CETUXIMAB for Metastatic colorectal cancer

Inclusion criteria

• {"criterion_text":"- Patient’s signed informed consent\n- Adequate hepatic function (all of the following): a. Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) b. ALAT and ASAT ≤ 2.5 x ULN (in the presence of hepatic metastases, ALAT and ASAT ≤ 5 x ULN) c. 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 (INR: 2.0 – 3.5; aPTT: 1.5 – 2.5 x ULN).\n- Adequate renal function: a. Creatinine clearance (calculated according to Cockcroft and Gault) ≥ 50 mL/min\n- Proficient fluorouracil metabolism as defined: a. Prior treatment with 5-FU or capecitabine without unusual toxicity b. If tested, normal DPD deficiency test according to the standard of the study site c. 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%\n- Women of childbearing potential (WOCBP) and men must agree to use highly effective contraceptive measures (Pearl index <1; e.g. combined oral and intravaginal, transdermal, injectable or implantable hormonal contraception; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner) 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 is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.\n- 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.\n- Histologically confirmed, UICC stage IV unresectable adenocarcinoma of the colon or rectum\n- Locally confirmed RAS/BRAF wild-type tumor status (KRAS and NRAS exon 2, 3, 4, BRAF exon 11/15)\n- Centrally confirmed RAS/BRAF wild-type status by liquid biopsy during screening phase\n- Age ≥18 at the time of written informed consent\n- ECOG performance status ≤1\n- Presence of at least one measurable reference lesion according to the RECIST 1.1 criteria\n- Archival tumor tissue available\n- Adequate bone marrow function (all of the following): a. Leukocytes ≥ 3.0 x 10E9/L with neutrophils ≥ 1.5 x 10E9/L b. Thrombocytes ≥ 100 x 10E9/L c. Hemoglobin ≥ 8 g/dL"}

Exclusion criteria

• {"criterion_text":"- 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.\n- Hemorrhagic diathesis or known thrombophilia\n- Known glucuronidation deficiency (Gilbert's syndrome) (specific screening not required)\n- Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before written informed consent.\n- 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\n- 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.\n- Active alcohol or drug abuse\n- Any other significant medical, psychiatric or social condition not covered by the above criteria, which, in the investigator’s judgement, may pose a safety risk, impair protocol compliance or interfere with reliable assessment of study outcomes\n- Pernicious anemia or other types of anemia caused by vitamin B12 deficiency\n- Concomitant use with St. John’s wort\n- Absent or restricted legal capacity\n- 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 inclusion in the study, depending on which period is longest or simultaneous participation in another study while taking part in the study\n- 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.\n- Acute or chronic New York Heart Association Class III or greater heart failure by clinical judgement.\n- Myocardial infarction, balloon angioplasty (PTCA) with or without stenting, and cerebral vascular accident (including TIA)/stroke within the past 12 months before randomization\n- Unstable angina pectoris\n- Unstable cardiac arrhythmia > grade 2 NCI CTCAE despite anti-arrhythmic therapy.\n- Active uncontrolled infection by investigator’s perspective.\n- Pre-existing pulmonary fibrosis or immune pneumonitis\n- Additional cancer treatment (chemotherapy, radiation, immunotherapy or hormone treatment) during the study treatment. Mistletoe therapy does not represent an exclusion criterion.\n- Patients who are institutionalized by order of court or public authority\n- Patients who might be dependent on the sponsor/investigator or the trial site\n- 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 CTCAE grade ≥ 3.\n- Known hypersensitivity to Chinese hamster ovary cell (CHO) –cellular products or other recombinant human or humanized monoclonal antibodies\n- 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.\n- History of acute or subacute intestinal occlusion, inflammatory bowel disease, immune colitis or chronic diarrhea\n- Symptomatic peritoneal carcinosis\n- Severe, non-healing wounds, ulcers or bone fractures"}

Primary endpoints

• {"endpoint_text":"- Time to Failure of Strategy, which is defined as the time from randomization to failure of the treatment strategy. Failure of the treatment strategy is defined as o Disease progression on treatment o Death o Unacceptable toxicity o Occurrence of resistance mechanisms by ctDNA analysis","definition_or_measurement_approach":"Time from randomization to failure of the treatment strategy; failure defined as disease progression on treatment, death, unacceptable toxicity, or occurrence of resistance mechanisms by ctDNA analysis."}

Secondary endpoints

• {"endpoint_text":"- Efficacy: • Progression-free survival (PFS)1 to PFSN (defined as each PFS from treatment start with FOLFIRI+cetuximab to the first disease progression in the respective treatment period) • TFS stratified by ctDNA-guided progression or radiological progression • Overall survival (OS) • Objective response rate (ORR)","definition_or_measurement_approach":"PFS defined as each PFS from treatment start with FOLFIRI+cetuximab to first disease progression in the respective treatment period; TFS stratified by ctDNA-guided progression or radiological progression; OS and ORR measured by standard oncology endpoints."}
• {"endpoint_text":"- Tumor response kinetics: • Dynamics of the tumor markers CEA and CA19-9 • Early tumour shrinkage, as determined by radiological imaging • Depth of radiological tumor response, as determined by radiological imaging","definition_or_measurement_approach":"Measured by serial tumor marker (CEA, CA19-9) assessments and radiological imaging for early tumour shrinkage and depth of response."}
• {"endpoint_text":"- Circulating tumour DNA (ctDNA): • Prospective validation to use ctDNA based RAS/BRAF mutational analysis in addition to tissue-based RAS testing to exclude RAS/BRAF mutant tumors from treatment using the Guardant360 liquid biopsy assay • Define a threshold in ctDNA change predicting progressive disease during treatment break using the Guardant360 liquid biopsy assay • Validate the formerly defined ctDNA threshold using the Guardant360 liquid biopsy assay to induce re-use of FOLFIRI + Cetuximab","definition_or_measurement_approach":"ctDNA assessed using the Guardant360 liquid biopsy assay for RAS/BRAF mutation analysis and for defining/validating ctDNA change thresholds predictive of progression."}
• {"endpoint_text":"- Safety: • Type, incidence, severity, and causal relationship to IMPs of non-serious adverse events and serious adverse events (severity evaluated according to CTCAE version 5.0)","definition_or_measurement_approach":"Adverse events collected and graded per CTCAE v5.0; causality assessed relative to IMPs."}
• {"endpoint_text":"- Quality of life: • QoL as assessed with the QoL questionnaire EQ-5D-5L","definition_or_measurement_approach":"QoL assessed using the EQ-5D-5L questionnaire."}

Germany

Earliest CTIS Part Ii Submission Date

13-11-2025

Latest Decision Or Authorization Date

20-11-2025

Processing Time Days

7

Number Of Sites

17

Number Of Participants

267

Primary sponsor

Full Name

Charite Universitaetsmedizin Berlin KöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Charite Universitaetsmedizin Berlin KöR","duties_or_roles":"1,10,12,6,7,8","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"ABF-Pharmazie GmbH & Co. KG","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"HELIOS Klinikum Berlin-Buch GmbH","duties_or_roles":"14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Krankenhaus Nordwest GmbH","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Klinikum St Marien Amberg","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"MVZ Labor Ravensburg GbR","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Klinikum Guetersloh gGmbH","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Muenchen Klinik gGmbH","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"HELIOS Klinikum Bad Saarow GmbH","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Labor Dr. Wisplinghoff GbR","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Kliniken der Stadt Koeln gGmbH","duties_or_roles":"14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"St. Elisabeth Gruppe GmbH Katholische Kliniken Rhein-Ruhr","duties_or_roles":"14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"St. Elisabeth Gruppe GmbH Katholische Kliniken Rhein-Ruhr (Herne-Sued site)","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Katholisches Klinikum Bochum gGmbH","duties_or_roles":"14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Charite Universitaetsmedizin Berlin KöR (Augustenburger Platz 1 site)","duties_or_roles":"14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Klinikum Guetersloh gGmbH (second entry)","duties_or_roles":"14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Kliniken der Stadt Koeln gGmbH (Merheim site)","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Katholisches Klinikum Bochum gGmbH (additional entry)","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"University Medical Center Hamburg-Eppendorf","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Krankenhaus Maria Hilf GmbH","duties_or_roles":"14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Krankenhaus Nordwest GmbH (additional entry)","duties_or_roles":"14","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"RKH Klinken Ludwigsburg-Bietigheim gGmbH (site contact)","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Labor Berlin Charite Vivantes GmbH","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}