“NALPAC” 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.

Prior treatment

• Uncontrolled concurrent CNS, cardiac, infectious diseases, hypertension
• Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to the first dose of treatment
• Patients receiving or having received any investigational treatment within 4 weeks prior to the first dose of treatment, or participating to another clinical study
• The following drugs are noted as interacting with Pegylated liposomal irinotecan (in combination with 5-FU and LV, in patients who have progressed following gemcitabine-based therapy), and are therefore excluded from the study: Live or live-attenuated vaccines in patients immunocompromised by chemotherapy, strong CYP3A4 inducers such as anticonvulsants (phenytoin, phenobarbital or carbamazepine), rifampin, rifabutin and St. John’s wort. Strong CYP3A4 inhibitors (e.g. grapefruit juice, clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole and ketoconazole). Strong CYP3A4 inhibitors should be discontinued at least 1 week prior to starting ONIVYDE pegylated liposomal therapy. Strong UGT1A1 inhibitors (e.g. atazanavir, gemfibrozil, indinavir, regorafenib)

Other illness

• Liver failure, cirrhosis Child Pugh B or C
• Active chronic hepatitis B or C with a need for antiviral treatment
• History of organ allograft
• Ongoing uncontrolled, serious infection
• Renal failure requiring dialysis
• History of myocardial infarction, deep venous or arterial thrombosis, CVA during the last 6 months
• Known hypersensitivity to any of the components of study treatments
• Previous malignancy in the last past 3 years except basal cell cancer of the skin, pre-invasive cancer of the cervix or carcinoma in situ of any type
• 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

Other

• Complete DPD deficiency
• Brain metastasis
• Pregnancy or breast feeding

• Histologically proven metastatic adenocarcinoma of the pancreas
• Effective contraception for both male and female patients if the risk of conception exists
• Peripheral Neuropathy < grade 2
• Progression documented after first line treatment with Gemcitabine-Abraxane or gemcitabine alone
• 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