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A Study to Assess the Effectiveness and Safety of Irinotecan Liposome Injection, 5-fluorouracil/Leucovorin Plus Oxaliplatin in Patients Not Previously Treated for Metastatic Pancreatic Cancer, Compared to Nab-paclitaxel+Gemcitabine Treatment (NAPOLI 3)

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ClinicalTrials.gov Identifier: NCT04083235
Recruitment Status : Active, not recruiting
First Posted : September 10, 2019
Results First Posted : March 13, 2024
Last Update Posted : April 30, 2024
Sponsor:
Information provided by (Responsible Party):
Ipsen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Adenocarcinoma of the Pancreas
Interventions Drug: Irinotecan Liposomal Injection
Drug: Oxaliplatin
Drug: 5Fluorouracil
Drug: Leucovorin
Drug: Nab-paclitaxel
Drug: Gemcitabine
Enrollment 770
Recruitment Details This Phase 3, open-label study was conducted in participants with metastatic adenocarcinoma of the pancreas at 187 investigational sites in 18 countries (Australia, Brazil, Canada, Israel, Republic of Korea, United States, Austria, Belgium, Czechia, France, Germany, Greece, Hungary, Italy, Portugal, Spain, United Kingdom, and Russia). First participant was recruited on 11 February 2020 and data cut-off (DCO) date was 23 July 2022.
Pre-assignment Details This study consisted of a screening period (up to 28 days), treatment period (28-day cycles of treatment until radiologically determined disease progression per response evaluation criteria in solid tumors [RECIST 1.1]), unacceptable study medication related toxicity or withdrawal from study treatment followed by survival follow-up (until death or study closure, whichever occurred first). A total of 770 participants were randomized in 1:1 ratio using an interactive web response system (IWRS).
Arm/Group Title NALIRIFOX Nab-paclitaxel+Gemcitabine
Hide Arm/Group Description Participants were treated with irinotecan liposome injection 50 milligram per square meter (mg/m^2) followed by oxaliplatin 60 mg/m^2, followed by leucovorin (LV) 400 mg/m^2 and then 5-fluorouracil (FU) 2400 mg/m^2 intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent. Participants were treated with nab-paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Period Title: Overall Study
Started 383 387
Received Treatment 370 379
Completed 59 77
Not Completed 324 310
Reason Not Completed
Death             252             277
Withdrawal by Subject             13             17
Lost to Follow-up             1             1
Does not meet entry criteria             1             0
Did not receive treatment             13             8
Ongoing at the time of DCO             44             7
Arm/Group Title NALIRIFOX Nab-paclitaxel+Gemcitabine Total
Hide Arm/Group Description Participants were treated with irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2, followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent. Participants were treated with nab-paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent. Total of all reporting groups
Overall Number of Baseline Participants 383 387 770
Hide Baseline Analysis Population Description
The Intent-to-Treat (ITT) population consisted of all randomized participants to whom study treatment was assigned by randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 383 participants 387 participants 770 participants
62.8  (9.71) 64.0  (8.34) 63.4  (9.06)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 383 participants 387 participants 770 participants
Female 179 157 336
Male 204 230 434
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 383 participants 387 participants 770 participants
Hispanic or Latino 49 30 79
Not Hispanic or Latino 305 328 633
Unknown or Not Reported 29 29 58
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 383 participants 387 participants 770 participants
White 315 324 639
Not Reported 26 29 55
Asian 20 18 38
Black or African American 12 7 19
Other 7 6 13
Multiple 3 0 3
American Indian or Alaska Native 0 2 2
Native Hawaiian or Other Pacific Islander 0 1 1
1.Primary Outcome
Title Overall Survival (OS)
Hide Description The OS was defined as time from the date of randomization to the date of death due to any cause. Participants who did not have a date of death recorded at the time of the final analysis were censored at the last known time that the participant was alive. The median OS was measured using Kaplan-Meier technique.
Time Frame Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose, end of treatment (EoT) visit, then every 2 months thereafter up to DCO date of 23 July 2022 (maximum of 893 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all randomized participants to whom study treatment was assigned by randomization.
Arm/Group Title NALIRIFOX Nab-paclitaxel+Gemcitabine
Hide Arm/Group Description:
Participants were treated with irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2, followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Participants were treated with nab-paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 383 387
Median (95% Confidence Interval)
Unit of Measure: months
11.1
(10.0 to 12.1)
9.2
(8.3 to 10.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NALIRIFOX, Nab-paclitaxel+Gemcitabine
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments [Not Specified]
Method Stratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.70 to 0.99
Estimation Comments The HR and 95% confidence interval (CI) was based on a stratified Cox proportional hazards regression model, stratified by baseline Eastern Cooperative Oncology Group (ECOG) performance status, region and liver metastases as per IWRS.
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS was defined as the time from the date of randomization to the first documented disease progression using response evaluation criteria in solid tumors (RECIST) Version 1.1 as per Investigator assessment or death due to any cause. The median PFS was measured using Kaplan-Meier technique.
Time Frame Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose until EoT visit (maximum of 893 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all randomized participants to whom study treatment was assigned by randomization. Only participants with PFS event are reported.
Arm/Group Title NALIRIFOX Nab-paclitaxel+Gemcitabine
Hide Arm/Group Description:
Participants were treated with irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2, followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Participants were treated with nab-paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 249 259
Median (95% Confidence Interval)
Unit of Measure: months
7.4
(6.0 to 7.7)
5.6
(5.3 to 5.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NALIRIFOX, Nab-paclitaxel+Gemcitabine
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Stratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.58 to 0.83
Estimation Comments The HR and 95% CI was based on a stratified Cox proportional hazards regression model, stratified by baseline ECOG performance status, region and liver metastases as per IWRS.
3.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description The ORR was defined as the percentage of participants with a best overall response (BOR) characterized as either a complete response (CR) or partial response (PR) per RECIST Version 1.1. BOR was defined as the best response as recorded from randomization until documented objective disease progression using RECIST Version 1.1. As per RECIST version 1.1, CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions; and overall response = CR + PR. The ORR was calculated using Clopper-Pearson method.
Time Frame Assessments performed at baseline (within 28 days before start of study treatment), every 8 weeks after first dose until EoT visit, (maximum of 893 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population consisted of all randomized participants to whom study treatment was assigned by randomization.
Arm/Group Title NALIRIFOX Nab-paclitaxel+Gemcitabine
Hide Arm/Group Description:
Participants were treated with irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2, followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Participants were treated with nab-paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
Overall Number of Participants Analyzed 383 387
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
41.8
(36.8 to 46.9)
36.2
(31.4 to 41.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NALIRIFOX, Nab-paclitaxel+Gemcitabine
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.26
Confidence Interval (2-Sided) 95%
0.95 to 1.69
Estimation Comments OR, 95% CI and p-value were obtained from the Cochran-Mantel-Haenszel test adjusting by baseline ECOG performance status, region and liver metastases as per IWRS.
Time Frame Treatment-emergent adverse events are reported from the time of first study treatment administration (Day 1) up to DCO date of 23 July 2022 (maximum of 893 days)
Adverse Event Reporting Description The Safety population was a subset of the ITT population that received at least 1 dose (including a partial dose) of any component of the study medication in the combination.
 
Arm/Group Title NALIRIFOX Nab-paclitaxel+Gemcitabine
Hide Arm/Group Description Participants were treated with irinotecan liposome injection 50 mg/m^2 followed by oxaliplatin 60 mg/m^2, followed by LV 400 mg/m^2 and then 5-FU 2400 mg/m^2 IV infusion on Days 1 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent. Participants were treated with nab-paclitaxel 125 mg/m^2 followed by gemcitabine 1000 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle until disease progression, death, unacceptable study treatment-related toxicity or withdrawal of consent.
All-Cause Mortality
NALIRIFOX Nab-paclitaxel+Gemcitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   252/370 (68.11%)      277/379 (73.09%)    
Hide Serious Adverse Events
NALIRIFOX Nab-paclitaxel+Gemcitabine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   201/370 (54.32%)      195/379 (51.45%)    
Blood and lymphatic system disorders     
Anaemia † 1  5/370 (1.35%)  6 8/379 (2.11%)  8
Febrile neutropenia † 1  7/370 (1.89%)  9 6/379 (1.58%)  6
Neutropenia † 1  2/370 (0.54%)  2 1/379 (0.26%)  1
Pancytopenia † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Thrombocytopenia † 1  0/370 (0.00%)  0 2/379 (0.53%)  2
Disseminated intravascular coagulation † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Cardiac disorders     
Atrial fibrillation † 1  0/370 (0.00%)  0 3/379 (0.79%)  3
Cardiac arrest † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Cardiac failure † 1  0/370 (0.00%)  0 2/379 (0.53%)  2
Acute myocardial infarction † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Angina pectoris † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Arrhythmia † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Atrial flutter † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Cardiac failure chronic † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Cardiac flutter † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Myocardial infarction † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Sinus node dysfunction † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Tachycardia † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Ear and labyrinth disorders     
Vertigo † 1  2/370 (0.54%)  2 0/379 (0.00%)  0
Eye disorders     
Retinal vein occlusion † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Gastrointestinal disorders     
Diarrhoea † 1  23/370 (6.22%)  28 9/379 (2.37%)  9
Vomiting † 1  22/370 (5.95%)  26 6/379 (1.58%)  6
Nausea † 1  18/370 (4.86%)  24 3/379 (0.79%)  4
Abdominal pain † 1  9/370 (2.43%)  10 8/379 (2.11%)  8
Ascites † 1  6/370 (1.62%)  7 5/379 (1.32%)  6
Colitis † 1  7/370 (1.89%)  7 4/379 (1.06%)  4
Constipation † 1  1/370 (0.27%)  1 6/379 (1.58%)  6
Gastrointestinal haemorrhage † 1  3/370 (0.81%)  5 4/379 (1.06%)  4
Intestinal obstruction † 1  3/370 (0.81%)  3 2/379 (0.53%)  2
Ileus † 1  3/370 (0.81%)  3 1/379 (0.26%)  1
Upper gastrointestinal haemorrhage † 1  1/370 (0.27%)  1 3/379 (0.79%)  3
Duodenal obstruction † 1  2/370 (0.54%)  3 1/379 (0.26%)  1
Duodenal stenosis † 1  2/370 (0.54%)  2 1/379 (0.26%)  1
Duodenal ulcer † 1  3/370 (0.81%)  3 0/379 (0.00%)  0
Small intestinal obstruction † 1  1/370 (0.27%)  1 2/379 (0.53%)  2
Gastric haemorrhage † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Gastrointestinal toxicity † 1  2/370 (0.54%)  2 0/379 (0.00%)  0
Haematemesis † 1  2/370 (0.54%)  2 0/379 (0.00%)  0
Obstruction gastric † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Oesophagitis † 1  2/370 (0.54%)  2 0/379 (0.00%)  0
Pancreatitis acute † 1  0/370 (0.00%)  0 2/379 (0.53%)  4
Abdominal discomfort † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Abdominal pain upper † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Diarrhoea haemorrhagic † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Duodenal ulcer perforation † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Dysphagia † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Enterocolitis † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Faecaloma † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Food poisoning † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Gastric fistula † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Gastric ulcer haemorrhage † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Gastrointestinal disorder † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Intestinal pseudo-obstruction † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Mesenteric vein thrombosis † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Neutropenic colitis † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Odynophagia † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Oesophageal ulcer † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Oesophageal varices haemorrhage † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Small intestinal haemorrhage † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Terminal ileitis † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
General disorders     
Pyrexia † 1  8/370 (2.16%)  9 12/379 (3.17%)  14
Asthenia † 1  7/370 (1.89%)  7 2/379 (0.53%)  2
Fatigue † 1  7/370 (1.89%)  7 0/379 (0.00%)  0
General physical health deterioration † 1  1/370 (0.27%)  1 6/379 (1.58%)  6
Malaise † 1  3/370 (0.81%)  4 0/379 (0.00%)  0
Oedema peripheral † 1  0/370 (0.00%)  0 3/379 (0.79%)  3
Mucosal inflammation † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Peripheral swelling † 1  0/370 (0.00%)  0 2/379 (0.53%)  2
Catheter site inflammation † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Chest pain † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Condition aggravated † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Generalised oedema † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Inadequate analgesia † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Inflammation † 1  1/370 (0.27%)  2 0/379 (0.00%)  0
Multiple organ dysfunction syndrome † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Pain † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Performance status decreased † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Sudden cardiac death † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Sudden death † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Hepatobiliary disorders     
Cholangitis † 1  4/370 (1.08%)  4 6/379 (1.58%)  6
Biliary obstruction † 1  6/370 (1.62%)  6 1/379 (0.26%)  1
Cholestasis † 1  1/370 (0.27%)  1 2/379 (0.53%)  2
Hyperbilirubinaemia † 1  2/370 (0.54%)  2 1/379 (0.26%)  1
Cholecystitis † 1  0/370 (0.00%)  0 2/379 (0.53%)  2
Cholecystitis acute † 1  0/370 (0.00%)  0 2/379 (0.53%)  2
Bile duct stenosis † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Hepatitis † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Hepatitis toxic † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Hepatotoxicity † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Jaundice cholestatic † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Infections and infestations     
COVID-19 † 1  18/370 (4.86%)  18 14/379 (3.69%)  14
Pneumonia † 1  7/370 (1.89%)  7 13/379 (3.43%)  13
Sepsis † 1  6/370 (1.62%)  6 16/379 (4.22%)  18
Urinary tract infection † 1  3/370 (0.81%)  3 4/379 (1.06%)  4
Asymptomatic COVID-19 † 1  0/370 (0.00%)  0 3/379 (0.79%)  3
Biliary tract infection † 1  2/370 (0.54%)  2 1/379 (0.26%)  1
Cellulitis † 1  0/370 (0.00%)  0 3/379 (0.79%)  3
Febrile infection † 1  1/370 (0.27%)  1 2/379 (0.53%)  2
Gastroenteritis † 1  3/370 (0.81%)  3 0/379 (0.00%)  0
Abdominal sepsis † 1  0/370 (0.00%)  0 2/379 (0.53%)  2
Bacteraemia † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Diverticulitis † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Erysipelas † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Escherichia bacteraemia † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Septic shock † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Suspected COVID-19 † 1  0/370 (0.00%)  0 2/379 (0.53%)  2
Abdominal abscess † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Anal abscess † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Atypical pneumonia † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Bacterial sepsis † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Biliary sepsis † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
COVID-19 pneumonia † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Campylobacter colitis † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Catheter site infection † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Cholangitis infective † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Clostridium difficile colitis † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Device related bacteraemia † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Device related infection † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Enterococcal infection † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Gallbladder abscess † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Gastroenteritis norovirus † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Hepatic infection † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Hepatitis E † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Implant site cellulitis † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Infective spondylitis † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Large intestine infection † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Liver abscess † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Peritonitis bacterial † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Pneumonia aspiration † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Post procedural cellulitis † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Staphylococcal bacteraemia † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Streptococcal infection † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Injury, poisoning and procedural complications     
Exposure to SARS-CoV-2 † 1  0/370 (0.00%)  0 4/379 (1.06%)  4
Hip fracture † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Fall † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Femoral neck fracture † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Head injury † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Wound † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Investigations     
Blood bilirubin increased † 1  5/370 (1.35%)  5 3/379 (0.79%)  3
Neutrophil count decreased † 1  2/370 (0.54%)  2 2/379 (0.53%)  2
SARS-CoV-2 test positive † 1  1/370 (0.27%)  1 2/379 (0.53%)  2
Gamma-glutamyltransferase increased † 1  2/370 (0.54%)  2 0/379 (0.00%)  0
White blood cell count decreased † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Blood alkaline phosphatase increased † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Blood glucose abnormal † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
General physical condition abnormal † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Haemoglobin decreased † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Platelet count decreased † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Metabolism and nutrition disorders     
Dehydration † 1  10/370 (2.70%)  11 4/379 (1.06%)  4
Hypokalaemia † 1  6/370 (1.62%)  7 3/379 (0.79%)  4
Decreased appetite † 1  5/370 (1.35%)  5 2/379 (0.53%)  2
Hypoglycaemia † 1  1/370 (0.27%)  1 4/379 (1.06%)  5
Hyponatraemia † 1  1/370 (0.27%)  1 2/379 (0.53%)  2
Adult failure to thrive † 1  0/370 (0.00%)  0 2/379 (0.53%)  2
Failure to thrive † 1  0/370 (0.00%)  0 2/379 (0.53%)  2
Hypophosphataemia † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Diabetes mellitus inadequate control † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Diabetic metabolic decompensation † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Electrolyte imbalance † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Hypercalcaemia † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Hyperkalaemia † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Type 2 diabetes mellitus † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Chest wall haematoma † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Myalgia † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Pain in extremity † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Pathological fracture † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumour haemorrhage † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Peritumoural oedema † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Tumour pain † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Nervous system disorders     
Cerebrovascular accident † 1  4/370 (1.08%)  4 2/379 (0.53%)  2
Ischaemic stroke † 1  4/370 (1.08%)  4 2/379 (0.53%)  2
Cerebral haemorrhage † 1  2/370 (0.54%)  2 0/379 (0.00%)  0
Cerebral ischaemia † 1  2/370 (0.54%)  2 0/379 (0.00%)  0
Aphasia † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Cerebral infarction † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Embolic stroke † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Epilepsy † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Generalised tonic-clonic seizure † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Hemiparesis † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Hypoaesthesia † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Metabolic encephalopathy † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Myoclonus † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Pineal gland cyst † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Sciatica † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Seizure † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Transient ischaemic attack † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Tremor † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Product Issues     
Thrombosis in device † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Psychiatric disorders     
Confusional state † 1  1/370 (0.27%)  1 2/379 (0.53%)  2
Mental status changes † 1  2/370 (0.54%)  2 0/379 (0.00%)  0
Anxiety † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Delirium † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Depression † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Psychotic disorder † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Renal and urinary disorders     
Acute kidney injury † 1  3/370 (0.81%)  3 9/379 (2.37%)  10
Haematuria † 1  0/370 (0.00%)  0 3/379 (0.79%)  3
Renal impairment † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Nephrolithiasis † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Renal failure † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Urinary retention † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Urinary tract obstruction † 1  0/370 (0.00%)  0 1/379 (0.26%)  2
Reproductive system and breast disorders     
Penile vein thrombosis † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Priapism † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism † 1  10/370 (2.70%)  10 7/379 (1.85%)  7
Dyspnoea † 1  2/370 (0.54%)  2 5/379 (1.32%)  5
Pleural effusion † 1  2/370 (0.54%)  2 2/379 (0.53%)  2
Pneumonitis † 1  0/370 (0.00%)  0 2/379 (0.53%)  2
Pneumothorax † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Acute respiratory failure † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Aspiration † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Hydrothorax † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Hypoxia † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Interstitial lung disease † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Lung infiltration † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Pneumonitis aspiration † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Productive cough † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Pulmonary hypertension † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Respiratory failure † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Skin and subcutaneous tissue disorders     
Decubitus ulcer † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Erythema † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Pruritus † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Rash † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Vascular disorders     
Deep vein thrombosis † 1  4/370 (1.08%)  4 8/379 (2.11%)  8
Hypotension † 1  2/370 (0.54%)  2 3/379 (0.79%)  3
Embolism † 1  1/370 (0.27%)  1 3/379 (0.79%)  3
Haemorrhage † 1  0/370 (0.00%)  0 3/379 (0.79%)  3
Peripheral ischaemia † 1  1/370 (0.27%)  1 1/379 (0.26%)  1
Embolism arterial † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Hypertension † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Iliac vein occlusion † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Orthostatic hypotension † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
Peripheral embolism † 1  1/370 (0.27%)  1 0/379 (0.00%)  0
Venous thrombosis limb † 1  0/370 (0.00%)  0 1/379 (0.26%)  1
1
Term from vocabulary, MedDRA (25.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
NALIRIFOX Nab-paclitaxel+Gemcitabine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   364/370 (98.38%)      371/379 (97.89%)    
Blood and lymphatic system disorders     
Neutropenia † 1  108/370 (29.19%)  264 121/379 (31.93%)  278
Anaemia † 1  94/370 (25.41%)  134 151/379 (39.84%)  196
Thrombocytopenia † 1  50/370 (13.51%)  93 84/379 (22.16%)  173
Leukopenia † 1  18/370 (4.86%)  40 24/379 (6.33%)  43
Gastrointestinal disorders     
Diarrhoea † 1  258/370 (69.73%)  566 135/379 (35.62%)  221
Nausea † 1  215/370 (58.11%)  406 162/379 (42.74%)  216
Vomiting † 1  139/370 (37.57%)  222 96/379 (25.33%)  168
Stomatitis † 1  50/370 (13.51%)  81 45/379 (11.87%)  54
Constipation † 1  93/370 (25.14%)  115 113/379 (29.82%)  141
Abdominal pain † 1  92/370 (24.86%)  110 75/379 (19.79%)  80
Dry mouth † 1  28/370 (7.57%)  29 14/379 (3.69%)  16
Abdominal pain upper † 1  27/370 (7.30%)  34 21/379 (5.54%)  29
Flatulence † 1  30/370 (8.11%)  33 18/379 (4.75%)  21
Dyspepsia † 1  23/370 (6.22%)  32 18/379 (4.75%)  20
Abdominal distension † 1  22/370 (5.95%)  26 13/379 (3.43%)  15
Haemorrhoids † 1  19/370 (5.14%)  22 12/379 (3.17%)  13
General disorders     
Fatigue † 1  120/370 (32.43%)  173 143/379 (37.73%)  183
Asthenia † 1  110/370 (29.73%)  164 101/379 (26.65%)  166
Oedema peripheral † 1  52/370 (14.05%)  60 107/379 (28.23%)  134
Mucosal inflammation † 1  50/370 (13.51%)  60 16/379 (4.22%)  20
Pyrexia † 1  33/370 (8.92%)  43 84/379 (22.16%)  129
Chills † 1  6/370 (1.62%)  6 19/379 (5.01%)  20
Infections and infestations     
Urinary tract infection † 1  27/370 (7.30%)  29 23/379 (6.07%)  29
Investigations     
Neutrophil count decreased † 1  73/370 (19.73%)  208 69/379 (18.21%)  126
Platelet count decreased † 1  39/370 (10.54%)  71 67/379 (17.68%)  109
Weight decreased † 1  82/370 (22.16%)  92 33/379 (8.71%)  34
Alanine aminotransferase increased † 1  45/370 (12.16%)  64 48/379 (12.66%)  64
Aspartate aminotransferase increased † 1  40/370 (10.81%)  58 40/379 (10.55%)  55
White blood cell count decreased † 1  16/370 (4.32%)  24 32/379 (8.44%)  54
Gamma-glutamyltransferase increased † 1  44/370 (11.89%)  54 34/379 (8.97%)  35
Blood alkaline phosphatase increased † 1  39/370 (10.54%)  42 31/379 (8.18%)  33
Blood bilirubin increased † 1  21/370 (5.68%)  23 22/379 (5.80%)  23
Metabolism and nutrition disorders     
Decreased appetite † 1  132/370 (35.68%)  157 68/379 (17.94%)  136
Hypokalaemia † 1  116/370 (31.35%)  190 49/379 (12.93%)  70
Dehydration † 1  35/370 (9.46%)  40 29/379 (7.65%)  31
Hypoalbuminaemia † 1  26/370 (7.03%)  33 30/379 (7.92%)  31
Hypomagnesaemia † 1  34/370 (9.19%)  44 16/379 (4.22%)  22
Hyponatraemia † 1  18/370 (4.86%)  21 20/379 (5.28%)  21
Musculoskeletal and connective tissue disorders     
Myalgia † 1  13/370 (3.51%)  15 31/379 (8.18%)  43
Back pain † 1  28/370 (7.57%)  37 33/379 (8.71%)  36
Arthralgia † 1  13/370 (3.51%)  16 30/379 (7.92%)  41
Muscular weakness † 1  17/370 (4.59%)  22 21/379 (5.54%)  24
Pain in extremity † 1  7/370 (1.89%)  8 30/379 (7.92%)  35
Nervous system disorders     
Neuropathy peripheral † 1  66/370 (17.84%)  89 66/379 (17.41%)  92
Dysgeusia † 1  63/370 (17.03%)  74 58/379 (15.30%)  67
Peripheral sensory neuropathy † 1  56/370 (15.14%)  79 51/379 (13.46%)  60
Paraesthesia † 1  44/370 (11.89%)  53 33/379 (8.71%)  41
Dizziness † 1  24/370 (6.49%)  25 40/379 (10.55%)  44
Headache † 1  23/370 (6.22%)  37 19/379 (5.01%)  24
Polyneuropathy † 1  16/370 (4.32%)  19 19/379 (5.01%)  20
Neurotoxicity † 1  21/370 (5.68%)  35 13/379 (3.43%)  22
Psychiatric disorders     
Insomnia † 1  28/370 (7.57%)  28 32/379 (8.44%)  32
Anxiety † 1  10/370 (2.70%)  10 24/379 (6.33%)  25
Respiratory, thoracic and mediastinal disorders     
Epistaxis † 1  14/370 (3.78%)  15 43/379 (11.35%)  49
Dyspnoea † 1  24/370 (6.49%)  28 45/379 (11.87%)  48
Pulmonary embolism † 1  20/370 (5.41%)  20 24/379 (6.33%)  24
Cough † 1  14/370 (3.78%)  18 30/379 (7.92%)  31
Skin and subcutaneous tissue disorders     
Alopecia † 1  52/370 (14.05%)  53 119/379 (31.40%)  120
Rash † 1  11/370 (2.97%)  12 34/379 (8.97%)  37
Rash maculo-papular † 1  3/370 (0.81%)  3 25/379 (6.60%)  30
Pruritus † 1  12/370 (3.24%)  14 22/379 (5.80%)  26
Vascular disorders     
Hypotension † 1  21/370 (5.68%)  27 25/379 (6.60%)  26
Hypertension † 1  21/370 (5.68%)  24 15/379 (3.96%)  19
1
Term from vocabulary, MedDRA (25.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Ipsen Pharma
Phone: see email
EMail: clinical.trials@ipsen.com
Layout table for additonal information
Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT04083235    
Other Study ID Numbers: D-US-60010-001
2018-003585-14 ( EudraCT Number )
First Submitted: September 6, 2019
First Posted: September 10, 2019
Results First Submitted: February 15, 2024
Results First Posted: March 13, 2024
Last Update Posted: April 30, 2024