A Phase II study of NUC-3373 in combination with other agents in patients with colorectal cancer
Research type
Research Study
Full title
A randomised, open-label, Phase II, dose/schedule optimisation study of NUC-3373/leucovorin/irinotecan plus bevacizumab (NUFIRI-bev) versus 5-FU/leucovorin/irinotecan plus bevacizumab (FOLFIRI-bev) for the treatment of patients with previously treated unresectable metastatic colorectal cancer
IRAS ID
1005654
Contact name
Stuart Grant
Contact email
Sponsor organisation
NuCana plc
Eudract number
2022-001459-17
Clinicaltrials.gov Identifier
Research summary
The purpose of this study is to test the anti-cancer activity of NUC-3373 when given in combination with other medicines that are approved for the treatment of patients with colorectal cancer. NUC 3373 will be combined with leucovorin (LV), irinotecan and bevacizumab (NUFIRI bev) and will be compared to 5-FU in combination with LV, irinotecan and bevacizumab (FOLFIRI-bev). This study will also explore the safety of the study treatments.
Summary of results
"The standard treatment for many people with advanced colorectal cancer (CRC) is a chemotherapy medicine called 5-FU. 5-FU is used in combination with other medicines that are commonly used in CRC, including leucovorin (LV), irinotecan and bevacizumab.
The Sponsor of this study has developed a new type of chemotherapy drug called NUC 3373, which is similar to 5-FU. However, there are several factors known to limit the effectiveness of 5-FU and NUC-3373 has been designed to overcome these limitations.
The researchers in this study wanted to learn about the anti-cancer activity (how a tumour responds to a drug) of NUC-3373 when given in combination with LV, irinotecan and bevacizumab (also known as NUFIRI-bev) and to compare it with the standard treatment of 5-FU in combination with LV, irinotecan and bevacizumab (also known as FOLFIRI-bev).
A total of 180 people with advanced CRC participated in the study and were 27 to 85 years old. The study took place France, Germany, Italy, Spain, the UK, and the US between April 2023 and August 2024.
This was an open-label study, which means the study doctors and participants knew which treatments participants were receiving.
The 180 participants in this study were randomly assigned to one of the following groups:
• NUFIRI-bev Q1W (weekly schedule)
• NUFIRI-bev Q2W (alternate weekly schedule)
• FOLFIRI-bev Q2W (alternate weekly schedule as per standard practice)
Out of the 180 participants, a total of 177 received the study treatments: 56 in the NUFIRI-bev Q1W group; 64 in the NUFIRI-bev Q2W group; and 57 in the FOLFIRI-bev group.
The participants visited the study clinic on Days 1 and 15 (in the NUFIRI-bev Q2W and FOLFIRI-bev Q2W groups) or on Days 1, 8, 15 and 22 (in the NUFIRI-bev Q1W group) of each 28-day cycle. On these visits, the participants received the study treatments and underwent a number of tests to make sure it was safe for them to continue in the study. The participants had a scan to measure their tumours every 8 weeks. The study doctors kept track of any medical problems reported by the participants or observed by the study doctors.
This is a summary of the main results from the study. These are the results from all participants combined for each treatment group. The individual results of each participant might be different and are not in this summary.
A pre-planned early analysis of the data in this study, also called an interim analysis, was carried out in August 2024. During this analysis, the data indicated that NUFIRI-bev was unlikely to improve the progression-free survival time of the participants compared to FOLFIRI-bev. Therefore, the sponsor decided to stop the study early.
To answer the main aim of the study, the researchers looked at “progression-free survival” (PFS). To measure PFS, the researchers looked at the time from the start of study treatment until the time half of the participants were still alive without their cancer getting worse. This is known as the median progression-free survival time.
It was found that the median PFS time was shorter in the NUFIRI-bev groups compared to the FOLFIRI-bev group:
• NUFIRI-bev Q1W: 5.7 months
• NUFIRI-bev Q2W: 5.5 months
• FOLFIRI-bev: 9.0 months
This means that participants in the FOLFIRI-bev group were more likely to live for longer without their cancer getting worse than participants in the NUFIRI-bev groups.
A higher number of participants had serious adverse reactions in the FOLFIRI-bev group (10 participants; 18%) than in the NUFIRI-bev Q1W (4 participants; 7%) or Q2W (8 participants; 13%) groups.
The most common serious adverse reactions in the NUFIRI-bev groups were diarrhoea (4 participants) and hypersensitivity (reaction to study drugs; 2 participants). The most common serious adverse reactions in the FOLFIRI-bev group were pulmonary embolism (blood clot in lung; 3 participants) and asthenia (weakness; 2 participants).
Similar numbers of participants had adverse reactions in all treatment groups: 54 in NUFIRI-bev Q1W (96%); 60 in NUFIRI-bev Q2W (94%); and 55 in FOLFIRI-bev (97%).
The most common adverse reactions in the NUFIRI-bev groups were nausea (61 participants; 51%), diarrhoea (60 participants; 50%), asthenia (37 participants; 31%), and vomiting (35 participants; 29%). The most common adverse reactions in the FOLFIRI-bev group were diarrhoea (26 participants; 46%), asthenia (25 participants; 44%), nausea (21 participants; 37%), neutropenia (low levels of a type of white blood cell: 16 participants; 28%), and stomatitis (mouth sores: 12 participants; 21%).
Other studies may or may not show that these side-effects were related to the study treatments. The results from several studies are often needed to decide what side-effects are actually caused by a treatment.
The results of this study have helped researchers learn more about using NUC-3373 in people with advanced CRC when given as part of the NUFIRI-bev combination treatment."REC name
East Midlands - Nottingham 2 Research Ethics Committee
REC reference
22/EM/0234
Date of REC Opinion
30 Jan 2023
REC opinion
Further Information Favourable Opinion