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Testing continuous versus intermittent treatment with cetuximab, fluorouracil, folinic acid, and irinotecan in patients with newly diagnosed metastatic colorectal cancer

Fast replyRegistered drugNo placebo
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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study is looking at metastatic colorectal cancer, which is cancer that started in the colon or rectum and has spread to other parts of the body. The study will use a combination of medications including cetuximab, fluorouracil, folinic acid, and irinotecan. The combination of fluorouracil, folinic acid, and irinotecan is commonly called FOLFIRI. Cetuximab is a type of medicine that targets specific proteins on cancer cells. The study will only include patients whose cancer does not have certain genetic changes in genes called RAS and BRAF, which are known as wild-type tumors. The purpose of the study is to find out whether giving the treatment with planned breaks works better than giving it continuously without breaks.

Patients in this study will be divided into two groups by chance. One group will receive FOLFIRI plus cetuximab continuously without planned breaks. The other group will receive the same treatment for eight cycles, then have a planned break from treatment. If the cancer starts growing again during the break, the treatment will be restarted. The study will track how long the treatment strategy works before it fails, which could happen if the cancer gets worse, if side effects become too severe, if certain resistance markers appear in blood tests, or if death occurs. All medications will be given through a vein as an infusion.

During the study, patients will have regular check-ups and tests to see how the cancer is responding to treatment and to monitor for any side effects. Blood samples will be taken to look for tumor genetic material in the blood, which can help doctors understand if the cancer is responding to treatment or developing resistance. Quality of life will also be measured using questionnaires. The study will compare the two different ways of giving the same treatment to see which approach is better for patients with this type of cancer.

The research process

The trial runs in 8 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Initial treatment period

    Treatment will begin with a combination of chemotherapy medications and a targeted therapy. This phase consists of 8 treatment cycles.

    The treatment includes four medications administered through intravenous infusion (directly into a vein): fluorouracil, cetuximab, folinic acid, and irinotecan. This combination is referred to as FOLFIRI plus cetuximab.

    Each cycle follows a specific schedule determined by the treatment protocol. The exact dosage and frequency of each medication will be determined based on individual clinical parameters.

    During this period, regular monitoring will be performed to assess how the treatment is working and to check for any side effects.

  2. Step 2

    Treatment assignment

    After completing the initial 8 cycles, assignment to one of two treatment approaches will occur through randomization (a process similar to a coin flip that ensures fairness).

    One approach involves taking a planned treatment break after the initial 8 cycles, with treatment restarting if the disease begins to progress during the break.

    The other approach involves continuous treatment without a planned break, continuing with the same medications.

    The assignment to either approach is random and neither the patient nor the medical team can choose which approach will be followed.

  3. Step 3

    Treatment break or continuous treatment phase

    If assigned to the treatment break approach, medication will be stopped after the initial 8 cycles. Regular monitoring will continue during this break period.

    If assigned to continuous treatment, the same combination of fluorouracil, cetuximab, folinic acid, and irinotecan will continue beyond the initial 8 cycles without interruption.

    The duration of either approach depends on how the disease responds and how well the treatment is tolerated.

  4. Step 4

    Monitoring during treatment break

    For those assigned to the treatment break approach, regular assessments will be performed to monitor the disease status.

    These assessments include imaging scans to check if the cancer is growing and blood tests to measure tumor markers and circulating tumor DNA (ctDNA), which are small pieces of cancer DNA that can be detected in the blood.

    The ctDNA tests help determine if the disease is beginning to progress even before it can be seen on imaging scans.

  5. Step 5

    Re-starting treatment after a break

    If the disease shows signs of progression during the treatment break, treatment with the same combination of medications (FOLFIRI plus cetuximab) will be restarted.

    Disease progression may be detected through imaging scans or through changes in ctDNA levels in the blood.

    Treatment will resume with fluorouracil, cetuximab, folinic acid, and irinotecan administered through intravenous infusion, following the same protocol as the initial treatment period.

  6. Step 6

    Ongoing monitoring and assessments

    Throughout the entire study period, regular monitoring will occur to assess treatment effectiveness and safety.

    This includes imaging scans to measure tumor size and check for disease progression according to RECIST 1.1 criteria (a standardized method for measuring tumor response).

    Blood tests will be performed regularly to check liver function, kidney function, and blood cell counts, as well as to measure tumor markers (CEA and CA19-9) and ctDNA levels.

    Quality of life will be assessed using a questionnaire called EQ-5D-5L, which asks about mobility, self-care, usual activities, pain or discomfort, and anxiety or depression.

    Any side effects or adverse events will be documented and evaluated according to CTCAE version 5.0, a standard system for grading the severity of side effects.

  7. Step 7

    Treatment continuation or modification

    Treatment will continue as long as it remains effective and tolerable.

    Treatment may be stopped or modified if the disease progresses despite treatment, if unacceptable side effects occur, if resistance mechanisms are detected through ctDNA analysis, or if other medical reasons require stopping.

    The total duration of participation in the study depends on individual response to treatment and tolerability.

  8. Step 8

    Contraception requirements

    If applicable, highly effective contraception must be used throughout the treatment period and for at least 6 months after the last dose of study medication.

    This requirement applies to prevent potential harm to an unborn child, as the medications used in this study can cause serious birth defects.

Who can join the trial?

15 criteria

  • You must sign a form agreeing to take part in the study after receiving all necessary information
  • You must be at least 18 years old when you sign the consent form
  • You must have adenocarcinoma of the colon or rectum, which is a type of cancer that starts in the cells lining these organs, confirmed by examining tissue under a microscope
  • Your cancer must be stage IV, meaning it has spread to other parts of the body, and cannot be removed by surgery
  • Your tumor must be RAS and BRAF wild-type, which means your cancer cells do not have certain genetic changes in the KRAS, NRAS, and BRAF genes. This will be confirmed by local testing
  • Your RAS and BRAF wild-type status must also be confirmed by a central laboratory using a blood test called liquid biopsy during the screening period
  • You must have at least one tumor that can be measured using imaging scans according to specific measurement rules
  • You must have stored tumor tissue samples available from a previous biopsy or surgery
  • Your general health status must be good, with an ECOG performance status of 0 or 1, which means you are able to walk and carry out light work or fully active
  • Your liver must be working adequately, shown by blood tests: bilirubin, a substance produced when red blood cells break down, must be no more than 1.5 times the normal upper limit; liver enzymes called ALAT and ASAT must be no more than 2.5 times the normal upper limit, or no more than 5 times if cancer has spread to your liver; blood clotting tests called INR and aPTT must be less than 1.5 times normal if you are not on blood thinners, or stable within the recommended range if you are taking blood thinners
  • Your kidneys must be working adequately, with a creatinine clearance, which measures how well your kidneys filter waste, of at least 50 milliliters per minute
  • Your body must be able to process fluorouracil, a chemotherapy drug, properly. This is shown by either having received similar drugs before without unusual side effects, or having normal results on a DPD deficiency test that checks for an enzyme needed to break down this drug. If you have partial DPD deficiency with a specific score, the drug dose may be reduced by half
  • Your bone marrow must be working adequately, shown by blood tests: white blood cells, which fight infection, must be at least 3.0 x 10E9 per liter with neutrophils, a type of white blood cell, at least 1.5 x 10E9 per liter; platelets, which help blood clot, must be at least 100 x 10E9 per liter; hemoglobin, which carries oxygen in your blood, must be at least 8 grams per deciliter
  • If you are a woman who can become pregnant, you must agree to use highly effective birth control methods with less than 1% failure rate, or avoid sexual intercourse completely, during the study and for at least 6 months after the last dose of study medication
  • If you are a man with a female partner who can become pregnant, you must use a condom plus another birth control method with less than 1% failure rate together, or avoid sexual intercourse completely, during the study and for 6 months after the last dose. You must not donate sperm during this time. If your partner is pregnant, you must use a condom or avoid sexual intercourse during treatment and for 6 months after

Who cannot join the trial?

13 criteria

  • Previous chemotherapy treatment for cancer that has spread to other parts of the body (this is called metastatic disease)
  • Having changes or mutations in genes called RAS or BRAF - these are specific genes in cancer cells that are tested in the laboratory
  • Having received treatment with medicines called EGFR inhibitors before - these are drugs that block a specific protein on cancer cells
  • Being allergic or having had serious reactions to cetuximab - the study medicine - or similar drugs
  • Having serious heart problems or heart disease that is not well controlled
  • Having active infections that require treatment
  • Having other types of cancer within the last 5 years, except for certain non-dangerous skin cancers or early cervical cancer that was completely treated
  • Being pregnant or breastfeeding
  • Having severe problems with kidneys or liver that affect how these organs work
  • Having brain metastases - meaning cancer has spread to the brain - that are not stable or controlled
  • Not being able to take medicines by mouth or having problems with the digestive system that prevent proper absorption of medicines
  • Having conditions that affect the immune system or taking medicines that weaken the immune system
  • Not being willing or able to follow the study requirements and attend scheduled visits
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Investigated drugs

  • Cetuximab

    is a medication that targets a specific protein on cancer cells to help stop them from growing. It is given through a vein and works by blocking signals that tell cancer cells to multiply and spread.

  • FOLFIRI

    is a combination of three chemotherapy drugs used to treat colorectal cancer. It works by stopping cancer cells from growing and dividing. This treatment is given through a vein and helps shrink tumors or slow down their growth.

What is already known about the treatment

Cetuximab – Cetuximab is a medication given through an intravenous infusion (directly into a vein) that is approved and widely used in cancer treatment, particularly for metastatic colorectal cancer in patients whose tumors have specific genetic characteristics (RAS/BRAF wild-type). It works by blocking a protein called EGFR (epidermal growth factor receptor) on the surface of cancer cells, which prevents the cells from receiving signals that tell them to grow and divide, ultimately helping to slow or stop tumor growth. This medication belongs to a class of drugs called monoclonal antibodies or targeted cancer therapies, and it is typically used in combination with chemotherapy regimens like FOLFIRI to improve treatment outcomes for patients with advanced bowel cancer that has spread to other parts of the body.

Investigated diseases

Metastatic Colorectal Cancer – This is a type of cancer that starts in the colon or rectum and has spread to other parts of the body. The disease begins when cells in the colon or rectum grow out of control and form a tumor. Over time, cancer cells can break away from the original tumor and travel through the blood or lymph system to distant organs such as the liver, lungs, or other tissues. This spreading process is called metastasis. As the disease progresses, new tumors develop in these distant locations, which can affect the normal function of those organs. The condition represents an advanced stage of colorectal cancer where the disease is no longer confined to its original location.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2025-522377-12-00Protocol codeAIO-KRK-0524/FIRE-11Estimated enrolment267 patientsSponsorCharite Universitaetsmedizin Berlin KöR

sourced from the EU Clinical Trials Register and site verification

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