Metastatic Colorectal CancerPARTACERNCT07617610
Primary and Acquired Resistance to Targeted Treatment in BRAF V600E-mutated Metastatic Colorectal Cancer
An observational study of Metastatic Colorectal Cancer and BRAF V600E Mutation, run by Swiss Cancer Institute at 13 sites in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer, BRAF V600E Mutation
- What is being tested?
- Longitudinal translational sampling
- How many people
- 30 participants
- Where
- 13 sitesSwitzerland
- Study dates
- 25 May 2025to Sep 2030
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
13 sites in 1 country
Switzerland13 sites, 13 recruiting
- Recruiting
Kantonsspital Aarau
Aarau, CH-5000
Peter Moosmann, MD et phil., +41 62 838 60 53, peter.moosmann@ksa.ch
Peter Moosmann, MD et phil.
- Recruiting
Kantonsspital Baden
Baden, 5404
Stefanie Pederiva, MD, +41 56 486 34 11, stefanie.pederiva@ksb.ch
Stefanie Pederiva, MD
- Recruiting
St. Claraspital
Basel, 4058
Melanie Löffler-Baumann, MD, +41 61 685 85 85, melanie.loeffler-baumann@claraspital.ch
Melanie Löffler-Baumann, MD
- Recruiting
Universitaetsspital Basel
Basel, CH-4031
Viviane Hess, MD, +41 61 265 50 59, viviane.hess@usb.ch
Viviane Prof Hess
- Recruiting
Inselspital Bern
Bern, 3010
Martin D. Berger, Prof, +41 31 632 41 14, martin.berger@insel.ch
Martin Berger, Prof
- Recruiting
Spitalzentrum Biel - MEDIN La Tour
Biel, 2502
Emanuel Bührer, MD, +41 32 324 39 60, emanuel.buehrer@szb-chb.ch
Emanuel Bührer, MD
- Recruiting
Kantonsspital Graubünden
Chur, 7000
Sara Bastian, MD, +41 81 256 66 46, sara.bastian@ksgr.ch
Sara Bastian, MD
- Recruiting
Luzerner Kantonsspital
Lucerne, 6004
Simon Häfliger, MD, +41 41 926 58 98, simon.haefliger.1@luks.ch
Simon Häfliger, MD
- Recruiting
HOCH Health Ostschweiz - Kantonsspital St. Gallen
Sankt Gallen, 9007
Barbara Denecke, MD, +41 71 494 11 11, barbara.denecke@h-och.ch
Barbara Denecke, MD
- Recruiting
Bürgerspital Solothurn
Solothurn, 4500
Julian Schardt, MD et phil., +41 32 627 47 26, julian.schardt@spital.so.ch
Julian Schardt, MD et phil.
- Recruiting
HFR Freiburg - Kantonsspital
Villars-sur-Glâne, 1752
Rahel Odermatt, MD, +41 26 306 22 60, rahel.odermatt@h-fr.ch
Rahel Odermatt, MD
- Recruiting
Kantonsspital Winterthur
Winterthur, 8004
Guacimara Ortega Sanchez, MD, +41 52 266 25 43, guacimara.ortegasanchez@ksw.ch
Guacimara Ortega Sanchez, MD
- Recruiting
Universitätsspital Zürich USZ
Zurich, 8091
Ralph Fritsch, MD, +41 44 255 48 74, ralph.fritsch@usz.ch
Ralph Fritsch, MD
About this study
Official title: Primary and Acquired Resistance to Targeted Treatment in BRAF V600E-mutated Metastatic Colorectal Cancer (PARTACER-Suisse)
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.
Read the detailed description
BRAF V600E-mutated metastatic colorectal cancer accounts for about 8-10% of cases and is an aggressive disease with poor prognosis and limited treatment options. The current standard treatment for patients is the combination of the BRAF inhibitor encorafenib and the anti-EGFR antibody cetuximab, together with FOLFOX or FOLFIRI chemotherapy in 1st line systemic treatment, which improves survival and response rates compared to chemotherapy alone. However, nearly all patients eventually develop resistance to this treatment, and there are no well-established therapies after progression. Resistance develops through complex and often multiple mechanisms, including genetic changes in signaling pathways such as MAPK and receptor tyrosine kinases, as well as non-genomic factors such as changes in gene expression, the tumor microenvironment, and potentially the microbiome. These mechanisms are not yet fully understood, especially in combination and over time during treatment.
This study, PARTACER-Suisse, is a prospective multicenter investigator-initiated study in patients with BRAF V600E-mutated metastatic colorectal cancer receiving standard treatment with encorafenib and cetuximab, with or without concomitant chemotherapy. The study is conducted across a federated network of Swiss oncology centers organized under the Swiss Cancer Center/Swiss Group for Clinical Cancer Research (SCI/SAKK), with a central translational research backbone at the University Hospital Zurich. The aim is to better understand how resistance develops by analyzing tumor samples, blood samples, and stool samples collected before treatment and at disease progression. Blood samples will be used to study circulating tumor DNA over time, and stool samples will allow analysis of the microbiome. Tumor tissue will undergo detailed molecular analyses to identify genetic and non-genetic changes associated with resistance. In addition, tumor samples will be used to generate patient-derived organoids, which are laboratory models that allow functional testing of tumor behavior and response to treatment. By combining molecular analyses with functional experiments, the study aims to identify key resistance mechanisms and explore new treatment strategies that could prevent or overcome resistance.
Overall, this study is expected to provide a more complete understanding of resistance to combined BRAF and EGFR inhibition in this patient population and to support the development of improved and more personalized treatment approaches for the future.
- Conditions
- Metastatic Colorectal Cancer, BRAF V600E Mutation
- Being tested
- Longitudinal translational sampling
- Keywords
- Metastatic Colorectal Cancer, mCRC, BRAF V600E, Targeted therapy resistance, Encorafenib, Cetuximab, EGFR inhibition, BRAF inhibition, Liquid biopsy, Precision oncology, Patient-derived organoids, Circulating tumor DNA, ctDNA, Microbiome, Comprehensive genomic profiling, SCI/SAKK
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Longitudinal translational samplingOther
Longitudinal translational sampling (tumor tissue, plasma ctDNA, stool, PBMCs).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Longitudinal translational sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: from baseline (pre-treatment) to disease progression (approximately 12 months)
Secondary outcomes (6)
Detection rate of targetable resistance alterations
Proportion of patients with acquired resistance alterations that are potentially targetable by available or investigational therapies, identified through molecular profiling of tissue and liquid biopsy samples.
Measured: Baseline to disease progression (approximately 12 months)
Detection rate of non-genomic resistance mechanisms
Proportion of patients with non-genomic mechanisms of resistance, including transcriptomic changes and tumor microenvironment alterations, identified through molecular analyses.
Measured: Baseline to disease progression (approximately 12 months)
Comparison of resistance alterations in tissue versus liquid biopsies
Concordance and detection rates of resistance-associated molecular alterations in matched tumor tissue and circulating tumor DNA samples.
Measured: Baseline to disease progression (approximately 12 months)
Establishment rate of patient-derived organoids (PDOs)
Proportion of collected tumor biopsies (baseline and progression) from which patient-derived organoid cultures are successfully established for downstream functional analyses.
Measured: From baseline biopsy collection through PDO establishment (approximately 3 to 6 months per sample)
Longitudinal dynamics of circulating tumor DNA (ctDNA)
Quantitative changes in plasma ctDNA tumor fraction and variant allele frequencies of mutations from baseline through on-treatment time points to progression, and their association with radiological response and resistance evolution.
Measured: Baseline, every 8 to 12 weeks during treatment, and at disease progression (up to approximately 24 months)
Compositional characterization of the gut microbiome
Compositional and functional features of the gut microbiome at baseline and at disease progression, and their association with treatment response and resistance.
Measured: Baseline and at disease progression (approximately 12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2026
- Study start25 May 2025
- Primary completionSep 2030 (estimated)
- Study completionSep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Swiss Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ralph Fritsch, MD, Study chair, University of Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07617610
- Sponsor's protocol ID
- SAKK 41/23
- Acronym
- PARTACER
- Status last verified
- Jul 2026
- First submitted
- 22 May 2026
- Last updated
- 16 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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.