PAXG Out in the Country

Pancreatic Ductal Adenocarcinoma Clinical Trial

— OINC  

Official title:

PAXG Out in the Country

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04480268
• Other study ID #: PACT31
• Status: Recruiting
• Phase: Phase 4
• Start date: July 8, 2020
• Est. completion date: January 1, 2026

Study information

• Verified date: February 2021
• Source: IRCCS San Raffaele
• Contact: Giulia Orsi, MD
• Phone: +390226436620
• Email: orsi.giulia[@]hsr.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 175
• Est. completion date: January 1, 2026
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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. ).

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Ductal Adenocarcinoma

Intervention

Drug:
• PAXG regimen (cisplatin, nab-paclitaxel, capecitabine, gemcitabine) chemotherapy
The PAXG regimen includes: nab-paclitaxel 150 mg/m2 on day 1 and 15 of each cycle; cisplatin 30 mg/m2 on day 1 and 15 of each cycle; capecitabine 1250 mg/m2 on 1 day to 28 of each cycle; gemcitabine 800 mg/m2 on day 1 and 15 of each cycle. Each cycle lasts 28 days. Patients are treated until maximal response, disease progression or unacceptable toxicity.

Locations

Country	Name	City	State
Italy	IRCCS Centro di Riferimento Oncologico (CRO)	Aviano
Italy	Istituto dei tumori Giovanni Paolo II	Bari
Italy	AULSS 1 di Belluno	Belluno
Italy	ASST Papa Giovanni XXIII	Bergamo
Italy	Azienda Ospedaliera Policlinico Sant'Orsola-Malpighi	Bologna
Italy	Azienda Ospedaliera AOU di Cagliari	Cagliari
Italy	Ospedale di Carpi	Carpi
Italy	USL Toscana Nord Ovest	Carrara
Italy	Fondazione Istituto Giglio	Cefalù
Italy	Ospedaliera Sant' Anna di Como Asst Lariana	Como
Italy	Azienda Ospedaliera Universitaria Ospedali Riuniti di Foggia	Foggia
Italy	ASST Rhodense	Garbagnate
Italy	Ospedale Moriggia Pelascini	Gravedona
Italy	Ospedale Generale Provinciale di Macerata	Macerata
Italy	Irccs Irst	Meldola
Italy	ASST Melegnano e Della Martesana	Melegnano
Italy	IRCCS San Raffaele Medical Oncology Unit	Milan
Italy	Istituto Oncologico Veneto IRCCS	Padova
Italy	Ospedale Civico di Palermo	Palermo
Italy	Azienda Ospedaliera di Parma	Parma
Italy	Azienda Ospedaliera di Piacenza	Piacenza
Italy	Giovanni Paolo II-Maria Paternò	Ragusa
Italy	Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi D'Aragona	Salerno
Italy	AULSS 4 Veneto Orientale	San Donà Di Piave
Italy	IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo
Italy	Azienda Ospedaliera Ordine Mauriziano	Torino
Italy	Presidio Ospedaliero Molinette	Torino
Italy	Azienda Sanitaria Universitaria Integrata	Udine
Italy	ASST Sette Laghi	Varese
Italy	Ospedale San Bortolo Azienda ULSS8 Berica-Distretto Est	Vicenza

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS San Raffaele

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival at 1 year (PFS-1yr)	Primary aim of the study is to evaluate the proportion of patients alive after 1 year from registration	12 months after the diagnosis
Secondary	Biochemical Response	To evaluate the CA19-9 response rate	12 months after the diagnosis
Secondary	Radiological Response	To evaluate the RECIST radiological response	12 months after the diagnosis
Secondary	Toxicity profile	To evaluate drugs toxicity and safety according to according to the "Common Toxicity Criteria" defined by NCI (US) and integrated by NCIC (Canada) version 5.0	12 months after the diagnosis
Secondary	Progression-free survival (PFS)	To evaluate the progression-free survival (PFS), defined as the time between the date of registration and the date of documented radiological PD or death from any cause, whichever occurs first, or the date of last follow-up or last available tumour assessment if no further follow-up for disease progression is performed.	5 year after the diagnosis
Secondary	Overall Survival (OS)	To evaluate the overall survival (OS), defined as time between the date of registration and the date of death for any cause or the date they were last known to be alive.	5 year after the diagnosis