Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Gemcitabine

Capecitabine

Albumin-Bound Paclitaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

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.

PAXG regimen (cisplatin, nab-paclitaxel, capecitabine, gemcitabine) chemotherapy

Giulia Orsi, MD

Maria Maddalena Valente, PhD

Angela Buonadonna, MD

Nicola Silvestris, MD

Fable Zustovich, MD

Barbara Merelli, MD

Maria Cristina Di Marco, MD, PhD

Mario Scartozzi, MD

Ilaria Bernardini, MD

Andrea Mambrini, MD

Massimiliano Spada, MD

Monica Giordano, MD

Matteo Landriscina, MD, PhD

Silvia Della Torre, MD

Giuseppe Valmadre, MD

Luca Faloppi, MD, PhD

Giovanni Luca Frassineti, MD

Andrea De Monte, MD

Michele Reni, MD

Sara Lonardi, MD

Livio Blasi, MD

Ingrid Garajova, MD, PhD

Luigi Cavanna, MD

Stefano Cordio, MD

Clementina Savastano, MD

Silvia Zanon, MD

Evaristo Maiello, MD

Massimo Di Maio, MD

Maria Antonietta Satolli, MD, PhD

Giovanni Gerardo Cardellino, MD

Stefania Gobba, MD

Giuseppe Aprile, MD

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.

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.

PAXG Out in the Country

Primary aim of the study is to evaluate the proportion of patients alive after 1 year from registration

To evaluate the RECIST radiological response

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

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.

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.

IRCCS San Raffaele

Micronutrients

Hematinics

Vitamins

Oxaliplatin

Leucovorin

Fluorouracil

Irinotecan

Levoleucovorin

Folic Acid

Folinic Acid

Folate

Vitamin B9

cisplatin 30 mg/m2 every 2 weeks, nab-paclitaxel 150 mg/m2 every 2 weeks, gemcitabine 800 mg/m2 every 2 weeks, capecitabine 1250 mg/m2/day (for 28 consecutive days) in 28-day cycles administered for 4 cycles (4 months).

irinotecan 150 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, folinic acid at a fixed dose of 400 mg/m2, fluorouracil continuous IV infusion 2.4 g/m2 over 46 hours in 14-day cycles administered for 8 cycles (4 months).

Allocated by second randomization after 4 months of chemotherapy to receive immediate surgery followed by 2 further months of the same chemotherapy

Allocated by second randomization after 4 months of chemotherapy to receive 2 further months of the same chemotherapy followed by surgery

Nab-paclitaxel, cisplatin and gemcitabine drugs will be administered on day 1 and 15 every 28 days. Capecitabine tablets will be taken orally on days 1 to 28, every 28 days

PAXG

Oxaliplatin, folinic acid, irinotecan and 5-Fluoruracil will be administered on day 1 and 15 every 28 days

mFOLFIRINOX

other two months of chemotherapy after surgery

short-course chemotherapy

other two months of chemotherapy before surgery

long-course chemotherapy

Claudio Bellulo, MD

Michele Simone, MD

Oronzo Brunetti, MD

Antonella Argentiero, MD

Michele Colledan, MD

Mariacristina Di Marco, MD

Riccardo Casadei, MD

Alberto Zaniboni, MD

Moh'd Abu Hilal, MD

Elisa Giommoni, MD

Lorenzo Antonuzzo, MD

Coratti Andrea, MD

Luca Faloppi, MD

Walter Siquini, MD

Luca Frassineti, MD

Silvia Bozzarelli, MD

Alessandro Zerbi, MD

Katia Bencardino, MD

Giovanni Ferrari, MD

Adolfo Pisanu, MD

Roberto Ottonello, MD

Roberto Bianco, MD

Roberto Ivan Troisi, MD

Roberto Montalti, MD

Francesca Bergamo, MD

Letizzia Procacci, MD

Valentina Palmisano, MD

Enrico Vasile, MD

Ugo Boggi, MD

Giampaolo Tortora, MD

Sergio Alfieri, MD

Alessandro Ferrero, MD

Elisa Sperti, MD

Donatella Marino, MD

Marco Massani, MD

Adolfo Favaretto, MD

Cristina Nistri, MD

Donatella Iacono, MD

Gianpiero Fasola, MD

Alessandro Uzzau, MD

Sergio Intini, MD

Claudio Bassi, MD

Michele Milella, MD

The main aim of this study is to compare the efficacy of short-course versus long-course pre-operative chemotherapy with PAXG or mFOLFIRINOX in patients who receive a diagnosis of pancreatic ductal adenocarcinoma (PDAC) resectable or borderline resectable.

Pancreatic cancer is the seventh cause of death in cancer patients and more than 94% of affected patients die of cancer disease. In the majority of cases, the diagnosis is done at an advanced stage and only 10-20% of patients can be treated with a surgical resection. For this neoplasia, a radical resection may be an effective treatment. Nevertheless, results obtained with surgery alone are rather inadequate, showing a median survival of 12-14 months and 2-year survival of almost 20%: it seems evident the necessity to use complementary treatments in order to improve survival rate in this group of patients.

Pancreatic cancer can relapse locally, at the level of tumoral bed, of the regional lymph nodes, on the immediately adjacent peritoneal surface or on contiguous organs. Also, distant metastases are quite frequent, mainly to the liver, at the entire peritoneal surface and, rarely, to the extra-abdominal organs. The rapid appearance of these metastases after surgical resection strongly suggests the presence of subclinical metastatic diffusion at an early phase of the disease.

Currently, combination chemotherapy based on the mFOLFIRINOX regimen is considered the therapeutic standard in the adjuvant setting, in young and fit patients. Unfortunately, mFOLFIRINOX is burdened with strong haematological and extra-haematologic toxicity and just 2/3 of patients are able to complete the treatment. Recently, PAXG regimen \[(Cisplatin (P), Abraxane (A), Capecitabine (X), Gemcitabine (G)\] when compared to AG in randomized studies, showed an improvement in terms of progression-free survival (PFS) and overall survival in borderline resectable, locally advanced and metastatic patients. To date, several ongoing randomized trials are investigating the efficacy of perioperative or neoadjuvant strategies in early stage PDAC. Only few studies are available regarding neoadjuvant treatment: some are outdated, numerically inconsistent, retrospective, or not randomized. In this scenario, it aims to better investigate pre-operative therapeutic strategy.

For this purpose, two randomizations are planned.

1. FIRST RANDOMIZATION. Eligible patients will be randomized (1:1), stratifying by basal CA19.9 level (\<5 ULN vs ≥ 5ULN) and centre to receive:

   PAXG or mFOLFIRINOX for 4 months
2. SECOND RANDOMIZATION. Patients without progression or limiting toxicity after 4 months of the assigned chemotherapy in the study, will be randomized (1:1), stratifying by treatment assigned by the first randomization, to receive 2 further months of the same chemotherapy either BEFORE or AFTER surgery.

Short-course Versus Long-course Pre-operative Chemotherapy With mFOLFIRINOX or PAXG (CASSANDRA TRIAL)

A Randomized Phase II Trial of Short-course Versus Long-course Pre-operative Chemotherapy With mFOLFIRINOX or PAXG Regimen for Stage I-III Pancreatic Ductal Adenocarcinoma (PDAC)

to compare in terms of event free survival (EFS) the efficacy of PAXG to that of mFOLFIRINOX. EFS is defined as the time from randomization to: RECIST 1.1 progression \[At least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20 percent, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression\]; CA19.9 failure (defined as 2 consecutive increases of serum level ≥20 percent, separated by at least 4 weeks); recurrence; preoperative or intraoperative unresectability; intraoperative evidence of metastases; death for any cause; whichever occurs first. R1 resections will NOT be considered as events whereas R2 resections will be.

to compare in terms of event free survival (EFS) the efficacy of 4 months pre-operative and 2 months postoperative chemotherapy to that of 6 months of pre-operative chemotherapy . EFS is defined as the time from randomization to: RECIST 1.1 progression \[At least a 20 percent increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20 percent, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression\]; CA19.9 failure (defined as 2 consecutive increases of serum level ≥20 percent, separated by at least 4 weeks); recurrence; preoperative or intraoperative unresectability; intraoperative evidence of metastases; death for any cause; whichever occurs first. R1 resections will NOT be considered as events whereas R2 resections will be.

the time between the date of the patient's enrollment and the death of the patient for any cause or the last time the patient was seen alive

Radiological response evaluation during the treatment by using RECIST 1.1 criteria

Biochemical response evaluation during the treatment by using this specific marker

The evaluation of surgical mortality and morbidity rate.

The evaluation of intra- and post-operative metastasis rate.

The evaluation of N0 and R0 resections rate.

The evaluation of drugs safety and tolerability by SAE report

Impact of treatment on quality of life assessed by the latest version of the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30)

Impact of treatment on quality of life assessed by the European Organization for Research and Treatment of Cancer Quality of Life scale for pancreatic cancer (EORTC QLQ - PAN26)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
PAXG Out in the Country	NCT04480268	Pancreatic Duct...	PAXG regimen (c...	18 Years - 75 Years	IRCCS San Raffaele
Short-course Versus Long-course Pre-operative Chemotherapy With mFOLFIRINOX or PAXG (CASSANDRA TRIAL)	NCT04793932	Pancreas Ductal...	PAXG mFOLFIRINOX short-course ch... long-course che...	18 Years - 75 Years	Associazione Italiana per lo Studio del Pancreas

Spots Global Cancer Trial Database for paxg

Every month we try and update this database with for paxg cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for paxg

Every month we try and update this database with for paxg cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for paxg cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.