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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Associazione Italiana Per Lo Studio Del Pancreas

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Decision date (initial)

2024-11-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519031-42-00

EudraCT number

2020-003080-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

to compare in terms of EFS the efficacy of PAXG to that of mFOLFIRINOX

Secondary objectives 1

1. to compare in terms of EFS the efficacy of 4 months pre-operative and 2 months postoperative chemotherapy to that of 6 months of pre-operative chemotherapy

Conditions and MedDRA coding

pancreatic ductal adenocarcinoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Cyto/histological diagnosis of pancreatic ductal adenocarcinoma
2. Clinical stage I-III disease according to TNM 8th Ed. 2017 [appendix 1];
3. 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)
4. Karnofsky Performance Status > 60%
5. Age  18 and ≤ 75 years
6. Adequate bone marrow function (GB ≥ 3500/mm3, neutrophils ≥1500/mm3, platelets ≥ 100000/mm3, Hb ≥10 g/dl);
7. Adequate kidney function (serum creatinine < 1.5 mg/dL);
8. Adequate liver function: - ALT and AST < 3 ULN - Serum total bilirubin ≤ 1.5 ULN or in subjects with biliary stenting ≤ 2 ULN
9. No prior treatment (chemotherapy, radiotherapy and/or surgery) for pancreatic cancer
10. Women must not be on pregnancy or lactation;
11. 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];
12. Patient information and signed written informed consent

Exclusion criteria 17

1. Other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cystadenocarcinoma and other periampullary malignancies
2. 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
3. Symptomatic duodenal stenosis
4. 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
5. 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
6. Clinical stage IV (including ascites or malignant pleural effusion) disease according to TNM 8th Ed. 2017 [appendix 1];
7. Locally advanced disease according to NCCN Guidelines Version 1.2020 – Pancreatic Adenocarcinoma [appendix 2];
8. 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: a. History of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa) b. History of interstitial lung disease, slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies c. 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
9. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
10. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
11. Any condition that confounds the ability to interpret data from the study
12. Any familiar, sociologic or geographic conditions that can potentially interfere with the adhesion to the protocol or to the follow-up;
13. Pre-existing neuropathy
14. 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.)
15. Inflammatory disease of the colon or rectum, or occlusion or sub-occlusion of the intestine
16. Concurrent treatment with other experimental drugs
17. Fructose intolerance.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. EFS, defined as the time from randomization to: RECIST 1.1 progression [At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study

Secondary endpoints 10

1. OS
2. RECIST 1.1 response rate
3. CA19.9 response rate
4. complete pathologic response
5. resectability rate
6. surgical mortality and morbidity rate
7. intra- and post-operative metastasis rate
8. N0 and R0 resections rate
9. patients reported outcomes
10. treatment toxicity

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Associazione Italiana Per Lo Studio Del Pancreas

Sponsor organisation

Associazione Italiana Per Lo Studio Del Pancreas

Address

Corso Di Francia 197

City

Rome

Postcode

00191

Country

Italy

Scientific contact point

Organisation

Associazione Italiana Per Lo Studio Del Pancreas

Contact name

Michele Reni

Public contact point

Organisation

Associazione Italiana Per Lo Studio Del Pancreas

Contact name

Michele Reni

Locations

1 EU/EEA country · 26 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications