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Comparing irinotecan plus cetuximab with trifluridine and tipiracil plus bevacizumab for patients with metastatic colorectal cancer as third line treatment

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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 compare two different treatment combinations to see which one works better for patients who have already received two previous treatments. One treatment combination includes irinotecan given together with cetuximab. The other treatment combination includes trifluridine and tipiracil hydrochloride (given as a tablet called Lonsurf) together with bevacizumab. The purpose of the study is to find out which treatment combination is better at making the cancer shrink or disappear.

Patients in this study will be divided into two groups, and each group will receive one of the two treatment combinations. The treatments will be given over a period of up to 30 months. Irinotecan and cetuximab are given through a vein, while trifluridine and tipiracil hydrochloride are taken by mouth as tablets, and bevacizumab is given through a vein. The study will look at how well each treatment works by checking if the cancer gets smaller or goes away completely using imaging scans. Doctors will also monitor patients for any side effects from the treatments.

During the study, patients will have regular check-ups that include blood tests, physical examinations, and imaging scans to see how the cancer is responding to treatment. The study will also measure how long patients live without their cancer getting worse and their overall survival time. Additionally, patients will be asked to complete questionnaires about their quality of life to understand how the treatments affect their daily activities and well-being. The study requires patients to have specific genetic characteristics in their cancer, which will be tested using a blood test that looks for cancer cells circulating in the bloodstream.

The research process

The trial runs in 10 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Baseline assessment and blood test

    At the beginning of the trial, a blood sample will be collected to perform a specialized test called FoundationOne CDx. This test analyzes circulating tumor DNA to determine specific characteristics of the cancer.

    Blood will also be tested to confirm that pregnancy is not present if applicable.

    Physical examination will be performed, and vital signs will be measured.

    An electrocardiogram will be conducted to assess heart function.

    Blood tests will be performed to check blood cell counts, liver function, and kidney function.

    Imaging scans will be performed to measure the size and location of tumors according to RECIST 1.1 criteria, which is a standardized method for evaluating tumor response.

    A quality of life questionnaire called EORTC QLQ-C30 will be completed.

  2. Step 2

    Random assignment to treatment group

    Based on the results of the baseline tests, assignment to one of two treatment groups will occur. The specific treatment group cannot be chosen, as it is determined randomly.

    One group will receive irinotecan plus cetuximab, and the other group will receive trifluridine/tipiracil plus bevacizumab.

  3. Step 3

    Treatment with irinotecan plus cetuximab (if assigned to this group)

    Irinotecan is a medication that interferes with cancer cell growth. It will be administered through a vein or through a specialized method called intraportal infusion.

    Cetuximab is a medication that targets specific proteins on cancer cells. It will be administered through a vein as an infusion.

    The exact dosage, frequency, and duration of administration will be determined by the treating physician based on individual medical needs and response to treatment.

    Treatment will continue until the disease progresses or unacceptable side effects occur.

  4. Step 4

    Treatment with trifluridine/tipiracil plus bevacizumab (if assigned to this group)

    Trifluridine/tipiracil is available as film-coated tablets containing 20 mg of trifluridine and 8.19 mg of tipiracil hydrochloride. These medications work together to interfere with cancer cell growth and will be taken by mouth.

    Bevacizumab is a medication that blocks the formation of new blood vessels that feed tumors. It will be administered through a vein as an infusion.

    The exact dosage, frequency, and duration of administration will be determined by the treating physician based on individual medical needs and response to treatment.

    Treatment will continue until the disease progresses or unacceptable side effects occur.

  5. Step 5

    Regular monitoring during treatment

    Throughout the treatment period, regular visits will be scheduled to monitor health status and treatment response.

    Physical examinations will be performed, and vital signs will be measured at each visit.

    Blood tests will be conducted regularly to monitor blood cell counts, liver function, and kidney function.

    Any side effects or adverse events will be recorded and assessed using the NCI-CTCAE version 5.0, which is a standardized system for grading the severity of side effects.

    Electrocardiograms may be performed periodically to monitor heart function.

    Performance status will be assessed using the ECOG Performance Status scale, which measures how the disease affects daily living abilities.

  6. Step 6

    Imaging assessments

    Imaging scans will be performed at regular intervals to evaluate how the tumors are responding to treatment.

    These scans will be sent to an external radiology department where they will be reviewed by a specialist who does not know which treatment group was assigned.

    The images will be assessed using RECIST 1.1 criteria to determine if tumors have shrunk, remained stable, or grown.

  7. Step 7

    Quality of life assessments

    At specified time points during the trial, the EORTC QLQ-C30 questionnaire will be completed.

    This questionnaire asks about physical symptoms, emotional well-being, and how the disease and treatment affect daily activities.

    Responses will help assess how the treatment impacts overall quality of life.

  8. Step 8

    Contraception requirements during treatment

    If applicable, adequate contraception methods must be used throughout the trial and for at least 6 months after the last dose of treatment.

    Acceptable methods include abstinence, intrauterine devices, oral contraceptives, or double-barrier methods.

    Both the patient and their partner must agree to avoid pregnancy during this period.

  9. Step 9

    Treatment continuation or discontinuation

    Treatment will continue as long as it is providing benefit and side effects remain manageable.

    If imaging shows that the disease is progressing, or if unacceptable side effects occur, treatment will be stopped.

    The treating physician will discuss the results of assessments and any decisions regarding treatment continuation.

  10. Step 10

    Follow-up after treatment ends

    After treatment ends, follow-up visits will continue to monitor overall health status.

    Information about survival and disease status will be collected as part of the trial objectives.

    The duration of follow-up will be determined by the trial protocol and individual circumstances.

Who can join the trial?

20 criteria

  • You must be 18 years of age or older
  • You must be able to perform daily activities with little or no help, meaning you are up and about more than half of your waking hours
  • You must have a confirmed diagnosis of colorectal cancer, which is cancer that starts in the colon or rectum, confirmed by laboratory examination of tissue or cells
  • You must have at least one measurable tumor that can be seen and measured on scans
  • Your cancer must not have certain genetic changes called KRAS, NRAS, or BRAFV600E mutations, which are specific alterations in genes that affect how cancer grows
  • You must have previously received treatment with a medication targeting EGFR, which is a protein on cancer cells, and this treatment must have worked well for at least 6 months before your cancer started growing again
  • You must have received and had your cancer grow despite a second treatment that did not include EGFR-targeting or irinotecan medications
  • You must have had at least 4 months without receiving any EGFR-targeting treatment
  • Your cancer must have stopped responding to previous treatments with certain chemotherapy drugs including 5-fluorouracil or capecitabine, irinotecan, oxaliplatin, and bevacizumab
  • You must have a special blood test showing that your cancer does not have certain genetic changes in RAS, BRAF, EGFR, PIK3CAex20, MAP2K1, or MET genes, and does not have extra copies of the HER2 gene
  • Your life expectancy must be at least 3 months
  • Your blood counts must be adequate, meaning you have enough white blood cells that fight infection, neutrophils which are a type of white blood cell, lymphocytes which are immune cells, platelets that help blood clot, and hemoglobin which carries oxygen in your blood
  • Your liver function must be adequate, measured by levels of bilirubin, a substance produced when breaking down red blood cells, and liver enzymes called AST and ALT
  • Your kidney function must be adequate, measured by how well your kidneys filter waste from your blood
  • You must not have any medical reasons that would make it unsafe for you to receive the study medications
  • You must not have previously been treated with trifluridine/tipiracil, which is a specific chemotherapy medication
  • If you are a woman who can become pregnant, you must have a negative pregnancy test before starting the study
  • If you are a woman who can become pregnant or a man, you must agree to use effective birth control methods during the study and for at least 6 months after your last dose of study treatment
  • You must be willing and able to follow all study requirements and procedures
  • You must sign a consent form showing you understand and agree to participate in the study

Who cannot join the trial?

3 criteria

  • The source data does not provide specific exclusion criteria, which are reasons why a patient cannot participate in the study
  • Without detailed exclusion criteria information, it is not possible to list specific conditions or situations that would prevent participation in this clinical trial
  • Typically, exclusion criteria may include things like other serious medical conditions, certain medications being taken, or previous treatments, but these specific details are not available in the provided information
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Investigated drugs

  • Irinotecan

    is a cancer medication used to treat colorectal cancer. It works by stopping cancer cells from growing and dividing.

  • Cetuximab

    is a targeted therapy medication that blocks certain proteins on cancer cells to help slow or stop their growth. It is used to treat colorectal cancer.

  • Trifluridine/tipiracil

    is a combination cancer medication that interferes with the growth of cancer cells. It is used to treat advanced colorectal cancer.

  • Bevacizumab

    is a targeted therapy medication that blocks the formation of new blood vessels that tumors need to grow. It is used to treat various types of cancer including colorectal cancer.

What is already known about the treatment

  • Irinotecan

    Irinotecan is a chemotherapy medication given through an intravenous infusion into a vein, commonly used to treat advanced colorectal cancer that has spread to other parts of the body. It works by blocking an enzyme called topoisomerase I, which cancer cells need to copy their DNA and multiply, ultimately causing the cancer cells to die. This drug belongs to a class of medications called topoisomerase inhibitors and is well-established in cancer treatment protocols. In this clinical trial, irinotecan is being combined with cetuximab to evaluate its effectiveness as a third-line treatment option for patients with metastatic colorectal cancer.

  • Cetuximab

    Cetuximab is a targeted therapy medication administered as an intravenous infusion, used in the treatment of metastatic colorectal cancer. It is a type of monoclonal antibody that attaches to a specific protein called EGFR on the surface of cancer cells, blocking signals that tell the cells to grow and divide. This medication is approved and widely used in clinical practice for treating certain types of colorectal cancer. In this study, cetuximab is being tested in combination with irinotecan as a rechallenge therapy for patients whose disease has progressed after previous treatments.

  • Trifluridine/Tipiracil

    Trifluridine/tipiracil is an oral chemotherapy medication taken by mouth in tablet form, approved for treating metastatic colorectal cancer in patients who have already received other treatments. The medication contains two components: trifluridine, which gets incorporated into the DNA of cancer cells and stops them from growing, and tipiracil, which helps trifluridine stay active in the body longer by preventing its breakdown. This combination drug belongs to the class of nucleoside metabolic inhibitors and represents an established treatment option for advanced colorectal cancer. In this trial, it is being compared with the irinotecan plus cetuximab combination, both given alongside bevacizumab.

  • Bevacizumab

    Bevacizumab is a targeted therapy medication given through intravenous infusion, widely used in treating various cancers including metastatic colorectal cancer. It is a monoclonal antibody that works by blocking a protein called VEGF, which tumors use to create new blood vessels for their growth and spread, effectively starving the tumor of nutrients and oxygen. This medication belongs to the class of angiogenesis inhibitors and is well-established in cancer treatment. In this clinical trial, bevacizumab is being administered in combination with trifluridine/tipiracil as a comparator treatment arm.

Investigated diseases

Metastatic Colorectal Cancer – This is an advanced stage of colorectal cancer where the disease has spread from the colon or rectum to distant parts of the body. The cancer begins in the inner lining of the colon or rectum and grows through the layers of the intestinal wall. As it progresses, cancer cells break away from the original tumor and travel through the bloodstream or lymphatic system to other organs. Common sites where the cancer spreads include the liver, lungs, and distant lymph nodes. The disease develops when abnormal cells in the colon or rectum continue to multiply uncontrollably and gain the ability to invade other tissues. Metastatic colorectal cancer represents the most advanced form of the disease, where it is no longer confined to the area where it started.
Trial detailsLast updated 2 Oct 2026
Age18+ yearsPhasePhase IITrial ID2025-521319-38-00Estimated enrolment150 patientsSponsorGruppo Oncologico Dell'Italia Meridionale

sourced from the EU Clinical Trials Register and site verification

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