Cetuximab Standard or Dose Escalation in First Line Colorectal Cancer (Everest2)
Colorectal Cancer
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring colorectal cancer, K-Ras wildtype, first line metastatic, standard cetuximab + FOLFIRI, dose escalation cetuximab
Eligibility Criteria
Inclusion Criteria:
- Written informed consent (+ optional for PK and TR) must be given according to ICH/GCP and national/local regulations.
- Patient is at least 18 years of age.
- Patient's body weight is ≤ 120 kg.
- Histologically proven and measurable (RECIST criteria v.1.1) metastatic adenocarcinoma of the colon or rectum, not in a previously irradiated area.
- K-Ras wild type tumour eligible for treatment with cetuximab.
- Unresectable metastatic disease.
- Life expectancy of at least 12 weeks.
- WHO ECOG performance status: 0 or 1.
- Effective contraception for both male and female patients if the risk of conception exists.
- Adequate organ function.
Adequate bone marrow, hepatic and renal function (assessed within 14 days prior to study entry):
- Hemoglobin > 10.0 g/dL, absolute neutrophil count > 1.5 x 109/L, platelet count > 100 x 109/L
- ALAT, ASAT < 2.5 x ULN, up to < 5 x ULN in case of liver metastases
- Alkaline phosphatase < 2.5 x ULN
- Total bilirubin < 1.5 x ULN
- Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault)
Exclusion Criteria:
- Prior treatment for metastatic disease (adjuvant therapy with fluoropyrimidines +/-oxaliplatin based regimens allowed if stopped 6 months prior to registration on study).
- Prior treatment with EGFR inhibitor or chemotherapy with irinotecan in adjuvant settings.
- Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to study entry.
- Administration of any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment.
- Concurrent chronic systemic immune therapy, chemotherapy, radiation therapy or hormone therapy not indicated in the study protocol.
- Any active dermatological condition > grade 1.
- Brain metastasis (known or suspected).
- Significant impairment of intestinal absorption (e.g. chronic diarrhea, inflammatory bowel disease).
- Other uncontrolled concomitant illness, including serious uncontrolled intercurrent infection.
- Uncontrolled coronary artery disease and/or unstable angina, a history of a myocardial infarction within the last 12 months or heart failure NYHA class III or IV. High risk of uncontrolled arrhythmia.
- Known allergy or any other adverse reaction to any of the drugs or to any related compound.
- Known dihydropyrimidine dehydrogenase (DPD) deficiency.
- Gilbert disease.
- Previous (within 5 years) or concurrent malignancies at other sites with the exception of surgically cured or adequately treated carcinoma in-situ of the cervix and basal cell carcinoma of the skin.
- Organ allografts requiring immunosuppressive therapy.
- Pregnancy (absence confirmed by serum/urine beta human choriongonadotrophin in pre-menopausal women) or breast-feeding.
- Medical, social or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent.
Sites / Locations
- Universitätsklinik für Innere medizin, Klinishe abteilung für hämatologie und Onkologie
- LKH Leoben, abteilung f. innere Medizin
- AKH Linz, Innere Medizin 3, Zentrum für Hämatologie und medizinishe Onkologie
- Landeskrankenhaus Salzburg, Univ. Klinik für innere Medizin III, Universitätsklinikum der PMU
- Krankenanstalt Rudolfstiftung, 1 medizinishe Abteilung
- St Vincent Krankenhaus Betriebs GmbH
- Imelda Ziekenhuis
- Erasme Hospital
- Cliniques Universitaires St Luc
- AZ Middelares Gent
- UZ Gent
- Centre Hospitalier de Jolimont-Lobbes, Oncology Médicale
- AZ Groeninge
- UZ Gasthuisberg
- CHC Saint Joseph
- AZ Sint Maarten Mechelen/Duffel
- H. Hartziekenhuis
- AZ Turnhout (Campus St Elisabeth)
- Hôpital Avicennes
- Hôpital Saint-André
- Hopital Européen Georges Pompidou
- Centre Eugène Marquis
- CHU Charles Nicolle
- State Health Center
- Medical Center of the University of Pecs , National Institute Oncology
- Hospital Universitari Vall d'Hebron
- Institut Català d'Oncologia
- Hospital Universitario Marqués de Valdecilla
- Hospital Universitario Virgen del Rocío
- Hospital Clinico Universitario De Valencia
Arms of the Study
Arm 1
Arm 2
Other
Experimental
Arm B - standard dose of cetuximab
Arm A - dose escalation of cetuximab
Patients with skin toxicity grade 1-4 or other significant toxicity who are not eligible for dose escalation will continue on the standard dose of cetuximab 250 mg/m2 weekly. No comparison between arms was planned.
Patients with skin toxicity grade 0 will follow an increasing dose schedule: on days 22 and 29 they will receive 350 mg/m2 and from day 36 onwards, 500 mg/m2 weekly.