Gemcitabine Plus Nab-paclitaxel as Switch Maintenance Versus Continuation of Modified FOLFIRINOX as 1st Line Chemotherapy in Patients With Advanced Pancreatic Cancer.

PANThEON is a randomized, open-label, multicenter phase III trial aimed at comparing the switch maintenance with gemcitabine plus nab-paclitaxel (ARM B) versus mFOLFIRINOX continuation (ARM A) in terms of overall survival (OS) in patients with unresectable LAD or mPDAC without disease progression following 3 months of induction mFOLFIRINOX triplet chemotherapy.

Inclusion Criteria: * Patient able and willing to provide written informed consent and to comply with the study protocol. * Subjects must be ≥18 years. * Histologically or cytologically confirmed unresectable locally advanced or metastatic pancreatic adenocarcinoma eligible for treatment in the first-line setting. * Presence of measurable or non-measurable disease assessed by CT scan and/or MRI according to RECIST 1.1. Note: any lesion which has been subjected to percutaneous therapies or radiotherapy should not be considered measurable, unless the lesion has clearly progressed since the procedure. * Availability of archival tumor sample (primary tumor or metastatic site) for biomarker analysis. * ECOG performance status of 0-1 (if age \< 70 years). If age ≥70 years, ECOG PS must be 0. * Estimated life expectancy \> 3 months. * Adequate baseline hematologic function characterized by the following at screening: * Absolute Neutrophil Count (ANC) ≥ 1.5 × 109/L. * Platelets count ≥ 100 × 109/L. * Hemoglobin ≥ 9 g/dl. Note: prior transfusions for patients with low hemoglobin are allowed. * Adequate liver function characterized by the following at screening: * Serum total bilirubin ≤ 1.5 × ULN and \< 2 mg/dL. Note: Subjects with Serum total bilirubin ≥ 1.5 × ULN and conjugated bilirubin ≤ ULN or \< 40% of total bilirubin are allowed. * Serum transaminases (AST and/or ALT) \< 3 x ULN (\< 5 x ULN in presence of liver metastasis). In participants with elevated AST or ALT, the values must be stable for at least 2 week and with no evidence of biliary obstruction by imaging. * Adequate renal function, i.e. serum creatinine ≤ 1.5 x institutional ULN and calculated by Cockroft-Gault formula or directly measured creatinine clearance ≥ 50 mL/min. * Adequate coagulation functions as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). * No presence of complete dihydropyrimidine dehydrogenase (DPYD) enzyme deficiency (homozygous of the following DPYD polymorphisms: c1679GG, c1905+1AA, c2846TT) with DPYD gene testing mandatory at screening as per national guidelines. UDP-glucuronosyltransferase 1A1 (UGT1A1) testing is not mandatory. However, if UGT test is routinely performed in the participating centers, enrolment of patients carriers of variants of DPYD and homozygous variant UGT1A1 \[7/7\] has to be discussed with the Sponsor. * Women of childbearing potential must agree to remain abstinent (refrain from sexual intercourse) or use highly effective contraceptive methods, as defined in APPENDIX V of the full protocol, during the treatment period and for at least 7 months after the last administration of study treatments. * Negative serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women \ 9 months have elapsed from the last dose of therapy and documented disease progression or relapse. * Major surgery or radiation therapy performed within \ 2 weeks prior to start of study treatment. Patients must have recovered from an effect from major surgery. * Known allergy or hypersensitivity to study drugs and/or their excipients. * Unresolved toxicity ≥ CTCAE grade 2 attributed to any prior therapies (e.g. grade ≥2 peripheral neurotoxicity), excluding anemia or alopecia. * Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that requires directed therapy (such as radiotherapy or surgery) or increasing doses of corticosteroids 2 weeks prior to study entry. Participants with treated symptomatic brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study entry. * Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years prior to study entry except for curatively treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, and prostate cancer. * Know active uncontrolled hepatitis B or hepatitis C. Patients with a past or resolved HBV infection are eligible. Patients with chronic disease controlled by antiviral therapy or requiring prophylactic treatment are eligible. * Chronic or current active infectious disease requiring systemic antibiotics or antifungal treatment within 2 weeks prior to enrollment. * Known uncontrolled HIV infection. HIV-positive patients are eligible if their CD4+ cell count amounts to 300 cells per μL or more; HIV viral load must be undetectable per standard of care assay, and patients must be compliant with antiretroviral treatment. * Pregnant or breast-feeding patient, or patient planning to become pregnant within 7 months after the end of treatment. * Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA \> II, unstable angina pectoris, history of myocardial infarction within 3 months before study entry, significant arrhythmia). * Presence of psychiatric disorder precluding understanding of information of trial related topics and giving informed consent. * Any serious underlying medical conditions (judged by the investigator), that could impair the ability of the patient to participate in the trial.