Phase I/II Study to Evaluate Nab-paclitaxel in Substitution of CPT11 or Oxaliplatin in FOLFIRINOX Schedule as First Line Treatment in Metastatic Pancreatic Cancer
Condition: Metastatic Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Paclitaxel bound albumine
Intervention type(s): Drug
Other intervention name(s): nab-paclitaxel
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: mPC