Continuous or Intermittent Cetuximab Plus FOLFIRI as First-line Treatment in RAS/BRAF Wild-type mCRC Patients

Launched by CHARITE UNIVERSITY, BERLIN, GERMANY · May 27, 2025

Keywords

ClinConnect Summary

This clinical trial is studying the effectiveness of a chemotherapy treatment called FOLFIRI combined with a drug called cetuximab for adults with advanced colorectal cancer that has spread to other parts of the body. The researchers want to find out if giving this treatment continuously or with scheduled breaks makes a difference in how well it works and in the quality of life for patients. They will also check if they can spot any worsening of the disease earlier using a new blood test, which might help doctors respond faster by restarting treatment.

To join the study, participants must be at least 18 years old and have a specific type of colorectal cancer that hasn't been treated before, among other health criteria. They will receive the chemotherapy and cetuximab, have blood tests every four weeks, and undergo imaging tests every three months to monitor their health. Participants will also fill out questionnaires about their quality of life during the study. This trial is not yet recruiting, but it offers an opportunity for eligible patients to contribute to important research that could improve treatment for colorectal cancer.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Patient's signed informed consent
• • 2. Histologically confirmed, UICC stage IV unresectable adenocarcinoma of the colon or rectum
• • 3. Locally confirmed RAS/BRAF wild-type tumor status (KRAS and NRAS exon 2, 3, 4, BRAF exon 11/15)
• • a) Note: A maximum of two cycles FOLFIRI is allowed prior to start of induction treatment until the molecular characterization is fully reported
• • 4. Centrally confirmed RAS/BRAF wild-type status by liquid biopsy during screening phase
• • 5. Age 18 or older at the time of written informed consent
• • 6. ECOG performance status below or equal 1
• • 7. Presence of at least one measurable reference lesion according to the RECIST 1.1 criteria
• • 8. Archival tumor tissue available
• • 9. Consent to storage, molecular and genetic profiling of tumor material and blood
• 10. Adequate bone marrow function:
• • 1. Leukocytes ≥ 3.0 x 109/L with neutrophils ≥ 1.5 x 109/L
• • 2. Thrombocytes ≥ 100 x 109/L
• • 3. Hemoglobin ≥ 8 g/dL)
• 11. Adequate hepatic function:
• • 1. Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
• • 2. ALAT and ASAT ≤ 2.5 x ULN (in the presence of hepatic metastases, ALAT and ASAT ≤ 5 x ULN)
• • 3. INR \< 1.5 and aPTT \< 1.5 x ULN (patients without anticoagulation). Therapeutic anticoagulation is allowed if INR and aPTT have remained stable within the therapeutic range for at least 2 weeks.
• 12. Adequate renal function:
• • a) Creatinine clearance (calculated according to Cockcroft and Gault) ≥ 50 mL/min
• 13. Proficient fluorouracil metabolism as defined:
• • 1. Prior treatment with 5-FU or capecitabine without unusual toxicity OR
• • 2. If tested, normal DPD deficiency test according to the standard of the study site OR
• • 3. If tested, in patients with DPD deficiency test with a CPIC activity score of 1.0-1.5 fluoropyrimidine dosage should be reduced by 50%
• • 14. Females of childbearing potential (FCBPs) and men must agree to use highly effective contraceptive measures (Pearl index \<1) or practice true abstinence from any heterosexual intercourse (true abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject) for the duration of the study treatment and for at least 6 months after last administration of study medication. A woman will be considered as being of childbearing potential unless she is at least 50 years old and moreover has gone through menopause for at least 2 years or has been surgically sterilized. For men: With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for 6 months after the last dose of study treatment. Men must refrain from donating sperm during this same period. With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 6 months after the last dose of study medication to avoid exposing the embryo.
• Exclusion Criteria:
• • 1. Proof of a RAS or BRAF mutation (KRAS/NRAS exons 2, 3, 4 or BRAF exon 15) in the tumor (proven in the primary tumor or metastasis) or liquid biopsy during screening phase.
• • 2. Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before written informed consent.
• • 3. New York Heart Association Class III or greater heart failure by clinical judgement.
• • 4. Myocardial infarction, balloon angioplasty (PTCA) with or without stenting, and cerebral vascular accident/stroke within the past 12 months before randomization
• • 5. Unstable angina pectoris
• • 6. Unstable cardiac arrhythmia \> grade 2 NCI CTCAE despite anti-arrhythmic therapy.
• • 7. Active uncontrolled infection by investigator's perspective.
• • 8. Pre-existing pulmonary fibrosis or immune pneumonitis
• • 9. Additional cancer treatment (chemotherapy, radiation, immunotherapy or hormone treatment) during the study treatment in first-line and third-line treatment (treatments that are conducted as part of an anthroposophical or homeopathic treatment approach, e.g. mistletoe therapy does not represent an exclusion criterion)
• • 10. Participation in a clinical study or experimental drug treatment within 30 days prior to written informed consent or within a period of 5 half-lives of the substances administered in a clinical study or during an experimental drug treatment prior to written informed consent, depending on which period is longest or simultaneous participation in another study while taking part in the study
• • 11. Known hypersensitivity or allergic reaction to any of the following substances: 5-fluorouracil, folinic acid, cetuximab, irinotecan and chemically related substances and/or hypersensitivity to any of the components in the formulations of the aforementioned substances, including known hypersensitivity reactions to monoclonal antibodies NCI CTC grade ≥ 3.
• • 12. Known hypersensitivity to Chinese hamster ovary cell (CHO) -cellular products or other recombinant human or humanized monoclonal antibodies
• • 13. Patients with known brain metastases or leptomeningeal disease. In case of clinical suspicion of brain metastasis, a cranial CT or MRI must be performed to rule out brain metastasis before study inclusion.
• • 14. History of acute or subacute intestinal occlusion, inflammatory bowel disease, immune colitis or chronic diarrhea
• • 15. Symptomatic peritoneal carcinosis
• • 16. Severe, non-healing wounds, ulcers or bone fractures
• • 17. Requirement for immunization with live vaccine including attenuated live vaccine from at least 4 weeks before begin of induction treatment until 6 months after the administration of IMPs.
• • 18. Hemorrhagic diathesis or known thrombophilia
• • 19. Known glucuronidation deficiency (Gilbert's syndrome) (specific screening not required)
• • 20. Treatment with nucleoside analogues including sorivudine or brivudine within 28 days before begin of induction treatment or requirement for concomitant antiviral treatment with sorivudine or brivudine or analogues
• • 21. History of a second primary malignancy during the past 5 years before written informed consent or during participation in the study, with the exception of a basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ, if these were treated curatively.
• • 22. Active alcohol or drug abuse
• • 23. Any significant adverse event that has not adequately resolved, severe acute or chronic concomitant disease or medical condition including psychiatric conditions (including recent i.e. within the past year or active suicidal ideation or behavior) or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
• • 24. Absent or restricted legal capacity
• • 25. Patients who are institutionalized by order of court or public authority
• • 26. Patients who might be dependent on the sponsor/investigator or the trial site