A Phase I-II Study of PAXG in Stage III-IV Pancreatic Adenocarcinoma
OBJECTIVES: PHASE I: to determine the recommended phase 2 dose of nab-paclitaxel in
combination with cisplatin, capecitabine, and gemcitabine.
PHASE II: to evaluate the feasibility and the activity of the PAXG regimen in terms of
6-months progression-free survival in patients with stage III and IV pancreatic cancer.
OUTLINE Phase I - dose finding single institution trial, followed by a randomized open label
multicenter phase II trial.
Phase II: Patients will be stratified by stage (III vs IV) and CA19.9 level (< 10 x ULN
versus >10 x ULN); Patients will be randomly assigned to receive PAXG (arm A) or PEXG
regimen (arm B).
Treatment plan (phase II):
Arm A: PAXG every 4 weeks (1 cycle): cisplatin at 30 mg/m2 on days 1 and 15, nab-paclitaxel
at the RP2D on days 1 and 15, capecitabine at 1250 mg/ m2 days 1-28, gemcitabine at 800 mg/
m2 on days 1 and 15.
Arm B: PEXG every 4 weeks (1 cycle): same as above for cisplatin, gemcitabine and
capecitabine, plus epirubicin at 30 mg/m2 on days 1 and 15.
Treatment will be administered for a maximum of 6 cycles or until there is a clinical
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
first cycle toxicity
Dose Limiting Toxicity definition: DLT will be defined as any of the following events attributable to the administered study drugs: Hematologic toxicity Grade ≥ 4 neutropenia lasting 7 days or more Grade ≥ 3 febrile neutropenia or fever of unknown origin ≥ 38.5°C Grade 4 thrombocytopenia Grade 3 thrombocytopenia which required transfusions Nausea or vomiting Grade ≥ 3 nausea or vomiting despite maximal antiemetic therapy Diarrhea Grade ≥ 3 diarrhea despite optimal management of the event Neurological toxicity Any Grade ≥ 2 neurological toxicity Other non-hematologic toxicity Any grade ≥ 3 toxicities or representing a shift by 2 grades from baseline (in case of abnormal baseline) Failure to recover Failure to recover to grade ≤ 1 toxicity (except alopecia) or to baseline values after delaying the initiation of next cycle by > 2 weeks.
after one month from treatment start
Michele Reni, MD
IRCCS S RAFFAELE
Italy: Ministry of Health