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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Ms
Claire
Dimbleby
-
ariel@leeds.ac.uk
Dr
David
Cairns
+44 113 3431477
ariel@leeds.ac.uk
More information about this study, what is involved and how to take part can be found on the study website.
Advanced colorectal cancer
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
Background and study aims
Not all bowel (colon) cancers are the same. It is known that tumours which start in the right side of the bowel (right-sided), behave differently than those on the left side. Patients with advanced cancer (cancer that has spread to other areas) whose tumours are right-sided do not tend to live as long as those with left-sided. Right-sided tumours may not respond as well to drugs used to treat cancer. It is therefore important for researchers to find ways to improve the treatments and cancer outcomes for patients with right-sided tumours.
Anti-EGFR agents (cetuximab and panitumumab) are drugs that switch off the growth signals from the Epidermal Growth Factor Receptor (EGFR), which is a protein on the cancer cell which makes cancer grow and spread. We know that if a protein (RAS) is altered and becomes abnormal on the tumour then a patient will not respond to treatment with anti-EGFR drugs. Doctors now test the tumours of all patients and only treat those patients without these abnormal RAS proteins (RAS-wt) with anti-EGFR drugs.
These drugs are available to patients in the UK with RAS-wt advanced bowel cancer alongside chemotherapy. However, in some patients with RAS-wt cancers the drugs do not work, despite the proteins being normal. This means that patients experience unpleasant side effects without any benefits. Cancer researchers have tried to understand why some patients benefit from anti-EGFR drugs, and some do not.
Research has shown that some patients with tumours that start in the right side of the bowel do not respond to this treatment and in many countries anti-EGFR drugs are not recommended for patients with a right-sided tumour. UK data shows that some patients with right-sided bowel cancers respond well to anti-EGFR drugs, but some patients do worse and their cancer grows more quickly and the side effects are more severe, than when treated with chemotherapy alone. This creates a problem for oncologists and patients. An extra test to help identify patients with right-sided bowel cancer that are most likely to benefit from anti-EGFR drugs would help resolve this.
Further research has found different tumour proteins (EREG and AREG) that identify those patients most likely to respond to anti-EGFR drugs, including patients with right-sided bowel cancers. Further research on the importance of this protein is needed before it can be used in clinics.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
You can take part if:
Current inclusion criteria as of 30/04/2024:
Inclusion criteria for registration:
1. Age >=18 years
2. Biopsy-confirmed adenocarcinoma of the colon with a right primary tumour location (defined as proximal to and including the splenic flexure)
3. aCRC defined as either M1 or locally inoperable disease.
4. Tumour RAS status either wild-type ( by local testing) or unknown
5. Tumour measurable by RECIST v1.1 criteria on CT scan (scans are not required to be reported to RECIST at site)
6. Pre-registration laboratory tests:
6.1. Neutrophils >=1.5 x10^9/l and platelet count >=100 x10^9/l
6.2. Serum bilirubin <=1.25 x upper limit of normal (ULN), alkaline phosphatase < = 5x ULN, and serum transaminase (either AST or ALT) <=2.5 x ULN
6.3. Estimated creatinine clearance >=50ml/min
7. Medically fit for the trial treatments
8. Sufficient tumour material for EREG/AREG analysis
9. Written informed consent for registration
Inclusion criteria for randomisation:
1. Registered in ARIEL
2. ARIEL central or local testing confirms tumour RAS-wt status
3. ARIEL central testing confirms tumour EREG/AREG high
4. Patients have had CT scan within the timeframes stipulated in the protocol. (If there is a contrast reaction, then non-contrast CT with MRI is acceptable assuming at least one of these modalities shows measurable disease at baseline for ETS evaluation and both modalities are repeated at the two trial timepoints at weeks 8 and 16.)
5. WHO performance status (PS) 0, 1 or 2
6. For women of childbearing potential, negative pregnancy test as per standard practice and adequate contraceptive precautions.
7. Effective contraception for male patients if the risk of conception exists.
8. Fit for combination chemotherapy plus c
You may not be able to take part if:
Exclusion criteria for registration:1. Tumour RAS-mutation present2. Prior chemotherapy for mCRC (may have received neoadjuvant or adjuvant chemotherapy provided disease did not progress on treatment, and > 6 months since last dose)3. Prior anti-EGFR agent therapy
Exclusion criteria for randomisation:1. Patient has received more than one cycle of chemotherapy since registration2. Women who are breastfeeding3. Patients with history of hypersensitivity to irinotecan, oxaliplatin, 5-fluorouracil or any of their excipients 4. Patients in receipt of live vaccine within four weeks prior to randomisation.5. Patients with a history interstitial pneumonitis/idiopathic lung disease (ILD)6. Patients with a history of keratitis, ulcerative keratitis or severe dry eye7. Patients with a history of severe skin reaction which in the clinicians opinion could be exacerbated by EGFR Mab (cf Steven’s Johnson Syndrome)
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Ms
Claire
Dimbleby
-
ariel@leeds.ac.uk
Dr
David
Cairns
+44 113 3431477
ariel@leeds.ac.uk
More information about this study, what is involved and how to take part can be found on the study website.
The study is sponsored by University of Leeds and funded by NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); National Institute for Health Research (NIHR) (UK).
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Or CPMS 50663
You can print or share the study information with your GP/healthcare provider or contact the research team directly.
