Primary and Acquired Resistance to Targeted Treatment in BRAF V600E-mutated Metastatic Colorectal Cancer
PARTACER
1 other identifier
observational
30
1 country
13
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for all trials
Started May 2025
Longer than P75 for all trials
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 25, 2025
CompletedFirst Submitted
Initial submission to the registry
May 22, 2026
CompletedFirst Posted
Study publicly available on registry
June 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2030
July 16, 2026
July 1, 2026
5.3 years
May 22, 2026
July 15, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Detection rate of molecular alterations associated with acquired resistance
Proportion of patients with detectable molecular alterations associated with acquired resistance to combined BRAF and EGFR inhibition, identified in tumor tissue collected before treatment and at disease progression using molecular profiling.
from baseline (pre-treatment) to disease progression (approximately 12 months)
Secondary Outcomes (6)
Detection rate of targetable resistance alterations
Baseline to disease progression (approximately 12 months)
Detection rate of non-genomic resistance mechanisms
Baseline to disease progression (approximately 12 months)
Comparison of resistance alterations in tissue versus liquid biopsies
Baseline to disease progression (approximately 12 months)
Establishment rate of patient-derived organoids (PDOs)
From baseline biopsy collection through PDO establishment (approximately 3 to 6 months per sample)
Longitudinal dynamics of circulating tumor DNA (ctDNA)
Baseline, every 8 to 12 weeks during treatment, and at disease progression (up to approximately 24 months)
- +1 more secondary outcomes
Study Arms (1)
Patients with BRAF V600E-mutated metastatic colorectal cancer
Patients with unresectable or metastatic BRAF V600E-mutated colorectal cancer receiving standard-of-care treatment with combined BRAF and EGFR inhibition (e.g., encorafenib and cetuximab), with or without concomitant chemotherapy. Participants are enrolled prior to treatment initiation and followed longitudinally with collection of tumor tissue, blood, and stool samples to study mechanisms of treatment resistance.
Interventions
Longitudinal translational sampling (tumor tissue, plasma ctDNA, stool, PBMCs).
Eligibility Criteria
Participants will be recruited from oncology centers across Switzerland participating in the Swiss Group for Clinical Cancer Research (SAKK). The study population consists of adult patients with metastatic colorectal cancer treated in routine clinical practice at tertiary care and regional cancer centers. Eligible patients are identified by their treating oncologists at participating sites and enrolled prior to initiation of standard-of-care systemic therapy. Recruitment is limited to centers with access to molecular diagnostics and the capability to perform tumor biopsies and longitudinal sample collection.
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
Kantonsspital Aarau
Aarau, CH-5000, Switzerland
Kantonsspital Baden
Baden, 5404, Switzerland
St. Claraspital
Basel, 4058, Switzerland
Universitaetsspital Basel
Basel, CH-4031, Switzerland
Inselspital Bern
Bern, 3010, Switzerland
Spitalzentrum Biel - MEDIN La Tour
Biel, 2502, Switzerland
Kantonsspital Graubünden
Chur, 7000, Switzerland
Luzerner Kantonsspital
Lucerne, 6004, Switzerland
HOCH Health Ostschweiz - Kantonsspital St. Gallen
Sankt Gallen, 9007, Switzerland
Bürgerspital Solothurn
Solothurn, 4500, Switzerland
HFR Freiburg - Kantonsspital
Villars-sur-Glâne, 1752, Switzerland
Kantonsspital Winterthur
Winterthur, 8004, Switzerland
Universitätsspital Zürich USZ
Zurich, 8091, Switzerland
Biospecimen
Tumor tissue biopsies (fresh and FFPE), whole blood, plasma for circulating tumor DNA (ctDNA), peripheral blood mononuclear cells (PBMCs), and stool samples for microbiome analyses will be collected and stored. Tumor tissue is processed for DNA and RNA extraction, histology, and organoid generation. Blood samples are processed for plasma and PBMC isolation. Tissue and plasma samples undergo central comprehensive genomic profiling (FoundationOne CDx and FoundationOne Liquid CDx). All biospecimens are coded and stored under controlled conditions for molecular and functional analyses.
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Ralph Fritsch, MD
University of Zurich
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 22, 2026
First Posted
June 1, 2026
Study Start
May 25, 2025
Primary Completion (Estimated)
September 1, 2030
Study Completion (Estimated)
September 1, 2030
Last Updated
July 16, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will not share
This is a non-interventional observational study with translational research components. Individual participant data sharing is not planned. Aggregate study results, including de-identified molecular and clinical data summaries, will be disseminated through peer-reviewed publications and scientific meetings. De-identified data may be shared with collaborators on a case-by-case basis upon reasonable request to the Study Chair and subject to applicable Swiss data protection regulations, institutional review, and a data-transfer agreement.