 10 g/dL Adequate renal, hepatic and bone marrow function, defined as: Calculated creatinine clearance = 50 mL/min according to MDRD formula Serum total bilirubin = 1.5 times the institutional upper limit of normal. Patients with a biliary short metal stent due to cancer obstruction may be included provided that high-quality imaging is performed before stenting and bilirubin level after stent insertion decreased to = 20 mg/L (= 34 µmol/l), and there is no cholangitis. Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of study medication. Ability to provide written informed consent before the start of any study specific procedures Patient's legal capacity to consent to study participation and to understand and comply with the requirements of the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: Any previous treatment of the pancreatic cancer except biliary short metal stenting (chemotherapy, targeted tumor therapy, local ablative therapy, previous irradiation within the actual fields of planned radiotherapy) Evidence of distant metastases including ascites Evidence of extent of pancreatic cancer beyond that defined as "borderline resectable" : suspicious lymphadenopathy outside of the standard field of resection (i.e., aortocaval nodes, distant abdominal nodes) Contraindication for pancreas resection Pregnant or breast feeding females Patients with known Gilbert's Syndrome or homozygosity for UGT1A1*28 polymorphism Participation in any other clinical trial or treatment with any experimental drug within 28 days before enrolment to the study or during study participation until the end of treatment visit. Previous or concurrent malignant tumor disease other than underlying tumor disease (with the exception of cervical cancer in situ, adequately treated non-melanoma skin cancers, superficial bladder tumors (Ta, Tis, and T1) or any curatively treated without chemotherapy and favourable prognosis tumors without evidence of disease for > 3 years prior to enrolment) Any severe and/or uncontrolled medical conditions including but not limited to: Clinically significant cardiovascular or vascular disease : angina pectoris (even controlled), previous myocardial infarction, serious uncontrolled cardiac arrhythmia, chronic heart failure, cerebral infarction) Acute and chronic, active infectious disorders that requires systemic treatment Peripheral polyneuropathy > grade 1 Any previous inflammatory disease of colon or rectum Any other severe concomitant disease or disorder, which could influence patient's ability to participate in the study and his/her safety during the study e.g. severe hepatic, renal, pulmonary, metabolic, or psychiatric disorders Hypersensitivity against any of the study drugs (gemcitabine, oxaliplatin, irinotecan, 5-fluorouracil, folinic acid), or the ingredients of these drugs (e.g. fructose).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of two neoadjuvant therapies in patients with borderline resectable pancreatic carcinoma evaluated on histological R0 resection margin rate: induction chemotherapy with a modified FOLFIRINOX regimen (mFOLFIRINOX) consisted of oxaliplatin-irinotecan-fluorouracil-leucovorin. mFOLFIRINOX followed by a concomitant capecitabine-based chemoradiotherapy ;Secondary Objective: Evaluate the toxicities associated with chemotherapy and chemoradiotherapy Evaluate the proportion of resected patients. Evaluate the response rate to chemotherapy and chemoradiotherapy Evaluate the histological complete response rate in resected patients. Evaluate the perioperative mortality rate Evaluate the perioperative morbidity rate Evaluate the overall survival Evaluate the quality of life Evaluate the loco-regional relapse-free survival Evaluate the metastatic Progression Free Survival Evaluate the progression-free survival;Primary end point(s): Histological R0 resection rate in each treatment arm defined by the proportion of complete resection with no microscopic residual tumor (all margins should be negative with microscopic tumor clearance of at least 1 mm). Analysis will be performed in intent to treat population (ITT) in each arm.;Timepoint(s) of evaluation of this end point: post surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Toxicities associated with chemotherapy and chemoradiotherapy according to NCI-CTCAE v4.0 classification. Proportion of resected patients among all randomized patients. Response rate to chemotherapy and chemoradiotherapy evaluated by the RECIST 1.1 criteria (RECIST will not be considered for surgical intervention, except in case of evidence of progressive disease) Complete histological response defined by no residual cancer cells in tumor and in lymph node (ypT0N0) Perioperative death occurred during the hospitalization and within the 30 days following the end of the hospitalization Perioperative morbidity evaluated within the 30 days following the surgery according to Clavien-Dindo classification Overall survival (OS): defined as the time interval between the date of randomisation and the date of death (all causes) Quality of life measured by the EORTC QLQ-C30 questionnaire Loco-regional Relapse-Free Survival (LRFS) : defined as the time interval between the date of randomisation and the date of local relapse/recurrence or regional relapse/recurrence or death (all causes), whichever occurs first (DATECAN consensus definition for pancreatic cancer) Metastatic Progression Free Survival (mPFS): mPFS is defined as the time interval between between the date of randomisation and the date of metastases progression or occurrence of distant metastases (including liver or non-liver metastases) or death (all causes), whichever occurs first Progression-free survival (PFS): the time interval between the date of randomisation and the date of local or regional progression or metastases progression or occurrence of distant metastases (including liver or non-liver metastases) or occurrence of second pancreatic cancer or death (all causes), whichever occurs first (DATECAN consensus definition for pancreatic cancer) ;Timepoint(s) of evaluation of this end point: - at the end of the neoadjuvant mFOLFIRINOX treatment - at the end of the che | — |
Countries
France
Contacts
Public ContactVéronique GILLON
Institut de Cancérologie de Lorraine Alexis Vautrin
Outcome results
None listed