ANICCA-Class II
Research type
Research Study
Full title
A phase II trial assessing nivolumab in strong class II expressing microsatellite stable colorectal cancer
IRAS ID
237804
Contact name
Gary Middleton
Contact email
Sponsor organisation
University of Birmingham
Eudract number
2018-000318-39
Duration of Study in the UK
7 years, 0 months, 1 days
Research summary
Research Summary:
In 2014 there were over 41,000 new cases of colorectal cancer (CRC) in the UK and nearly 16,000 deaths from the disease, making it the second commonest cause of cancer death.Previous trials have shown that tumours with certain genetic problems identified in the laboratory, known as microsatellite instability (MSI) respond well to immunotherapy drugs. However, most people with colorectal cancer will not have this particular genetic problem in their tumour, known as microsatellite stablility (MSS) and these drugs do not work as well for these patients.
An immunohistochemistry test has been developed to assess the level of a molecule called Class II in colorectal tumours. We think that MSS bowel tumours with stronger levels of Class II molecules respond better to nivolumab, in the same way that MSI tumours respond. We estimate that about 1 in 10 people tested will have a high level of the class II molecule.
The purpose of this trial is to see if an immunotherapy drug called nivolumab is an effective treatment for this group of patients. The trial aims to find out if nivolumab provides a durable clinical benefit in halting further growth or spread of the cancer for at least 6 months and if it is effective enough to justify further testing in patients with MSS colorectal cancer with strong class II levels. To look at whether the cancer is responsive to nivolumab, computed tomography (CT) scans will be used to look at the tumour(s) and measure if they are getting bigger or smaller.
This is a single arm phase II trial, with a total duration of 4 years (18 months recruitment, two years treatment and 5 years follow up of patients)
Summary of Results:
In the ANICCA clinical trial (ISRCTN40245896), adults with a type of bowel cancer called microsatellite stable (MSS) cancer that had grown into tissue around the bowel or spread to another part of the body, were treated with a new immunotherapy drug called nivolumab.
Researchers wanted to find out if immunotherapy would work better for people whose cancer cells had a specific protein on them. The protein is called major histocompatibility complex (MHC) class 2. It can help make the cancer cell more visible to the immune system. Patients were treated with nivolumab that helps the immune system to find and kill cancer cells.
Patients in this trial were tested to see how well the nivolumab worked for people with MSS bowel cancer that has a high level of the class 2 protein, and if this worked well enough to routinely test people for this protein. The results showed that nivolumab does not work better for people with MSS bowel cancer that has the MHC class 2 protein.
Patients on this trial had treatment every 4 weeks; each 4-week period is called one cycle of treatment. Patients had between 1 and 8 cycles of treatment. All patients received 480 mg nivolumab by a single 60-minute intravenous infusion every cycle.
Between 28-Aug-2019 and 06-Sep-2021, 35 patients were registered to ANICCA. The trial was closed slightly earlier than planned (35 of a target of 36 patients recruited) due to the results of the trial not being as good as hoped.
33 patients were evaluable for response, which assessed how well their treatment had worked, about 6 months after they started treatment; for three people the cancer stayed the same, for 25 people the cancer had continued to grow and five people had died. How long it was until the cancer had started to grow in half the people taking part was also looked at. This is called the progression free survival and was found to be 9 weeks. How long it was until half the people taking part had died was also looked at. This is called the overall survival and was found to be just over 7 months. The trial also looked in more detail at how people did with this type of bowel cancer if it had spread to the liver. It was found that nivolumab worked better for people whose cancer had not spread to the liver.
In total, there were 529 adverse events (AE) reported in all patients. The most common events reported were abdominal pain, fever, fatigue and vomiting. 48 of these events, between 25 participants, were considered Serious Adverse Events. Events can be considered serious for several reasons, but usually because they require hospital admission, are life-threatening or result in death.
It was hard to draw firm conclusions from the trial because of the small number of people who took part. Sometimes trials show a different treatment isn’t useful for a particular type or stage of cancer, but these trials still add to our knowledge and understanding of cancer and how to treat it.
The results support further investigation to be carried out to find treatments for people with this type of bowel cancer that has spread to the liver.REC name
South Central - Oxford B Research Ethics Committee
REC reference
19/SC/0107
Date of REC Opinion
11 Jun 2019
REC opinion
Further Information Favourable Opinion