Primary and Acquired Resistance to Targeted Treatment in BRAF V600E-mutated Metastatic Colorectal Cancer
Recruiting · NCT07617610 · Observational (researchers observe without assigning treatment) · Lead sponsor: Swiss Cancer Institute
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
This study prospectively investigates the molecular mechanisms of primary and acquired resistance to standard-of-care BRAF V600E-directed therapy in patients with metastatic colorectal cancer and aims to pre-clinically develop novel strategies to reverse therapy resistance. Clinically approved combination treatment with cetuximab, encorafenib and chemotherapy improves patient outcomes, yet patients eventually experience disease progression. In this prospective multicenter study, tumor tissue, blood, and stool samples will be collected before treatment and at progression, to identify genetic and non-genetic mechanisms of resistance. Additionally, tumor tissue-based in vitro models (patient-derived organoids, PDOs) will be generated and exploited for functional in vitro testing, including genomic and pharmacologic perturbation studies. The overarching goal is to generate knowledge that can help develop new and more effective treatment strategies for future patients.
Who can take part
Inclusion criteria
- Diagnosis of unresectable or metastatic BRAF V600E-mutated colorectal cancer
- Planned initiation of treatment with combined anti-EGFR antibody and BRAF inhibitor
- Patients receiving treatment in any line, with or without chemotherapy
- At least one tumor lesion accessible for biopsy
- ECOG performance status 0-2
- Life expectancy of at least 3 months
- Age ≥18 years
- Ability to provide written informed consent
Exclusion criteria
- Medical or surgical contraindication for tumor biopsy
- Active second malignancy (except non-melanoma skin cancer)
- Inability to comply with study procedures (e.g., due to language barriers or cognitive impairment)
- Pregnancy or breastfeeding
- Previous treatment with a BRAF inhibitor
Where it is running
13 locations listed.
- Kantonsspital Aarau - Aarau, Switzerland
- Kantonsspital Baden - Baden, Switzerland
- St. Claraspital - Basel, Switzerland
- Universitaetsspital Basel - Basel, Switzerland
- Inselspital Bern - Bern, Switzerland
- Spitalzentrum Biel - MEDIN La Tour - Biel, Switzerland
- Kantonsspital Graubünden - Chur, Switzerland
- Luzerner Kantonsspital - Lucerne, Switzerland
- HOCH Health Ostschweiz - Kantonsspital St. Gallen - Sankt Gallen, Switzerland
- Bürgerspital Solothurn - Solothurn, Switzerland
- HFR Freiburg - Kantonsspital - Villars-sur-Glâne, Switzerland
- Kantonsspital Winterthur - Winterthur, Switzerland
- Universitätsspital Zürich USZ - Zurich, Switzerland