AIO-KRK-0114/ FIRE-4
Phase III, , Investigator initiierte Studie (IIT), Peer Reviewed, Multizentrisch, National
>= 18 Jahre
Molekulare Marker:
Inclusion Criteria: Histologically confirmed, UICC stage IV adenocarcinoma of the colon or rectum (metastatic colorectal cancer), primarily nonresectable or with surgery refused by the patient RAS wild-type tumour status (KRAS and NRAS exon 2-4) (proven in the primary tumour or metastasis) at any timepoint of randomisation Age ≥18 ECOG performance status 0-1 Patients suitable for chemotherapy administration Patient's written declaration of consent obtained Estimated life expectancy > 3 months Presence of at least one measurable reference lesion according to the RECIST 1.1 criteria (chest and abdominal CT 4 weeks or less before randomisation) Primary tumour tissue available and patient consents to storage and molecular and genetic profiling of blood, plasma and tumour material (patients included directly at Part 2 of the study in whom primary tumour material is no longer available may be included in the study, provided that tumour material from the compulsory biopsy on progression following second-line treatment is available). Effective contraceptive measures in men and in women of childbearing age (Pearl index <1) Adequate haematopoietic function: Leukocytes ≥ 3.0 x 109/L with neutrophils ≥ 1.5 x 109/L Thrombocytes ≥ 100 x 109/L, Haemoglobin ≥ 5.6 mmol/L (equivalent to 9 g/dL) Adequate hepatic function: Serum bilirubin ≤ 1.5 x upper normal limit, ALAT and ASAT ≤ 2.5 x upper normal limit (in the presence of hepatic metastases, ALAT and ASAT ≤ 5 x upper normal limit) INR < 1.5 and aPTT < 1.5 x upper normal limit (patients without anticoagulation). Therapeutic anticoagulation is allowed if INR and aPTT have remained stable within the therapeutic range for at least 2 weeks. Adequate renal function: Serum creatinine ≤ 1.5 x upper normal limit or creatinine clearance (calculated according to Cockcroft and Gault) ≥ 50ml/min. adequate cardiac function: ECG and echocardiogram with a LVEF of ≥55% Any significant toxicities of previous treatments must have resolved or stabilised Last administration of an anti-EGFR substance ≥ 4 months before randomisation 2 Inclusion criterion solely for Part 1: No previous chemotherapy for metastatic disease Time since last administration of a previous adjuvant chemotherapy >6 months Additional inclusion criteria solely for Part 2: Former first-line treatment of the metastatic colorectal cancer with FOLFIRI and cetuximab; data available for the duration of treatment and the response within the context of first-line treatment Former second-line treatment of the colorectal cancer without FOLFIRI, irinotecan or an anti-EGFR substance with data available for the substances administered, duration of treatment and response within the context of the second-line treatment Proof of a RAS wild-type tumour (KRAS and NRAS exons 2-4) in a tumour biopsy (metastasis) within 4 weeks before randomisation CT examinations with evidence of a partial response (PR) or complete response (CR) or stable disease (SD) ≥6 months according to RECIST Version 1.1 criteria as best response within the context of the first-line treatment with FOLFIRI and cetuximab Exclusion Criteria: Proof of a RAS mutation (KRAS or NRAS, exons 2-4 in the tumour (proven in the primary tumour or metastasis) or absence of testing for RAS mutation Primarily resectable metastases and the patient wishes for resection Grade III or IV heart failure (NYHA classification) Myocardial infarction, unstable angina pectoris, balloon angioplasty (PTCA) with or without stenting within the past 12 months before inclusion in the study Pregnancy (exclusion to be ascertained by a beta hCG test) or breast feeding Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study Additional cancer treatment (chemotherapy, radiation, immune therapy or hormone treatment) during the study treatment in first-line and third-line treatment (treatments that are conducted as part of an anthroposophic or homeopathic treatment approach, e.g. mistletoe therapy do not represent an exclusion criterion) Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before entering the study (exclusion criterion solely for part 1) Participation in a clinical study or experimental drug treatment within 30 days prior to inclusion or during participation in the study Known hypersensitivity or allergic reaction to any of the following substances: 5-fluorouracil, cetuximab, oxaliplatin, irinotecan, bevacizumab and chemically related substances Known or clinically suspected brain metastases History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhoea Symptomatic peritoneal carcinosis Severe, non-healing wounds, ulcers or bone fractures Uncontrolled hypertension Marked proteinuria (nephrotic syndrome) Arterial thromboemboli or severe haemorrhage within 6 months prior to inclusion in the study (with the exception of tumour bleeding before tumour resection surgery) Haemorrhagic diathesis or tendency towards thrombosis Known DPD deficiency (specific screening not required) Known glucuronidation deficiency (Gilbert's syndrome) (specific screening not required) History of a second malignancy during the past 5 years before inclusion in the study or during participation in the study, with the exception of a dermal basal cell or squamous cell carcinoma or cervical carcinoma in situ, if these were treated curatively. Known history of alcohol or drug abuse A significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study Absent or restricted legal capacity
Studienaktive Standorte
Leopoldina-Krankenhaus der Stadt Schweinfurt GmbH
Medizinische Klinik II
Herr Prof. Dr. Stephan Kanzler
Herr Dr. Michael Brück
Onkologische Schwerpunktpraxis Dr. med. Rudolf Schlag / Dr. med. Björn Schöttker
Herr Dr. Rudolf Schlag
Herr Dr. Joachim Haas
Praxis Dr. Welslau
Herr Dr. Manfred Welslau
REGIOMED Kliniken, Klinikum Coburg
Hämatologie und Onkologie
Herr PD Dr. Christof Lamberti
Universitätsklinikum Würzburg
97080 Würzburg
Medizinische Klinik II, Schwerpunkt Hämatologie/Onkologie
Herr Prof. Dr. med. Volker Kunzmann
Frau Dr. Claudia Löffler