Clinical trial NCT04480268: PAXG Out in the Country
Official title: PAXG Out in the Country
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Pancreatic Ductal Adenocarcinoma
Keywords: Combination chemotherapy
PAXG
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2020-07-21
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to assess the reproducibility of PAXG regimen as first-line/primary chemotherapy in daily clinical practice in Pancreatic Ductal Adenocarcinoma (PDAC) borderline resectable, locally advanced or metastatic patients out of a large volume center.

Detailed description: Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal malignancies, with a 5-year overall survival (OS) rate for all stages combined lower than 10%, decreasing to 3% in advanced disease. Additionally, PDAC is expected to become the 2nd leading cause for cancer-related death by 2030. Chemotherapy still represents the only therapeutic option in most cases, since 70% of PDAC patients exhibit metastatic or locally advanced disease at diagnosis. Concerning metastatic PDAC patients, combination chemotherapy has resulted in improved survival compared with single-agent treatment. Based on promising phase I/II studies, the PAXG regimen (cisplatin, nab-paclitaxel, capecitabine and gemcitabine) has been recommended for first-line treatment of metastatic PDAC patients in the 2019 edition of Associazione Italiana Oncologia Medica (AIOM) guidelines. Also, this regimen was approved by the Agenzia Italiana del Farmaco (AIFA) as first therapy of borderline-resectable, locally advanced and metastatic PDAC patients with good performance status (ECOG 0-1) and age 18-75 years.

Description of the intervention (schedule of visits):

All PDAC patients who are treated with PAXG regimen as first-line/primary chemotherapy at the participating institutions from January 1st 2020 to December 31st 2020 according to inclusion and exclusion criteria will be included in the present study.

Power size calculation:

The sample size will be as large as possible with a competitive enrollment. All patients treated by the PAXG regimen during 2020 in the participating institutions will be included into the trial. The investigators hypothesize that at least 175 patients (60% metastatic and 40% non-metastatic) from about 30 Italian centers will be enrolled by the end of the year. Such a sample size, or a larger one, will allow to compute in both groups a 95% confident interval of the 1-year OS with at least 10% margin of error, assuming to observe a (target) 1-year OS of 60% for metastatic patients and of 80% for non-metastatic. The trial will be considered successful if the target 1-year OS will fall into the corresponding computed 95% CI.

Eligibility criteria: Inclusion Criteria:

* cyto/histological diagnosis of pancreatic adenocarcinoma;
* locally advanced and metastatic disease corresponding to clinical stage III-IV according to TNM 8th Ed. 2017 and borderline resectable disease as anatomically defined according to NCCN Guidelines Version 1.2020 - Pancreatic Adenocarcinoma and biologically defined according to the International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017 (CA 19.9 \> 500 IU/ml);
* ECOG Performance Status ≤1;
* adequate bone marrow function (GB ≥ 3500/mm3, neutrophils ≥1500/mm3, platelets ≥ 100000/mm3, Hb ≥10 g/dl), kidney function (serum creatinine \< 1.5 mg/dL) and liver function (ALT and AST \< 3 ULN and Serum total bilirubin ≤ 1.5 ULN);
* Patient of child-bearing potential must agree to use two medically acceptable methods of contraception (one for the patient and one for the partner) during the study and for 4 months after the last study treatment intake for women and 6 months for men;
* patients must have received at least 1 cycle (28 days) of the PAXG treatment for the disease within the timeframe starting from January 1 2020 to December 31st 2020 ;
* patient information and signed written informed consent.

Exclusion Criteria:

* previous chemotherapy treatment for recurrent disease;
* concurrent treatment with experimental drugs;
* presence of symptomatic brain metastases;
* heart failure, arrhythmia and/or acute myocardial infarction within 6 months prior to the beginning of PAXG treatment;
* women on pregnancy or lactation;
* history of interstitial lung disease;
* history of connective tissue diseases (systemic lupus erythematosus, systemic sclerosis, etc. ).

Primary outcomes:
measure: Progression-free survival at 1 year (PFS-1yr)
timeFrame: 12 months after the diagnosis
Secondary outcomes:
measure: Biochemical Response
timeFrame: 12 months after the diagnosis
measure: Radiological Response
timeFrame: 12 months after the diagnosis
measure: Toxicity profile
timeFrame: 12 months after the diagnosis
measure: Progression-free survival (PFS)
timeFrame: 5 year after the diagnosis
measure: Overall Survival (OS)
timeFrame: 5 year after the diagnosis
Other outcomes:
Locations:
city: Aviano
country: Italy
facility: IRCCS Centro di Riferimento Oncologico (CRO)
city: Bari
country: Italy
facility: Istituto dei tumori Giovanni Paolo II
city: Belluno
country: Italy
facility: AULSS 1 di Belluno
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Azienda Ospedaliera Policlinico Sant'Orsola-Malpighi
city: Cagliari
country: Italy
facility: Azienda Ospedaliera AOU di Cagliari
city: Carpi
country: Italy
facility: Ospedale di Carpi
city: Carrara
country: Italy
facility: USL Toscana Nord Ovest
city: Cefalù
country: Italy
facility: Fondazione Istituto Giglio
city: Como
country: Italy
facility: Ospedaliera Sant' Anna di Como Asst Lariana
city: Foggia
country: Italy
facility: Azienda Ospedaliera Universitaria Ospedali Riuniti di Foggia
city: Garbagnate
country: Italy
facility: ASST Rhodense
city: Gravedona
country: Italy
facility: Ospedale Moriggia Pelascini
city: Macerata
country: Italy
facility: Ospedale Generale Provinciale di Macerata
city: Meldola
country: Italy
facility: Irccs Irst
city: Melegnano
country: Italy
facility: ASST Melegnano e Della Martesana
city: Milan
country: Italy
facility: IRCCS San Raffaele Medical Oncology Unit
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS
city: Palermo
country: Italy
facility: Ospedale Civico di Palermo
city: Parma
country: Italy
facility: Azienda Ospedaliera di Parma
city: Piacenza
country: Italy
facility: Azienda Ospedaliera di Piacenza
city: Ragusa
country: Italy
facility: Giovanni Paolo II-Maria Paternò
city: Salerno
country: Italy
facility: Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi D'Aragona
city: San Donà Di Piave
country: Italy
facility: AULSS 4 Veneto Orientale
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Casa Sollievo della Sofferenza
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano
city: Torino
country: Italy
facility: Presidio Ospedaliero Molinette
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata
city: Varese
country: Italy
facility: ASST Sette Laghi
city: Vicenza
country: Italy
facility: Ospedale San Bortolo Azienda ULSS8 Berica-Distretto Est
Study officials:
affiliation: IRCCS Ospedale San Raffaele
name: Michele Reni, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reni M, Cereda S, Rognone A, Belli C, Ghidini M, Longoni S, Fugazza C, Rezzonico S, Passoni P, Slim N, Balzano G, Nicoletti R, Cappio S, Doglioni C, Villa E. A randomized phase II trial of two different 4-drug combinations in advanced pancreatic adenocarcinoma: cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel (PEXG or PDXG regimen). Cancer Chemother Pharmacol. 2012 Jan;69(1):115-23. doi: 10.1007/s00280-011-1680-2. Epub 2011 May 28.
citation: Reni M, Balzano G, Zanon S, Passoni P, Nicoletti R, Arcidiacono PG, Pepe G, Doglioni C, Fugazza C, Ceraulo D, Falconi M, Gianni L. Phase 1B trial of Nab-paclitaxel plus gemcitabine, capecitabine, and cisplatin (PAXG regimen) in patients with unresectable or borderline resectable pancreatic adenocarcinoma. Br J Cancer. 2016 Jul 26;115(3):290-6. doi: 10.1038/bjc.2016.209. Epub 2016 Jul 12.
citation: Reni M, Zanon S, Peretti U, Chiaravalli M, Barone D, Pircher C, Balzano G, Macchini M, Romi S, Gritti E, Mazza E, Nicoletti R, Doglioni C, Falconi M, Gianni L. Nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in metastatic pancreatic adenocarcinoma (PACT-19): a randomised phase 2 trial. Lancet Gastroenterol Hepatol. 2018 Oct;3(10):691-697. doi: 10.1016/S2468-1253(18)30196-1. Epub 2018 Jul 7.
citation: Reni M, Zanon S, Balzano G, Passoni P, Pircher C, Chiaravalli M, Fugazza C, Ceraulo D, Nicoletti R, Arcidiacono PG, Macchini M, Peretti U, Castoldi R, Doglioni C, Falconi M, Partelli S, Gianni L. A randomised phase 2 trial of nab-paclitaxel plus gemcitabine with or without capecitabine and cisplatin in locally advanced or borderline resectable pancreatic adenocarcinoma. Eur J Cancer. 2018 Oct;102:95-102. doi: 10.1016/j.ejca.2018.07.007. Epub 2018 Aug 24.