Metastatic Pancreatic CancerPhase 2NAPANNCT03986294
Second Line Treatment With Nal-IRI and S1 in Pancreatic Cancer
A Phase 2 study testing S1 + Nal-IRI and Nal-IRI+Leucovorin+5-FU in people with Metastatic Pancreatic Cancer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
To determine the optimal second line treatment strategy in patients with metastatic pancreatic cancer who underwent a therapy with gemcitabine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Pancreatic Cancer
- What is being tested?
- S1 + Nal-IRI and Nal-IRI+Leucovorin+5-FU
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Dec 2019to 1 Jan 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must satisfy all of the following inclusion criteria to be enrolled in the study.
- Able to understand and provide written informed consent
- ≥ 18 years of age
- Histologically or cytologically confirmed adenocarcinoma of pancreas
- Documented metastatic disease, according to RECIST 1.1.
- Previously treated with gemcitabine or gemcitabine containing therapy, or progression within 6 months of adjuvant gemcitabine based treatment
- Adequate hepatic, renal and hematological function
Who cannot join
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Serum total bilirubin ≥1.5 x ULN (biliary drainage is allowed for biliary obstruction)
- Severe renal impairment (CLcr ≤ 30 ml/min)
- Inadequate bone marrow reserves as evidenced by:
- ANC ≤ 1,5 x 10 9 /L; or
- Platelet count ≤ 100 x 10 9 /L;
Show all 19Show fewer
- WHO/PS 0-1
- Any clinically significant disorder impacting the risk-benefit balance negatively per physician's judgment
- Any clinically significant gastrointestinal disorder, including hepatic disorders, bleeding, inflammation, occlusion, or diarrhea > grade 1
- Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months
- NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings
- Active infection or an unexplained fever >38.5°C (excluding tumor fever), which in the physician's opinion might compromise the patient's health
- Current use or any use in last two weeks of strong CYP3A-enzyme inducers/inhibitors and/or strong UGT1A inhibitors
- Known hypersensitivity to any of the components of liposomal irinotecan (Nal-IRI) other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, or leucovorin.
- Hypersensitivity to any of the active substances (tegafur, gimeracil, and oteracil)
- Previous treatment with fluoropyrimidine therapy
- Known dihydropyrimidine dehydrogenase (DPD) deficiency
- Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use a reliable method of birth control, during therapy and for 3 months following the last dose of liposomal irinotecan (Nal-IRI).
- Treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Academic Medical Center, Medical Oncology
Amsterdam, 1100 DD
J. W. Wilmink, MD, PhD, PhD, 31 20 5665955, j.w.wilmink@amsterdamumc.nl
Lyda ter Hofstede, 31 20 5668229, trialmedonc@amc.uva.nl
About this study
Official title: A Randomized Phase II Study of Second Line Treatment With Liposomal Irinotecan and S1 Versus Liposomal Irinotecan and 5-fluorouracil in Patients With Metastatic Pancreatic Cancer Who Failed on First Line Gemcitabine-based Chemotherapy
To determine the optimal second line treatment strategy in patients with metastatic pancreatic cancer who underwent a therapy with gemcitabine.
Read the detailed description
The 5-year survival of patients with pancreatic cancer is less than 5%. Despite improvements over the past years with the introduction of FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin and leucovorin) and gemcitabine and nab-paclitaxel, the vast majority will have disease recurrence or progression within 6 months. Single-arm phase II studies have been conducted after gemcitabine-based therapy. Randomized clinical trial data are limited in this setting, but the conclusion up to recently was that there is no superior chemotherapeutic regimen after gemcitabine failure. However, the NAPOLI trial altered the treatment landscape. In this trial, patients with metastatic pancreatic cancer that progressed after treatment with gemcitabine-based chemotherapy received liposomal irinotecan (nal-IRI) either as single agent or in combination with 5-fluorouracil/ leucovorin (5-FU/LV), or 5-FU/LV alone. Patients treated with the combination of nal-IRI plus 5-FU/LV experienced a median survival of 6.1 months versus 4.2 months for the 5-FU/LV group.
Recently, two studies on the clinical use of S-1 for pancreatic cancer have been reported from Japan. In the first study, S-1 demonstrated non-inferiority to gemcitabine in overall survival (OS) for advanced pancreatic cancer. In the second study, S-1 showed superiority to adjuvant chemotherapy with gemcitabine in OS. In addition to gemcitabine, S-1 is now regarded as the key drug in the management of pancreatic cancer in Japan. Phase II studies of S-1 in patients with gemcitabine-resistant pancreatic cancer have demonstrated moderate activity with acceptable toxicity. Although there has been no confirmed evidence based on phase III trials, S-1 would be a feasible treatment option in this patient population.
Objective:
To determine the optimal second line treatment strategy in patients with metastatic pancreatic cancer, whereby the hypothesis is, based on studies conducted in the Asian population, that the combination of S-1 and nal-IRI will be superior compared to 5-FU/ LV and nal-IRI, in terms of progression free survival. Therefore, patients will be randomized, after the optimal dose of S-1 and nal-IRI has been determined in the run in phase, between S-1 in combination with nal-IRI and 5-FU/LV in combination with nal-IRI during the phase II part of the study.
- Conditions
- Metastatic Pancreatic Cancer
- Being tested
- S1 + Nal-IRI, Nal-IRI+Leucovorin+5-FU
- Keywords
- Liposomal irinotecan, S1, Pancreatic cancer, Second line
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S1 + Nal-IRIDrug
S-1 will be given for 14 consecutive days, twice daily, followed by 2 weeks rest. Nal-IRI will be administered as an intravenous infusion on day 1 and 15. Courses of treatment will be repeated every 4 weeks.
Nal-IRI+Leucovorin+5-FUDrug
Nal-IRI 80 mg/m2 will be administered first, followed by LV 400 mg/m2, followed by 5-FU 2400 mg/m2 as an IV infusion over 46-hours on days 1-3. Each cycle consists of 14 days. Courses of treatment will be repeated every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| S1 and liposomal irinotecan | Experimental | S-1 will be given for 14 consecutive days, twice daily, followed by 2 weeks rest. Nal-IRI will be administered as an iv infusion on day 1 and 15. Treatment will be repeated every 4 wks. Receives: Drug: S1 + Nal-IRI; Drug: Nal-IRI+Leucovorin+5-FU |
| Liposomal irinotecan, Leucovorin and 5-fluoracil | Experimental | Nal-IRI 80 mg/m2 administered first, followed by LV 400 mg/m2, followed by 5-FU 2400 mg/m2 as an IV infusion over 46-hrs on days 1-3. Each cycle consists of 14 days. Treatment will be repeated every 2 wks. Receives: Drug: Nal-IRI+Leucovorin+5-FU |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT of Nal-IRI with S1
Dose limiting toxicity (DLT) of nal-IRI when co-administered with fixed dose S1 in patients with metastatic pancreatic cancer
Measured: 36 months
MTD of Nal-IRI with S1
Maximum tolerated dose (MTD) of nal-IRI when co-administered with fixed dose S1 in patients with metastatic pancreatic cancer
Measured: 36 months
Progression free survival of NaI-IRI with S1
Determination of the efficacy between the treatment arms in terms of progression free survival.
Measured: 36 months
Secondary outcomes (4)
Overall survival
To determine the overall survival (OS) benefit of nal-IRI combined with S-1, compared with nal-IRI combined with 5-FU/LV, in subjects pre-treated with gemcitabine based chemotherapy for metastatic pancreatic ductal adenocarcinoma.
Measured: 36 months
Response rate according to RECIST 1.1
To determine the response rate according to RECIST 1.1 of nal-IRI combined with S-1, compared with nal-IRI combined with 5-FU/LV, in subjects pre-treated with gemcitabine based chemotherapy for metastatic pancreatic ductal adenocarcinoma.
Measured: 36 months
Adverse events according NCI CTC version 4.0
To determine the adverse events according to NCI CTC version 4.0 of nal-IRI combined with S-1, compared with nal-IRI combined with 5-FU/LV, in subjects pre-treated with gemcitabine based chemotherapy for metastatic pancreatic ductal adenocarcinoma.
Measured: 36 months
Quality of life QoL (QLQ-C30)
To determine Quality of life (QoL) benefit of nal-IRI combined with S-1, compared with nal-IRI combined with 5-FU/LV, in subjects pre-treated with gemcitabine based chemotherapy for metastatic pancreatic ductal adenocarcinoma using a questionnaire QLQ-C30.Scale ranges 1-4, 1 is very good, 4 is very bad. Higher values represent a worse outcome.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2019
- Study start1 Dec 2019
- Primary completion1 Jan 2022 (estimated)
- Study completion1 Jan 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 122 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- UMC Utrecht, Isala, Maastricht University Medical Center, Vall de Hebron, Barcelona, Spain, University Hospital Verona, Italy, Odense University Hospital, Medical University of Vienna
- Responsible party
- Principal investigator, J.W. Wilmink, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- J W Wilmink, MD, PhD, Principal investigator, Ademic Medical Center Amsterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03986294
- Sponsor's protocol ID
- NL64126.018.17
- Acronym
- NAPAN
- Status last verified
- Jan 2021
- First submitted
- 11 Feb 2019
- Last updated
- 15 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gehrels AM, Pijnappel EN, van Daalen EH, Casalino S, Zechetto C, Quinzii A, Prager GW, de Vos-Geelen J, Macarulla T, Melisi D, Ali M, Wilmink JW. Second-line liposomal irinotecan plus S-1 vs. liposomal irinotecan plus 5-fluorouracil in metastatic pancreatic cancer: The phase I/II randomized NAPAN trial. Eur J Cancer. 2026 May 15;239:116683. doi: 10.1016/j.ejca.2026.116683. Epub 2026 Mar 20.
PubMed 41921365
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study of Second Line Treatment With Liposomal Irinotecan and S1 Versus Liposomal Irinotecan and 5-fluorouracil in Patients With Metastatic Pancreatic Cancer Who Failed on First Line Gemcitabine-based Chemotherapy
- ClinicalTrials.gov ID
- NCT03986294
- Acronym / sponsor ID
- NAPAN / NL64126.018.17
- Conditions
- Metastatic Pancreatic Cancer
- Keywords
- Liposomal irinotecan, S1, Pancreatic cancer, Second line
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 122 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- UMC Utrecht, Isala, Maastricht University Medical Center, Vall de Hebron, Barcelona, Spain, University Hospital Verona, Italy, Odense University Hospital, Medical University of Vienna
- Study start
- 1 Dec 2019 (actual)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 1 Jan 2022 (estimated)
- First posted
- 14 Jun 2019 (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.
To determine the optimal second line treatment strategy in patients with metastatic pancreatic cancer who underwent a therapy with gemcitabine.
Detailed description
The 5-year survival of patients with pancreatic cancer is less than 5%. Despite improvements over the past years with the introduction of FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin and leucovorin) and gemcitabine and nab-paclitaxel, the vast majority will have disease recurrence or progression within 6 months. Single-arm phase II studies have been conducted after gemcitabine-based therapy. Randomized clinical trial data are limited in this setting, but the conclusion up to recently was that there is no superior chemotherapeutic regimen after gemcitabine failure. However, the NAPOLI trial altered the treatment landscape. In this trial, patients with metastatic pancreatic cancer that progressed after treatment with gemcitabine-based chemotherapy received liposomal irinotecan (nal-IRI) either as single agent or in combination with 5-fluorouracil/ leucovorin (5-FU/LV), or 5-FU/LV alone. Patients treated with the combination of nal-IRI plus 5-FU/LV experienced a median survival of 6.1 months versus 4.2 months for the 5-FU/LV group.
Recently, two studies on the clinical use of S-1 for pancreatic cancer have been reported from Japan. In the first study, S-1 demonstrated non-inferiority to gemcitabine in overall survival (OS) for advanced pancreatic cancer. In the second study, S-1 showed superiority to adjuvant chemotherapy with gemcitabine in OS. In addition to gemcitabine, S-1 is now regarded as the key drug in the management of pancreatic cancer in Japan. Phase II studies of S-1 in patients with gemcitabine-resistant pancreatic cancer have demonstrated moderate activity with acceptable toxicity. Although there has been no confirmed evidence based on phase III trials, S-1 would be a feasible treatment option in this patient population.
Objective:
To determine the optimal second line treatment strategy in patients with metastatic pancreatic cancer, whereby the hypothesis is, based on studies conducted in the Asian population, that the combination of S-1 and nal-IRI will be superior compared to 5-FU/ LV and nal-IRI, in terms of progression free survival. Therefore, patients will be randomized, after the optimal dose of S-1 and nal-IRI has been determined in the run in phase, between S-1 in combination with nal-IRI and 5-FU/LV in combination with nal-IRI during the phase II part of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| S1 and liposomal irinotecan | Experimental | Drug: S1 + Nal-IRI, Drug: Nal-IRI+Leucovorin+5-FUS-1 will be given for 14 consecutive days, twice daily, followed by 2 weeks rest. Nal-IRI will be administered as an iv infusion on day 1 and 15. Treatment will be repeated every 4 wks. |
| Liposomal irinotecan, Leucovorin and 5-fluoracil | Experimental | Drug: Nal-IRI+Leucovorin+5-FUNal-IRI 80 mg/m2 administered first, followed by LV 400 mg/m2, followed by 5-FU 2400 mg/m2 as an IV infusion over 46-hrs on days 1-3. Each cycle consists of 14 days. Treatment will be repeated every 2 wks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects must satisfy all of the following inclusion criteria to be enrolled in the study.
- Able to understand and provide written informed consent
- ≥ 18 years of age
- Histologically or cytologically confirmed adenocarcinoma of pancreas
- Documented metastatic disease, according to RECIST 1.1.
Key exclusion criteria (19 listed)
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Serum total bilirubin ≥1.5 x ULN (biliary drainage is allowed for biliary obstruction)
- Severe renal impairment (CLcr ≤ 30 ml/min)
- Inadequate bone marrow reserves as evidenced by:
- WHO/PS 0-1
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 |
|---|---|---|
| S1 + Nal-IRIS-1 will be given for 14 consecutive days, twice daily, followed by 2 weeks rest. Nal-IRI will be administered as an intravenous infusion on day 1 and 15. Courses of treatment will be repeated every 4 weeks. | Drug | S1 and liposomal irinotecan |
| Nal-IRI+Leucovorin+5-FUNal-IRI 80 mg/m2 will be administered first, followed by LV 400 mg/m2, followed by 5-FU 2400 mg/m2 as an IV infusion over 46-hours on days 1-3. Each cycle consists of 14 days. Courses of treatment will be repeated every 2 weeks. | Drug | Liposomal irinotecan, Leucovorin and 5-fluoracil, S1 and liposomal irinotecan |
Primary outcome
DLT of Nal-IRI with S1
Time frame: 36 months
Dose limiting toxicity (DLT) of nal-IRI when co-administered with fixed dose S1 in patients with metastatic pancreatic cancer
MTD of Nal-IRI with S1
Time frame: 36 months
Maximum tolerated dose (MTD) of nal-IRI when co-administered with fixed dose S1 in patients with metastatic pancreatic cancer
Progression free survival of NaI-IRI with S1
Time frame: 36 months
Determination of the efficacy between the treatment arms in terms of progression free survival.
4 secondary outcomes
Overall survival
Time frame: 36 months
Response rate according to RECIST 1.1
Time frame: 36 months
Adverse events according NCI CTC version 4.0
Time frame: 36 months
Quality of life QoL (QLQ-C30)
Time frame: 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2021.
- Derived from this study: PubMed 41921365Gehrels AM, Pijnappel EN, van Daalen EH, Casalino S, Zechetto C, Quinzii A, Prager GW, de Vos-Geelen J, Macarulla T, Melisi D, Ali M, Wilmink JW. Second-line liposomal irinotecan plus S-1 vs. liposomal irinotecan plus 5-fluorouracil in metastatic pancreatic cancer: The phase I/II randomized NAPAN trial. Eur J Cancer. 2026 May 15;239:116683. doi: 10.1016/j.ejca.2026.116683. Epub 2026 Mar 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.
J W Wilmink, MD, PhD principal investigator
Ademic Medical Center Amsterdam
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing S1 + Nal-IRI and Nal-IRI+Leucovorin+5-FU in people with Metastatic Pancreatic Cancer, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
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 7 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 15 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact J W Wilmink, MD, PhD (31 20 5665955, j.w.wilmink@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLT of Nal-IRI with S1 (time frame: 36 months). The study lists 3 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 NCT03986294, which also lists 1 linked publication.
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 15 Jan 2021.