Biomarker Directed Treatment in Metastatic Colorectal Cancer
Metastatic Colorectal Cancer
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring metastatic colorectal cancer, mCRC, ERCC-1, ERCC1, AGMT
Eligibility Criteria
Inclusion Criteria:
1.1 Inclusion criteria for pre-screening phase:
- Untreated advanced metastatic colorectal cancer patients
- Adequate tissue to evaluate for genotyping (10 x 10µm thick formalin fixed paraffin embedded tissue sections and one corresponding HE stained slide or a FFPE tumor block)
1.2 Inclusion criteria for treatment phase:
Patients must fulfill all criteria listed below prior to enrolment in the study:
- Untreated wild-type KRAS metastatic colorectal cancer
- Previous adjuvant therapy must have been completed > 6 months before therapy initiation on this study
- Age >18 years
- Measureable disease with CT or MRI
- ECOG performance status of 0-2
Adequate organ function
Hematologic:
- Absolute neutrophil count > 1,500/µL
- Hemoglobin >9 mg/dl
- Platelet count >100,000 /µl
Renal:
- Serum creatinine <1.5 x Upper limit of normal (UPN) or estimated clearance > 30 ml/min
Hepatic:
- Serum bilirubin < 1.5 mg/dl
Exclusion Criteria:
- Creatinine clearance below 30 ml/min
- Patients with a history of other malignancies within 2 years prior to study entry, except for adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with curative intent.
- Patients with a history of severe cardiac disease; e.g. NYHA Functional Class III or IV heart failure, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, or unstable angina.
- Other known co-morbidity with the potential to dominate survival
- Hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the applied drugs
- Pregnant or breast feeding women
- Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.
Sites / Locations
- KUK Linz - Med Campus III.: Univ.-Klinik für Hämatologie und Internistische Onkologie
- A.ö. Bezirkskrankenhaus Kufstein, Innere Medizin / Hämatologie / Onkologie
- LKH Feldkirch, Interne E
- LKH Bludenz Innere Medizin
- LKH Bregenz
- KH Dornbirn, Innere Medizin
- Universitätsklinikum Graz
- LKH Hohenems, Interne Intensivmedizin
- Krankenhaus d. Barmherzigen Schwestern Linz
- Universitätsklinik für Innere Medizin III mit Hämatologie, internistischer Onkologie, Infektologie, Rheumatologie und Onkologisches Zentrum
- Medizinische Universität Wien, Univ.Klinik für Innere Medizin I, Abteilung für Onkologie
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
ERCC-1 low
ERCC-1 high
modifiedFOLFOX6 + Cetuximab oxaliplatin 85 mg/m2 on day 1, 15 q d29 for 6 cycles folinic acid (FA) 400 mg/m2 on days 1 and 15 and q d29 for 6 cycles fluorouracil (5-FU) 400 mg/m2 bolus day 1 + 2400 mg/m2 46-hour infusion on days 1, 2 and 15, 16 and q d29 for 6 cycles or until unacceptable toxicity Cetuximab will be administered as a 120- minute intravenous infusion at 500 mg/m2 on day 1 then 500 mg/m2 bi-weekly
FOLFIRI + Cetuximab irinotecan 180 mg/m² on day 1, 15 q d29 for 6 cycles folinic acid (FA)400 mg/m2 on days 1 and 15 and q d29 for 6 cycles fluorouracil (5-FU) 400 mg/m2 bolus + 2400 mg/m2 46-hour infusion on days 1, 2 and 15, 16 and q d29 for 6 cycles or until unacceptable toxicity Cetuximab will be administered as a 120- minute intravenous infusion at 500 mg/m2 on day 1 then 500 mg/m2 bi-weekly