An observational study in Metastatic Pancreatic Ductal Adenocarcinoma (PDAC), sponsored by Hellenic Cooperative Oncology Group. Recruiting at 9 sites in Greece. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-24.
Sponsored by Hellenic Cooperative Oncology Group · Observational
This is multicenter, prospective, open label, non-interventional study that will collect real-world data (RWD) on the clinical efficacy and safety of NalIriFOx as a first-line therapy in metastatic pancreatic ductal adenocarcinoma (mPDAC).
Pancreatic cancer is an aggressive malignancy with a dismal prognosis, often diagnosed at an advanced stage where curative treatment options are limited. It is the seventh leading cause of cancer-related deaths globally, with a five-year survival rate of less than 10%.
Progress with systemic therapy for patients with advanced pancreatic cancer has historically been slow. However, therapeutic advances in the past 12 years have resulted in modest yet tangible improvements for patients.
Current first-line treatment options for metastatic pancreatic cancer include combination chemotherapy regimens such as FOLFIRINOX (a combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel.
FOLFIRINOX has demonstrated significant improvements in overall survival and progression-free survival compared to gemcitabine alone, albeit with increased toxicity. Although FOLFIRINOX has achieved longer median OS compared to gemcitabine - nab-Paclitaxel, its poor toxicity profile made its use very difficult in clinical practice. Therefore, FOLFIRINOX has practically been substituted by the better tolerated modified FOLFIRINOX which has not been formally tested in a randomized clinical trial. Therefore, it remains a need for more effective and better-tolerated first-line therapies for metastatic pancreatic cancer patients.
Liposomal irinotecan or nal-IRI, also known as pegylated liposomal irinotecan and abbreviated as MM-398 or PEP02, has emerged as the only registered post-gemcitabine treatment in mPDAC, often used in the second line after a gemcitabine-based first -line regimen. Nal-IRI is an intravenous liposomal formulation that encapsulates the topoisomerase I inhibitor irinotecan in a lipid-bilayer vesicle.
Nal-IRI was developed to overcome the pharmacological and clinical shortcomings of the conventional formulation of the drug, aiming to maximize antitumor efficacy while minimizing treatment-related toxicities. Results from the NAPOLI-1 study (NCT01494506) demonstrated the survival benefit of nal-IRI plus 5-FU/LV following disease progression with gemcitabine-based therapy in patients with mPDAC.
The combination therapy of nal-IRI + 5-FU/LV significantly increased the median overall survival (OS: 6.1 months, 95% confidence interval [CI]: 4.8-8.9) and progression-free survival (PFS) (3.1 months, 95% CI: 2.7-4.2) as compared with 5-FU/LV alone (OS: 4.2 months, 95% CI: 3.3-5.3; PFS: 1.5 months, 95% CI: 1.4-1.8). It was confirmed in an updated analysis published in 2019.
Moreover, in a phase 1/2 trial (NCT02551991), liposomal irinotecan, in combination with fluorouracil, leucovorin, and oxaliplatin (NALIRIFOX), demonstrated promising antitumor activity in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma.
The NALIRIFOX regimen, comprising nanoliposomal irinotecan, fluorouracil, leucovorin, and oxaliplatin, has emerged as a promising alternative to traditional FOLFIRINOX.
Considering the efficacy of FOLFIRINOX and the improved properties of nanoliposomal irinotecan, the NALIRIFOX regimen holds the potential to provide a more potent and well-tolerated first-line treatment option.
The results of the Phase 3 Study NAPOLI 3 were very prominent. The rationale of the NAPOLI 3 study was to evaluate the efficacy and safety of the NALIRIFOX regimen in patients metastatic pancreatic cancer who have not received prior treatment for metastatic disease, aiming to improve survival outcomes and quality of life for this patient population.
Median overall survival was 11·1 months (95% CI 10·0-12·1) with NALIRIFOX versus 9·2 months (8·3-10·6) with nab-paclitaxel-gemcitabine (hazard ratio 0·83; 95% CI 0·70-0·99; p=0·036). Grade 3 or higher treatment-emergent adverse events occurred in 322 (87%) of 370 patients receiving NALIRIFOX and 326 (86%) of 379 patients receiving nab-paclitaxel-gemcitabine; treatment-related deaths occurred in six (2%) patients in the NALIRIFOX group and eight (2%) patients in the nabpaclitaxel-gemcitabine group.
The data from the clinical trial NAPOLI 3 justify using the combination of NalIriFOx as a first-line therapy in mPDAC. Although randomized controlled trials (RCTs) are crucial in assessing drug efficacy and safety, the generated data are often different from those obtained in daily clinical practice.
By leveraging real-world data, this study aims to provide comprehensive insights into the regimen's clinical performance, patient outcomes, and tolerability in routine clinical practice, thereby informing and optimizing treatment strategies for this challenging disease.
Real-world data (RWD) and real-world evidence (RWE) play a crucial role in understanding the performance of new therapies in diverse patient populations outside the controlled environment of clinical trials. RWD can reveal variations in treatment responses, identify rare adverse events, and offer insights into patient quality of life and healthcare resource utilization.
This RWE study will thus contribute valuable information on the applicability and benefits of the NALIRIFOX regimen in a real-world setting, aligning clinical efficacy with practical utility.
This is multicenter, prospective, open label, non-interventional study that will collect real-world data (RWD) on the clinical efficacy and safety of NalIriFOx as a first-line therapy in metastatic pancreatic ductal adenocarcinoma (mPDAC).
NaLIriFOX falls within the current practice as first-line treatment in patients with metastatic ductal adenocarcinoma. No additional diagnostic or monitoring procedures will be applied to the patients participating in this study.
Hellenic Cooperative Oncology Group is the lead sponsor of 62 studies on the registry; 6 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients with mPDAC receiving NalIriFOx as first line therapy
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
mPDAC patients receiving NalIriFox as a first line therapy
Real World Data collection
Record clinical practice and collect real-world data (RWD) on the clinical efficacy and safety of NalIriFOx as a first-line therapy in mPDAC
Time frame: Time from study entry untill completion (12 months)
Progression Free Survival (PFS)
PFS of mPDAC patients after first line treatment with NalIriFOx
Time frame: Time from study entry to first recurrence (local, regional, distant) or death from any cause, whichever comes first, assessed up to 12 months]
Overall Survival (OS)
To investigate the long-term prognostic significance of mPDAC patients receiving NalIriFOx as first line therapy, in terms of OS
Time frame: Time from study entry to death from any cause, assessed up to 12 months
Plan to share: Undecided
No publications or documents are linked to this record.
Started Mar 2026 (actual). Primary completion is estimated for Mar 2029, 36 months after the start.
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Hellenic Cooperative Oncology Group