At this moment, FOLFIRINOX is the best treatment for selected patients (pts) with metastatic pancreatic cancer (mPC). Investigator would like to evaluate the substitution of CPT11 or Oxaliplatin in FOLFIRINOX schedule with Nab-paclitaxel (Nab-p) [Nab-FOLFIRI and Nab-FOLFOX].

Doses for Nab-FOLFIRI and Nab-FOLFOX will be determined by the phase I trial. One or both schedules will be evaluated in successive phase II part.

The primary objective for phase I of the study is to determine the MTD of Nab-p when used in substitution of OXA or CPT11 in FOLFIRINOX schedule, as first-line treatment in pts with mPC. The dose finding strategy will be based on the classical 3+3 dose escalation design.

-Analysis sets: Modified intention-to-treat population: it consists of all pts who are allocated and receive at least one dose of any component of study treatment. Pts will be grouped according to the randomized treatment assignment. Pts treated during the phase I step will be not included in this population.

Safety population: it consists of all pts who are allocated and receive at least one dose of any component of study treatment. Groups are defined by the study treatment actually received. Pts treated at the MTD during the phase I step will be not included in this population.

Statistical methods Best ORR will be summarized and 95% confidence limits will be calculated according to the exact method for each of the treatment arms included in the phase II step.

All the analyses of primary and secondary efficacy variables will be performed on the modified intention-to-treat population.

The overall incidences of AEs will be summarized. Pts who experienced the same event on more than one occasion are counted only once in the calculation of the event frequency, at the highest intensity ever observed.

Serious adverse events will be summarized. All the safety analyses will be performed on the safety population.

-Sample size: The experimental treatment, to be considered clinically worthwhile, should determine an overall best RR equal to or greater than 40%. According to the Fleming single stage design, for a 90% power towards an alternative hypothesis of an ORR equal to or greater than 40% and a one-sided type I error rate of 5%, respect to the null hypothesis of an ORR equal to or less than 20%, 42 pts must be included in the final evaluation, in each arm of the phase II step. According to the exact binomial test, the experimental treatment will be considered sufficiently promising and candidate to further studies in the case of a major objective response is seen in at least 14 pts.

Inclusion Criteria:

• . Males or females ≥ 18 years old and ≤ 75 years old;
• Histological or cytological evidence of a diagnosis of pancreatic ductal adenocarcinoma;
• Written informed consent prior to any study-specific procedures; 4. Measurable metastatic disease, defined in according to RECIST Version 1.1 (Eisenhower et al. 2009), that had not previously been treated with CT for metastatic disease;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 ;
• Absence of previous abdominal radiotherapy on target lesions (except radiation therapy analgesic if it has not been performed on measurable targets);
• Absence of heart failure or angina or infarction within 12 months previous inclusion;
• Have adequate organ function including:

Hematologic: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L.

Hepatic: Bilirubin ≤ 1.5 times upper limits of normal (ULN) (Pts may have endoscopic or radiologic stenting to treat biliary obstructions).

Renal: Serum creatinine within normal limits ≤1.5 times ULN.

Exclusion Criteria:

• Age of 76 years or older;
• Endocrine or acinar pancreatic carcinoma;
• Previous radiotherapy for measurable lesions;
• Central nervous system metastasis;
• Other concomitant cancer or history of cancer outside a carcinoma in situ of the cervix or basal or squamous cell of the skin;
• Pts already included in another clinical trial with other experimental drugs;
• Current active infection;
• Have serious pre-existing medical conditions or serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator (for example, unstable angina pectoris, or a clinically significant history of cardiac disease or uncontrolled diabetes mellitus);
• Females who are pregnant or lactating;
• Unable to undergo medical test for geographical, social or psychological reason
• Known dihydropyrimidine dehydrogenase (DPD) deficiency