a study evaluating the efficacy of 5-fu + naliri and 5-fu + nalirinox for pdac (nalpac)

Conditions: Metastatic Pancreatic Ductal Adenocarcinoma

Summary: a non-comparative randomized phase 2 study, evaluating the efficacy of 5-fu + naliri and 5-fu + nalirinox for metastatic pancreatic ductal adenocarcinoma (pdac), progressive after gemcitabine-abraxane or gemcitabine monotherapy

based on the results of previous studies, the sponsor aims to assess efficacy and safety of this triplet (irinotecan, 5fu/lv and oxaliplatin) in second-line treatment in fit patients (ecog 0-1) metastatic pdac. the primary objective is to assess the efficacy of nalirinox (= investigational arm) and naliri (= standard care arm) in terms of progression-free survival rate (pfsr). as secondary objectives, the following will be evaluated in both arms: * safety/toxicity and tolerability profile according to the national cancer institute (nci) common terminology criteria for adverse events (ctcae), version 5. * progression free survival (pfs) * overall response rate and duration of response as assessed by imaging (recist 1.1) and tumor markers * overall survival (os)

Eligibility criteria:
inclusion criteria: * histologically proven metastatic adenocarcinoma of the pancreas * progression documented after gemcitabine-abraxane, or gemcitabine monotherapy * signed written informed consent * age ≥ 18 * ecog ps 0/1 at study entry * measurable disease * adequate renal (serum creatinine ≤ 1.5x upper reference range), liver (total bilirubin ≤ 1.5x upper reference range) and hematopoietic functions (pmn ≥ 1,5x109/l, platelets ≥ 100x109/l, hemoglobin ≥ 9g/dl) * inr/ptt ≤ 1.5x uln * life expectancy of at least 12 weeks * effective contraception for both male and female patients if the risk of conception exists during treatment and for one month after the last administration * peripheral neuropathy \< grade 2 exclusion criteria: * uncontrolled concurrent cns, cardiac, infectious diseases, hypertension * history of myocardial infarction, deep venous or arterial thrombosis, cva during the last 6 months * known hypersensitivity to any of the components, including excipients, of study treatments * previous malignancy in the last past 3 years except basal cell cancer of the skin or preinvasive cancer of the cervix or carcinoma in situ of any type * pregnancy or breast feeding * medical or psychological conditions that would not permit the patient to complete the study or sign inform consent * unstable angina, congestive heart failure ≥nyha class ii * uncontrolled hypertension despite optimal management (systolic blood pressure \>150 mmhg or diastolic pressure \> 90mmhg) * hiv infection * complete dpd deficiency * liver failure, cirrhosis child pugh b or c * active chronic hepatitis b or c with a need for antiviral treatment * brain metastasis * major surgery, open biopsy or significant traumatic injury within 4 weeks prior to the first dose of treatment * history of organ allograft * ongoing uncontrolled, serious infection * renal failure requiring dialysis * patients receiving or having received any investigational treatment within 4 weeks prior to study entry, or participating to another clinical study