RecruitingPhase IIIInterventional

A randomized, open-label Phase III study of amivantamab and mFOLFOX6 or FOLFIRI versus cetuximab and mFOLFOX6 or FOLFIRI as first-line treatment in participants with KRAS/NRAS and BRAF wild-type unresectable or metastatic left-sided colorectal cancer

This clinical trial is testing a new treatment approach for adults with advanced left-sided bowel cancer (colorectal cancer) that has spread or cannot be removed by surgery. It focuses on tumours that do not have mutations in certain genes, known as KRAS, NRAS, and BRAF. Currently, standard care often includes chemotherapy alongside a targeted medicine called cetuximab. In this study, doctors want to find out if a newer targeted drug called amivantamab, given with chemotherapy, is more effective at controlling the cancer than the standard cetuximab combination. Participants are placed into one of two treatment groups by chance. Everyone in the trial receives chemotherapy, but one group gets amivantamab while the other gets cetuximab. Doctors will monitor everyone closely with regular scans, blood tests, and check-ups to track their health, response to treatment, and any side effects.

At a glance

Status

Recruiting

Phase

Phase III

Sponsor

Janssen-Cilag International NV

Enrolment target

1,000

Start

21 Oct 2024

Estimated completion

23 Dec 2026

Unresectable or Metastatic Left-sided Colorectal Cancer

What is this study about?

Bowel cancer, also called colorectal cancer, starts in the large bowel or back passage. In some people, the cancer starts on the left side of the bowel and may have spread to other parts of the body, meaning it cannot be cured by surgery alone. Cancer cells often rely on certain proteins on their surface to send signals that tell them to grow and multiply. Standard treatment usually involves chemotherapy combined with targeted drugs that block these growth signals.

Amivantamab is a new type of targeted antibody medicine. It is designed to latch onto two specific growth proteins (called EGFR and MET) on cancer cells, turning off their signals and helping the immune system fight the cancer. The current standard targeted drug, cetuximab, only blocks one of these proteins. Doctors want to see whether blocking both proteins with amivantamab works better at shrinking tumours or slowing cancer growth.

This trial is specifically for patients whose cancer cells do not carry changes in certain genes, known as KRAS, NRAS, and BRAF 'wild-type' tumours. Knowing your tumour's genetic makeup helps doctors predict which treatments are most likely to be helpful. By comparing amivantamab directly with cetuximab, this study aims to discover whether this new combination should become the new standard first-choice treatment.

Key takeaways

A Phase 3 trial comparing a new targeted drug (amivantamab) against standard treatment (cetuximab), both given with chemotherapy.
Aimed at adults with advanced, left-sided bowel cancer that cannot be removed by surgery.
Requires tumours to have normal (wild-type) KRAS, NRAS, and BRAF genes.
Participants are randomly assigned to one of two treatment groups.
Study medicines and tests are free, and travel expenses are reimbursed.

Who may be eligible?

This study is open to adults aged 18 and over who have been diagnosed with bowel cancer that started on the left side of the bowel or rectum. The cancer must be advanced, meaning it cannot be removed with an operation or has spread to other areas of the body (metastatic).

To take part, your tumour must be tested to confirm that it is 'wild-type' for the KRAS, NRAS, and BRAF genes, which simply means these genes do not have specific mutations. You must not have had previous chemotherapy or targeted therapy for advanced bowel cancer, although previous treatment given straight after surgery more than 12 months ago may be acceptable.

You will also need to be reasonably active and able to look after yourself in daily life, have acceptable blood, liver, and kidney test results, and agree to provide a small sample of tumour tissue for testing. Women must not be pregnant or breastfeeding, and effective contraception must be used during and for a period after the trial.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I am aged 18 or older.
I have been diagnosed with bowel cancer that started on the left side of the colon or rectum.
My cancer has spread or cannot be removed by an operation.
My tumour has been tested and does not have mutations in KRAS, NRAS, or BRAF genes.
I have not yet started chemotherapy or targeted medicine for advanced cancer.
I am well enough to carry out light daily activities.

Answer every question to see your result.

What does participation involve?

If you take part, you will first have a screening period lasting up to 28 days to make sure the trial is safe and suitable for you. This involves blood tests, urine tests, scans, and a tumour sample. If eligible, a computer will assign you by chance to one of two groups: one group receives amivantamab with chemotherapy, and the other receives cetuximab with chemotherapy. Neither you nor your doctor can choose your group.

You will receive your treatment at the hospital through an injection or a drip. Throughout the study, you will attend regular hospital appointments for check-ups, scans, and blood tests to see how the cancer is responding and to monitor your general health. You will also be asked to complete short questionnaires about how you are feeling. After treatment ends, the study team will continue to check on your health during a follow-up phase. The overall study will run for around four years, and travel and parking expenses for your visits will be reimbursed.

Potential risks and benefits

Taking part may help slow down or shrink your cancer, but this cannot be guaranteed as amivantamab is still being tested. However, you will receive close medical monitoring from a specialist cancer team, and your participation could help improve future treatments for people with bowel cancer. Like all cancer treatments, the medicines used can cause side effects. Common risks include skin rashes, tiredness, nausea, vomiting, diarrhoea, allergic reactions during infusions, and nerve tingling in the fingers or toes. Your care team will monitor you closely and give you treatments to help manage any side effects. You are free to leave the study at any time, for any reason, and your standard NHS care will not be affected.

Locations (9)

St. Bartholomews Hospital
City only
London, England
University College Hospital
Approximate
London, England
Castle Hill Hospital
Approximate
Cottingham, England
Western General Hospital
City only
Lothian, Scotland
Addenbrookes
Approximate
Cambridge, England
Royal Marsden Hospital
Unverified
Sutton, England
Mount Vernon Cancer Centre
Unverified
Northwood, England
Birmingham Heartlands Hospital
Unverified
Birmingham, England
St. James's University Hospital
Unverified
Leeds, England

Common questions

What does 'wild-type' mean?

'Wild-type' is a medical term meaning that a gene is normal and does not have a specific mutation. In this trial, it means your cancer does not carry changes in the KRAS, NRAS, or BRAF genes, making targeted therapies like amivantamab or cetuximab more likely to work.

Can I choose which treatment group I join?

No. A computer system puts participants into one of the two groups by chance. This process is called randomisation, and it is the fairest way to ensure the study results are reliable and unbiased.

Will I have to pay for the treatment?

No. The study medicines, tests, and scans are provided free of charge by the trial sponsor. Reasonable travel and parking costs for your hospital visits will also be reimbursed.

How is the trial medicine given?

Amivantamab is usually given as an injection under the skin, while cetuximab and the chemotherapies are given through a drip (infusion) into a vein at the hospital clinic.

What happens if I decide to stop taking part?

You can leave the trial at any point without giving a reason. Leaving the study will never affect the quality of your regular medical care or your relationship with your healthcare team.

How to find out more

S Linnington

Official trial record

Always speak to your GP or specialist before deciding to take part in a study.