Hellenic Evaluation of the Long-Term Safety and Efficacy of NalIriFOx as a 1st-line Therapy in Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) (HELIOS)

July 23, 2026 updated by: Hellenic Cooperative Oncology Group
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).

Study Overview

Status

Recruiting

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

70

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Greece
      • Athens, Greece, 151 23
        • Recruiting
        • Hygeia Hospital
        • Contact:
      • Athens, Greece, 124 62
        • Recruiting
        • Attikon University General Hospital
        • Contact:
      • Athens, Greece, 145 64
        • Recruiting
        • General Oncology Hospital Agioi Anargyroi
        • Contact:
      • Athens, Greece, 185 47
        • Recruiting
        • 2nd Oncology Department, Metropolitan Hospital
        • Contact:
      • Athens, Greece
      • Larissa, Greece
        • Recruiting
        • Larissa University General Hospital
        • Contact:
      • Pátrai, Greece, 263 32
        • Recruiting
        • General Hospital Agios Andreas
        • Contact:
      • Thessaloniki, Greece, 570 10
        • Recruiting
        • Thessaloniki General Hospital "George Papanikolaou"
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with mPDAC receiving NalIriFOx as first line therapy

Description

Inclusion Criteria:

  • Patients with histologically or cytologically proven metastatic PDAC
  • 1st line treatment with NalIriFOx according to physician's choice
  • Patients willing to provide a Written Informed Consent

Exclusion Criteria:

  • Patients not matching the above-mentioned inclusion criteria
  • Neoadjuvant or adjuvant treatment within 6 months from enrolment
  • Prior treatment with Liposomal irinotecan
  • Prior treatment of pancreatic cancer in the metastatic setting with chemotherapy or investigational therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
mPDAC patients
mPDAC patients receiving NalIriFox as a first line therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Real World Data collection
Time Frame: Time from study entry untill completion (12 months)
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 from study entry untill completion (12 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
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]
PFS of mPDAC patients after first line treatment with NalIriFOx
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)
Time Frame: Time from study entry to death from any cause, assessed up to 12 months
To investigate the long-term prognostic significance of mPDAC patients receiving NalIriFOx as first line therapy, in terms of OS
Time from study entry to death from any cause, assessed up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hellenic Cooperative Oncology Group

Investigators

  • Principal Investigator: Athina Christopoulou, MD, PhD, Oncology Unit, General Hospital of Patras "Agios Andreas"
  • Principal Investigator: George Papaxoinis, MD, 2nd Dept of Medical Oncology, "Agios Savvas" Anti Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 30, 2026

Primary Completion (Estimated)

March 30, 2029

Study Completion (Estimated)

March 30, 2029

Study Registration Dates

First Submitted

July 20, 2026

First Submitted That Met QC Criteria

July 20, 2026

First Posted (Actual)

July 23, 2026

Study Record Updates

Last Update Posted (Actual)

July 24, 2026

Last Update Submitted That Met QC Criteria

July 23, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • HE3/24

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Brazil

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe