The goal of this clinical trial is to learn if the application of the chemotherapy FOLFIRI and cetuximab works better when given with scheduled breaks or continuously in adults with metastatic colorectal cancer. The main question it aims to answer is, whether worsening of disease after 12 months of treatment is lower when the treatment is given with breaks or given continuously. It will also answer the question whether the quality of life is better and side effects are less if chemotherapy is given with breaks.
Additionally, the treatment breaks will be controlled by blood tests and imaging examinations. A novel blood test will be introduced to investigate, whether worsening of the disease might be detected before the imaging, and whether a quicker reaction by re-starting the therapy would help the patients.
Participants will:
* receive an established chemotherapy mit FOLFIRI and cetuximab * Receive blood tests every 4 weeks and imaging investigations every 12 weeks * fill out questionnaires to report their quality of life
Patient's signed informed consent
Histologically confirmed, UICC stage IV unresectable adenocarcinoma of the colon or rectum
Locally confirmed RAS/BRAF wild-type tumor status (KRAS and NRAS exon 2, 3, 4, BRAF exon 11/15)
Centrally confirmed RAS/BRAF wild-type status by liquid biopsy during screening phase
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.
Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before written informed consent.
New York Heart Association Class III or greater heart failure by clinical judgement.
Myocardial infarction, balloon angioplasty (PTCA) with or without stenting, and cerebral vascular accident/stroke within the past 12 months before randomization
Parallel
FOLFIRI+cetuximab
DrugCetuximab 500 mg/m², 90 min IV infusion on d1; Irinotecan: 180 mg/m², 90-120 min IV infusion on d1; Folinic acid: 400mg/m², 1-2h IV Infusion on d1; 5-FU: 2400 mg/m², 46 h IV infusion on d1. Cycles are repeated on day 15.
Guardant360 ctDNA assay
Diagnostic testDetermination of circulating tumor DNA (ctDNA) in the peripheral blood, part 1: retrospective threshold determination to predict radiological disease progression in Arm 2; part 2: prospective validation of the in part 1 identified ctDNA threshold to guide the scheduled treatment breaks and treatment in Arm 2
Progression-free survival (PFS) on treatment rate at 12 months
Percentage of patients who did not experience disease progression or death, whichever occurs first, while receiving active treatment for 12 months starting from randomization.
PFS1 to PFSN
Each PFS from treatment start with FOLFIRI+cetuximab to the first disease progression in the respective treatment period
Overall survival (OS)
Time from randomization to the date of death by any cause
Objective Response Rate (ORR)
Radiological objective response as determined by RECIST 1.1 criteria
Dynamics of the tumor markers CEA and CA19-9
Translational research
DNA, mRNA and protein expression derived from FFPE tumor tissue and longitudinal blood samples, role of molecular hyperselection on treatment efficacy, integration of digital pathology using digitalized stained tumor tissue sections
Click on the lead sponsor to view all of their trials.
Charite University, Berlin, Germany
Lead sponsor
Guardant Health, Inc.
Collaborator
Merck KGaA, Darmstadt, Germany
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
