Pancreas Ductal AdenocarcinomaPhase 3CASSANDRANCT04793932

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

A Phase 3 study testing PAXG, mFOLFIRINOX and short-course chemotherapy in people with Pancreas Ductal Adenocarcinoma, run by Associazione Italiana per lo Studio del Pancreas at 22 sites in Italy.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Pancreas Ductal Adenocarcinoma
What is being tested?: PAXG, mFOLFIRINOX and short-course chemotherapy
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 261 participants
Where: 22 sitesItaly
Study dates: 3 Nov 2020to 31 Jan 2026
Phase: Phase 3
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Cyto/histological diagnosis of pancreatic ductal adenocarcinoma*;
Clinical stage I-III disease according to TNM 8th Ed. 2017 [appendix 1];
Resectable or borderline resectable disease, as anatomically defined according to NCCN Guidelines Version 1.2020 - Pancreatic Adenocarcinoma [appendix 2] 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) (Isaji et al., 2018);
Karnofsky Performance Status > 60% [appendix 3];
Age > 18 and ≤ 75 years;
Adequate bone marrow function (GB ≥ 3500/mm3, neutrophils ≥1500/mm3, platelets ≥ 100000/mm3, Hb ≥10 g/dl);

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Adequate kidney function (serum creatinine < 1.5 mg/dL);
Adequate liver function:
ALT and AST < 3 ULN
Serum total bilirubin ≤ 1.5 ULN or in subjects with biliary stenting ≤ 2 ULN;
No prior treatment (chemotherapy, radiotherapy and/or surgery) for pancreatic cancer;
Women must not be on pregnancy or lactation;
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 a minimum of the following 6 months; this applies to patients of both sexes. [appendix 4];
Patient information and signed written informed consent.

Who cannot join

Other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cystadenocarcinoma and other periampullary malignancies.
Prior (within 1 year) or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin
Symptomatic duodenal stenosis;
Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment
Known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications
Clinical stage IV (including ascites or malignant pleural effusion) disease according to TNM 8th Ed. 2017 [appendix 1];

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Locally advanced disease according to NCCN Guidelines Version 1.2020 - Pancreatic Adenocarcinoma [appendix 2];
Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders, which could compromise the subject's safety or the study data integrity. These include, but are not limited to:
History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa)
History of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies
History of the following within 6 months prior to Cycle 1 Day 1: a myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) Class III-IV heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or ECG abnormality, cerebrovascular accident, transient ischemic attack, or seizure disorder
Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
Any condition that confounds the ability to interpret data from the study
Any familiar, sociologic or geographic conditions that can potentially interfere with the adhesion to the protocol or to the follow-up;
Pre-existing neuropathy
c.1679GG, c.1905+1AA, c.2846TT mutations in homozygous in DPYD gene. Dose modification according to DPYD and UGT1A1 mutations are reported in Table 1 (https://www.aiom.it/wp-content/uploads/2019/10/2019_Racc-analisi-farmacogenetiche.pdf.)
Inflammatory disease of the colon or rectum, or occlusion or sub-occlusion of the intestine.
Concurrent treatment with other experimental drugs;
Fructose intolerance.

Trial locations and contacts

22 sites in 1 country.

City, postcode or hospital

22 sites in 1 country

Italy22 sites

Oncologia Medica e Prevenzione Oncologica Centro di riferimento oncologico (CRO), IRCCS
Aviano, 33081
Oncologia Medica Az. Ospedaliera Istituto Tumori "Giovanni Paolo II"
Bari, 70124
Oncologia ASST pg23
Bergamo, 24127
Oncologia Medica Azienda Universitaria Ospedaliera Policlinico Sant'Orsola-Malpighi
Bologna, 40138
Oncologia Medica dell'Az.Ospedaliera Fondazione Poliambulanza Istituto Ospedaliero
Brescia, 25124
Oncologia Medica AOU Careggi
Florence, 50134
Oncologia Medica dell'Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, 47014
Oncologia dell'Istituto Clinico Humanitas
Milan, 20089
IRCCS San Raffaele
Milan, 20132
Oncologia Medica Falck Niguarda
Milan, 20162
Oncologia Medica Az Ospedaliera AOU Cagliari Policlinico Universitario Dullio Casula
Monserrato, 09042
Oncologia Medica AOU FEDERICO II
Naples, 80131
Oncologia Medica 1 Ospedaliera Istituto Oncologico Veneto IRCCS
Padova, 35128
Oncologia Medica Arnas Civico
Palermo, 90121
Oncologia Medica 2 Az. Ospedaliera Universitaria Pisana
Pisa, 56126
Oncologia Ospedale Generale Provinciale
Province of Macerata, 62100
Oncologia Medica Az. Ospedaliera Fondazione Policlinico Universitario A. Gemelli IRCCS
Rome, 00168
Chirurgia Generale e Oncologica dell'AZ. Ospedaliera Ordine Mauriziano
Torino, 10028
Divisione Chirurgica Az. Ospedaliera AULSS2
Treviso, 31100
SOC di Oncologia Az. Ospedaliera Sanitaria Universitaria Friuli Centrale-P.O. "S. Maria della Misericordia"
Udine, 33100
Chirurgia generale e del Pancreas Azienda Ospedaliera Universitaria Integrata
Verona, 37136
Oncologia ULSS8 Berica
Vicenza, 36100

Other trials in Italy

About this study

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

Read the detailed description

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.

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
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.

Conditions: Pancreas Ductal Adenocarcinoma
Being tested: PAXG, mFOLFIRINOX, short-course chemotherapy, long-course chemotherapy
Keywords: neoadjuvant chemotherapy, PAXG, mFOLFIRINOX, resectable, borderline resectable

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PAXGDrug
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
mFOLFIRINOXDrug
Oxaliplatin, folinic acid, irinotecan and 5-Fluoruracil will be administered on day 1 and 15 every 28 days
short-course chemotherapyDrug
other two months of chemotherapy after surgery
long-course chemotherapyDrug
other two months of chemotherapy before surgery

Study groups in NCT04793932
Study group	Role	What they receive
PAXG Arm A	Active comparator	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). Receives: Drug: PAXG
mFOLFIRINOX Arm B	Active comparator	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). Receives: Drug: mFOLFIRINOX
short-course chemotherapy	Active comparator	Allocated by second randomization after 4 months of chemotherapy to receive immediate surgery followed by 2 further months of the same chemotherapy Receives: Drug: short-course chemotherapy
long-course chemotherapy	Active comparator	Allocated by second randomization after 4 months of chemotherapy to receive 2 further months of the same chemotherapy followed by surgery Receives: Drug: long-course chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

Event-free survival
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.
Measured: 12 weeks
Event-free survival
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.
Measured: 12 weeks

Secondary outcomes (10)

Overall survival
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
Measured: 36 months
RECIST 1.1 radiological response
Radiological response evaluation during the treatment by using RECIST 1.1 criteria
Measured: 4-6 months
Ca19.9 response rate
Biochemical response evaluation during the treatment by using this specific marker
Measured: 4-6 months
Surgery outcome
The evaluation of resectability rate.
Measured: 4-6 months after chemotherapy
Surgery outcome
The evaluation of surgical mortality and morbidity rate.
Measured: 4-6 months after chemotherapy
Surgery outcome
The evaluation of intra- and post-operative metastasis rate.
Measured: 4-6 months after chemotherapy
Surgery outcome
The evaluation of N0 and R0 resections rate.
Measured: 4-6 months after chemotherapy
Incidence of Treatment Adverse Events
The evaluation of drugs safety and tolerability by SAE report
Measured: 4-6 months
Quality of life
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)
Measured: 4-6 months
Quality of life
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)
Measured: 4-6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Nov 202031 Jan 2026

First posted11 Mar 2021
Study start3 Nov 2020
Primary completion15 Mar 2025
Study completion31 Jan 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Pancreas Ductal AdenocarcinomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Model description: 2 by 2
Masking: None (open label)
Enrolment: 261 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04793932
Sponsor's protocol ID: PACT21
Acronym: CASSANDRA
Status last verified: Mar 2025
First submitted: 28 Feb 2021
Last updated: 9 Apr 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Reni M, Cereda S, Mazza E, Passoni P, Nicoletti R, Balzano G, Zerbi A, Arcidiacono PG, Staudacher C, Di Carlo V. PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) regimen as second-line therapy in patients with progressive or recurrent pancreatic cancer after gemcitabine-containing chemotherapy. Am J Clin Oncol. 2008 Apr;31(2):145-50. doi: 10.1097/COC.0b013e31814688f7.
PubMed 18391598
Reni M, Balzano G, Aprile G, Cereda S, Passoni P, Zerbi A, Tronconi MC, Milandri C, Saletti P, Rognone A, Fugazza C, Magli A, Di Muzio N, Di Carlo V, Villa E. Adjuvant PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) or gemcitabine followed by chemoradiation in pancreatic cancer: a randomized phase II trial. Ann Surg Oncol. 2012 Jul;19(7):2256-63. doi: 10.1245/s10434-011-2205-2. Epub 2012 Jan 12.
PubMed 22237835
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.
PubMed 27404453
Reni M, Balzano G, Zanon S, Zerbi A, Rimassa L, Castoldi R, Pinelli D, Mosconi S, Doglioni C, Chiaravalli M, Pircher C, Arcidiacono PG, Torri V, Maggiora P, Ceraulo D, Falconi M, Gianni L. Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial. Lancet Gastroenterol Hepatol. 2018 Jun;3(6):413-423. doi: 10.1016/S2468-1253(18)30081-5. Epub 2018 Apr 4.
PubMed 29625841
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.
PubMed 30149366
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.
PubMed 30220407
Reni M, Orsi G, Carconi C, Malleo G, Procaccio L, Macchini M, Bencardino K, Merelli B, Pretta A, Rapposelli IG, Pecorelli N, Partelli S, Sperti E, Crippa S, Liscia N, Di Marco M, Milella M, Lonardi S, Palumbo D, Torri V, Falconi M. Short-term versus long-course neoadjuvant chemotherapy for resectable and borderline resectable pancreatic ductal adenocarcinoma (PACT-21 CASSANDRA): results from the second randomisation analysis of a randomised, open-label, 2 x 2 factorial phase 3 trial. EClinicalMedicine. 2026 Sep 5;99:104190. doi: 10.1016/j.eclinm.2026.104190. eCollection 2026 Sep.
PubMed 42733563
Reni M, Macchini M, Orsi G, Procaccio L, Malleo G, Carconi C, Rapposelli IG, Bencardino K, Scartozzi M, Balzano G, Tamburrino D, Merelli B, Sperti E, Belfiori G, Liscia N, Bozzarelli S, Di Marco M, Tamburini E, Milella M, Lonardi S, Ercolani G, Mazzola M, Palumbo D, Torri V, Falconi M. Preoperative mFOLFIRINOX versus PAXG for stage I-III resectable and borderline resectable pancreatic ductal adenocarcinoma (PACT-21 CASSANDRA): results of the first randomisation analysis of a randomised, open-label, 2 x 2 factorial phase 3 trial. Lancet. 2026 Dec 20;406(10522):2945-2956. doi: 10.1016/S0140-6736(25)01685-X. Epub 2025 Nov 20.
PubMed 41275879

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 9 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Phase III Trial of Short-course Versus Long-course Pre-operative Chemotherapy With mFOLFIRINOX or PAXG Regimen for Stage I-III Pancreatic Ductal Adenocarcinoma (PDAC)
ClinicalTrials.gov ID: NCT04793932
Acronym / sponsor ID: CASSANDRA / PACT21
Conditions: Pancreas Ductal Adenocarcinoma
Keywords: neoadjuvant chemotherapy, PAXG, mFOLFIRINOX, resectable, borderline resectable
Phase: Phase 3
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 261 participants (actual)
Lead sponsor: Associazione Italiana per lo Studio del PancreasUniversity, hospital or other
Collaborators: High Research srl, Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
Study start: 3 Nov 2020 (actual)
Primary completion: 15 Mar 2025 (actual)
Study completion: 31 Jan 2026 (estimated)
First posted: 11 Mar 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

For this purpose, two randomizations are planned.

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
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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: None (open label)
Number of arms: 4
Model description: 2 by 2

Arm	Type	Receives
PAXG Arm A	Active comparator	Drug: PAXGcisplatin 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).
mFOLFIRINOX Arm B	Active comparator	Drug: mFOLFIRINOXirinotecan 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).
short-course chemotherapy	Active comparator	Drug: short-course chemotherapyAllocated by second randomization after 4 months of chemotherapy to receive immediate surgery followed by 2 further months of the same chemotherapy
long-course chemotherapy	Active comparator	Drug: long-course chemotherapyAllocated by second randomization after 4 months of chemotherapy to receive 2 further months of the same chemotherapy followed by surgery

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Cyto/histological diagnosis of pancreatic ductal adenocarcinoma*;
Clinical stage I-III disease according to TNM 8th Ed. 2017 [appendix 1];
Resectable or borderline resectable disease, as anatomically defined according to NCCN Guidelines Version 1.2020 - Pancreatic Adenocarcinoma [appendix 2] 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) (Isaji et al., 2018);
Karnofsky Performance Status > 60% [appendix 3];
Age > 18 and ≤ 75 years;

Key exclusion criteria (20 listed)

Other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cystadenocarcinoma and other periampullary malignancies.
Prior (within 1 year) or concurrent malignancies at other sites with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin
Symptomatic duodenal stenosis;
Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment
Known infection with hepatitis B or C, or history of human immunodeficiency virus (HIV) infection, or subject receiving immunosuppressive or myelosuppressive medications that would in the opinion of the investigator, increase the risk of serious neutropenic complications

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PAXGNab-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	Drug	PAXG Arm A
mFOLFIRINOXOxaliplatin, folinic acid, irinotecan and 5-Fluoruracil will be administered on day 1 and 15 every 28 days	Drug	mFOLFIRINOX Arm B
short-course chemotherapyother two months of chemotherapy after surgery	Drug	short-course chemotherapy
long-course chemotherapyother two months of chemotherapy before surgery	Drug	long-course chemotherapy

Primary outcome

Event-free survival
Time frame: 12 weeks
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.
Event-free survival
Time frame: 12 weeks
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.

10 secondary outcomes

Overall survival
Time frame: 36 months
RECIST 1.1 radiological response
Time frame: 4-6 months
Ca19.9 response rate
Time frame: 4-6 months
Surgery outcome
Time frame: 4-6 months after chemotherapy
Surgery outcome
Time frame: 4-6 months after chemotherapy
Surgery outcome
Time frame: 4-6 months after chemotherapy
Surgery outcome
Time frame: 4-6 months after chemotherapy
Incidence of Treatment Adverse Events
Time frame: 4-6 months
Quality of life
Time frame: 4-6 months
Quality of life
Time frame: 4-6 months

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2025.
Background: PubMed 18391598Reni M, Cereda S, Mazza E, Passoni P, Nicoletti R, Balzano G, Zerbi A, Arcidiacono PG, Staudacher C, Di Carlo V. PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) regimen as second-line therapy in patients with progressive or recurrent pancreatic cancer after gemcitabine-containing chemotherapy. Am J Clin Oncol. 2008 Apr;31(2):145-50. doi: 10.1097/COC.0b013e31814688f7.
Background: PubMed 22237835Reni M, Balzano G, Aprile G, Cereda S, Passoni P, Zerbi A, Tronconi MC, Milandri C, Saletti P, Rognone A, Fugazza C, Magli A, Di Muzio N, Di Carlo V, Villa E. Adjuvant PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) or gemcitabine followed by chemoradiation in pancreatic cancer: a randomized phase II trial. Ann Surg Oncol. 2012 Jul;19(7):2256-63. doi: 10.1245/s10434-011-2205-2. Epub 2012 Jan 12.
Background: PubMed 27404453Reni 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.
Background: PubMed 29625841Reni M, Balzano G, Zanon S, Zerbi A, Rimassa L, Castoldi R, Pinelli D, Mosconi S, Doglioni C, Chiaravalli M, Pircher C, Arcidiacono PG, Torri V, Maggiora P, Ceraulo D, Falconi M, Gianni L. Safety and efficacy of preoperative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial. Lancet Gastroenterol Hepatol. 2018 Jun;3(6):413-423. doi: 10.1016/S2468-1253(18)30081-5. Epub 2018 Apr 4.
Background: PubMed 30149366Reni 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.
Background: PubMed 30220407Reni 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.
Derived from this study: PubMed 42733563Reni M, Orsi G, Carconi C, Malleo G, Procaccio L, Macchini M, Bencardino K, Merelli B, Pretta A, Rapposelli IG, Pecorelli N, Partelli S, Sperti E, Crippa S, Liscia N, Di Marco M, Milella M, Lonardi S, Palumbo D, Torri V, Falconi M. Short-term versus long-course neoadjuvant chemotherapy for resectable and borderline resectable pancreatic ductal adenocarcinoma (PACT-21 CASSANDRA): results from the second randomisation analysis of a randomised, open-label, 2 x 2 factorial phase 3 trial. EClinicalMedicine. 2026 Sep 5;99:104190. doi: 10.1016/j.eclinm.2026.104190. eCollection 2026 Sep.
Derived from this study: PubMed 41275879Reni M, Macchini M, Orsi G, Procaccio L, Malleo G, Carconi C, Rapposelli IG, Bencardino K, Scartozzi M, Balzano G, Tamburrino D, Merelli B, Sperti E, Belfiori G, Liscia N, Bozzarelli S, Di Marco M, Tamburini E, Milella M, Lonardi S, Ercolani G, Mazzola M, Palumbo D, Torri V, Falconi M. Preoperative mFOLFIRINOX versus PAXG for stage I-III resectable and borderline resectable pancreatic ductal adenocarcinoma (PACT-21 CASSANDRA): results of the first randomisation analysis of a randomised, open-label, 2 x 2 factorial phase 3 trial. Lancet. 2026 Dec 20;406(10522):2945-2956. doi: 10.1016/S0140-6736(25)01685-X. Epub 2025 Nov 20.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michele Reni, MD study chair

IRCCS San Raffaele

22 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing PAXG, mFOLFIRINOX and short-course chemotherapy in people with Pancreas Ductal Adenocarcinoma, run by Associazione Italiana per lo Studio del Pancreas at 22 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04793932, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2025.