metastatic colorectal cancer MedDRA version: 20.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Sponsors
Klinikum der Universität München, Anstalt des öffentlichen Rechts vertreten durch den Vorstand
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Female and male patients can be included in the trial when all following inclusion criteria are met: - patient's informed consent in written form - histologically confirmed metastatic colorectal cancer - metastases are not resectable or the patient can not or does not wish to undergo surgical treatment - no prior chemotherapy of the metastatic disease - measurable metastases according to RECIST version 1.1 (CT Thorax/Abdomen within 4 weeks before registration) - age = 18 years - ECOG performance status 0-1 - Life expectancy > 3 months - Evaluation of the KRAS status (decentralized conduction, result is no requirement at time of inclusion) - patient agrees to asservation of tumor material for the purpose of molecular analyses including determination of the genetic profile of the tumor - time interval to prior adjuvant chemotherapies > 6 months - time interval to prior major surgical interventions, open biopsies or significant traumatic damages = 28 days, to port implantations or minor surgical interventions = 7 days, for placement of CVL = 2 days - women of child bearing potential have to apply adequate contraceptive methods - exclusion of an existing pregnancy - normal cardiac function (LVEF = 55%) confirmed by ECG and echocardiography - patients who do not receive anticoagulation, have to have an INR value =65 years) yes F.1.3.1 Number of
Exclusion criteria
Exclusion criteria: A patient can not be included in the trial, if one of the following criteria is met: - Primarily resectable metastases and patient’s wish to undergo surgical intervention - Heart insufficiency grade III or IV (functional NYHA classification) - Existing concomitant disease or condition, which classifies the patient unsuitable for the trial or would interfere with the patient’s safety - Myocardial infarction, instable angina pectoris, cardiac angioplasty or stent placement within the last 6 months - History of an arterial thromboembolism including stroke, transient ischemic attack or cerebrovascular disease within the last 6 months - Severe bleeding within the last 6 months (excluding tumor bleeding before resection), coagulopathy or bleeding diathesis - Abdominal or tracheo-oesophageal fistulas, gastrointestinal perforations within the last 6 months prior to enrolment into the study - not adequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and /or >100 mmHg diastolic blood pressure) under antihypertensive therapy - History of recurring thromboembolic events (> 1 episode of deep vein thrombosis, peripherally embolism) during the last 2 years - Severe wound healing impairment or ulcerations or bone fractures - Pregnant or lactating patients - any psychological, family related, sociological or geographic occurrence, which does not allow compliance to the study protocol - Additional cancer therapy (chemotherapy, radiation, biological therapy, immunotherapy or hormonal therapy) during the course of the trial - Concomitant treatment with other trial medication, any other explicitly prohibited medication during the course of the trial or participation in another clinical trial - Contraindications for treatment with irinotecan and/or FUFA - Any known immediate or delayed hypersensitivity reaction or idiosyncrasy to pharmaceuticals chemically related to Capecitabine, 5-fluorouracil, folinic acid, Irinotecan or Bevacizumab - Acute or subacute ileus or chronic inflammatory bowel disease - Known glucuronidation defect (Gilbert-Meulengracht-Syndrome) - Untreated brain metastases - Known secondary malignant neoplasm within the last 5 years (excluding basal cell carcinoma or in situ carcinoma of the cervix) - known alcohol or drug abuse - missing or limited legal capacity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluation of effectiveness in correlation to tolerability of both therapy schemes in patients with metastatic colorectal cancer without Prior therapy.; Secondary Objective: - Evaluation of the effect of the study treatment on overall response rate, overall survival, quality of life and PFS1 in both treatment arms - Evaluation of safety and tolerability of both treatment regimes ;Timepoint(s) of evaluation of this end point: - every 9 weeks while on study treatment; Primary end point(s): - Time to failure of treatment strategy (TFS) - If a comparable TFS is reached in both treatment arms, an analysis of the adverse effects should help to define the superior treatment strategy. Treatment related toxicity will be evaluated by analysis of all grade 2-5 toxicities divided by the number of administered treatment cycles within the TFS time intervall | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - overall response rate (ORR) (decentralised recording by the sites) - overall survival (OS) in both Treatment arms, inclusive of 60 days mortality - PFS-1 in both treatment arms (decentralised recording by the sites) - safety and tolerability of both treatment regimens (nature, frequency and relatedness of adveres events and study treatment according to NCI-CTCAE version 4.0) - evaluation of effectiveness and safety depending on the choice of the fluoropyrimidine - analysis of patients age and comorbidities (Charlson-Score) with regard to effectiveness and safety - Analysis of clinical risk factors (for Example GERCOR, FIRE, Köhne) in the study Population - early surrogat marker of the Long term survival: early Tumor shrinkage after 9 week= ETS, depth of Response (recording by the sites) - quality of life (EORTC-QLQ C30) in course of the study - ORR, PFS, TFS, DpR, ETS (central Review of the CT-Staging), also volumetrically - analysis of the effect of molecular factors on outcome parameters, e.g. ORR, PFS, TFS, OS with respect to EGFR and VGFR pathways. Translational research on tumor samles (immunohistochemistry, protein and gene expression) and blood samples (tumor marker, angiogenesis marker, single nucleotide polymorphisms) ; Timepoint(s) of evaluation of this end point: - every 9 weeks while on study treatment - every 3 month while in follow up phase | — |
Countries
Germany
Outcome results
None listed