NAPOLI III - Irinotecan Liposome injection in Pancreatic Cancer
Research type
Research Study
Full title
An open-label, randomised, multicentre, phase III study of irinotecan liposome injection, oxaliplatin, 5-fluorouracil/leucovorin versus nab-paclitaxel plus gemcitabine in subjects who have not previously received chemotherapy for metastatic adenocarcinoma of the pancreas.
IRAS ID
274214
Contact name
Richard Hubner
Contact email
Sponsor organisation
Ipsen Bioscience Inc.
Eudract number
2018-003585-14
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 6 months, 3 days
Research summary
Research Summary:
This study, called NAPOLI 3, is a clinical study to learn about a treatment called irinotecan liposome injection for people with metastatic pancreatic ductal adenocarcinoma.
Metastatic pancreatic ductal adenocarcinoma is a type of cancer that starts in the pancreas and then spreads to other parts of the body. Pancreatic cancers are hard to diagnose early as they often have no early warning signs. Treatments aim to shrink the cancer and slow its spread to keep patients alive with a good quality of life for as long as possible.
Irinotecan is a medicine that works by blocking a protein called Topoisomerase-1 that helps cells multiply. When Toposiomerase-1 becomes too active, it can cause cancer cells to grow. By blocking Topoisomerase-1, irinotecan helps stop the cancer from growing.
In this study, researchers compared the effects and safety of a combination treatment called NALIRIFOX containing irinotecan liposome injection to a standard first-line combination treatment—nab-paclitaxel given with gemcitabine (Gem+NabP). The aim of this study was to compare the effects and safety of NALIRIFOX with Gem+NabP in participants who had not received chemotherapy for cancer of the pancreas that has spread to other parts of the body.
The study started in February 2020. It was conducted at 187 hospital centers in 18 countries worldwide. The study ended in February 2025.
770 participants took part (434 men and 336 women).
Average age: 63 years.
To be eligible to take part in the study, participants had to be:
• aged 18 years or older
• diagnosed with cancer of pancreas that had spread to other part(s) of the body, and
able to perform normal daily tasks and take care of themselves.
Participants were not eligible to take part in the study if:
• they had been treated for cancer of the pancreas with medicines, chemotherapy, radiation or surgery,
• they had a health condition that made them illegible to participate, as advised by a doctor.
NALIRIFOX (Study treatment)
The following drugs were given into the vein on Days 1 and 15 of each cycle. Participants received these treatments in cycles. Each cycle was 28 days long.
• irinotecan liposome injection 50 mg/m2,
• oxaliplatin 60 mg/m2 infusion,
• 5‑fluorouracil 2400 mg/m2, and
• leucovorin 400 mg/m2 infusion.
Gem + NabP (Standard treatment)
The following drugs were given into the vein on Days 1, 8 and 15 of each cycle. Participants received these treatments in cycles. Each cycle was 28 days long.
• Nab-paclitaxel 125 mg/m2 infusion, and
• Gemcitabine 1000 mg/m2 infusion.
Note: mg/m2 is a way to measure the drug dose given to participants. For example, 50 mg/m2 means 50 milligrams will be given for each square meter (area) of a participant’s body.
The study was conducted in three stages
Screening: The study doctor checked if participants could take part in this study, based on defined criteria. This was done within 28 days before starting the treatment.
Treatment: 770 eligible participants were assigned randomly to one of the two treatment arms based on: their ability to perform normal daily tasks and take care of themselves, where they lived, and whether the cancer had spread to their liver.
Out of the 770 participants randomly assigned, 749 received the study treatment presented as follows:
- NALIRIFOX Arm (370 participants)
- Gem + NabP Arm (379 participants)
21 participants have not received the study treatment because they decided to leave the study, their cancer worsened before the start of the treatment, or they ended up not being eligible to take part in the study. If a participant’s cancer got worse or they had an unacceptable adverse effect due to the study treatment, the treatment was stopped. This was an “open-label” study. This means that the participants and the study team knew which treatments the participants would receive. The participants’ health was monitored throughout the study by the study doctor.
Follow-up: Participants returned to the study site one month after their last dose of study treatment for health evaluation performed by the doctor. After that, they were followed up every two months by telephone, email, or a clinic visit until the study ended, to confirm their overall health and wellbeing.
Participants treated with NALIRIFOX lived for 2 months longer than those who received nab-paclitaxel and gemcitabine On average, participants on NALIRIFOX lived 2 months longer (11.1 months) compared with participants on Gem+NabP (9.2 months) after the start of the treatment.
Participants treated with NALIRIFOX lived longer than those receiving Gem+NabP.
Overall survival: 11.1 months vs 9.2 months.
Progression-free survival: 7.4 months vs 5.6 months.
Tumor response: 42% vs 36%.
Participants on NALIRIFOX lived 7.4 months without their cancer getting worse, compared to 5.6 months for those who were on Gem+NabP.
42% (160 out of 383) of participants on NALIRIFOX had their cancer decrease or completely disappear, compared to 36% (140 out of 387) of participants on Gem+NabP. During the study, participants were asked to report any ‘adverse events’, i.e. if they felt unwell, experienced any kind of medical event, or noticed anything different about their bodies.
If the study doctor thinks an adverse event may be related to the study treatment, it is called a ‘side effect’. A side effect is considered ‘serious’ when it is life-threatening, causes lasting problems, or leads to hospitalization. The overall summary of side effects in each group is presented below:
94% of participants experienced side effects.
23% experienced serious side effects.
2% died due to side effects.
25% discontinued treatment due to side effects.
The most common serious side effects participants experienced in any group were diarrhoea, vomiting, and feeling sick (the desire to vomit).
There were no new safety concerns for either of the combinations.This is an open-label, randomized, phase III study to evaluate the efficacy and safety of the irinotecan liposome injection + oxaliplatin + 5-FU/LV combination compared to nab-paclitaxel + gemcitabine as first-line treatment in adult patients with metastatic pancreatic cancer. The researchers and patients will know which treatment the patient will be receiving.
Patients will be randomized on a 1:1 ratio (there’s a 50% chance of receiving either) to one of the following treatment regimens:• Arm 1: irinotecan liposome injection + oxalaplatin + 5-FU/LV
• Arm 2: nab-paclitaxel + gemcitabineApproximately 750 patients will be recruited at approximately 200-220 clinical sites across North America, South America, Europe and Australia. The study will consist of:
• A screening period of 28 days
• A treatment phase 28 day cycles until disease progression
• A follow up phase until the end of the studyThere is no pre-determined duration for patients receiving treatment on either arm, it is intended that patients will be treated until disease progression, withdrawal from the study or unacceptable levels of toxicity related to the study medication.
Patients will undergo safety and tolerability assessments throughout the study that include but not limited to: physical examination, blood draws, CT Scans and questionnaires.REC name
East Midlands - Leicester South Research Ethics Committee
REC reference
20/EM/0087
Date of REC Opinion
7 May 2020
REC opinion
Further Information Favourable Opinion