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Primary and Acquired Resistance to Targeted Treatment in BRAF V600E-mutated Metastatic Colorectal Cancer (PARTACER)

22 maggio 2026 aggiornato da: Swiss Cancer Institute

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.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Osservativo

Iscrizione (Stimato)

30

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Luoghi di studio

  • Svizzera
      • Aarau, Svizzera, CH-5000
        • Reclutamento
        • Kantonsspital Aarau
        • Contatto:
        • Investigatore principale:
          • Peter Moosmann, MD et phil.
      • Baden, Svizzera, 5404
        • Reclutamento
        • Kantonsspital Baden
        • Contatto:
        • Investigatore principale:
          • Stefanie Pederiva, MD
      • Basel, Svizzera, 4058
        • Reclutamento
        • St. Claraspital
        • Contatto:
        • Investigatore principale:
          • Melanie Löffler-Baumann, MD
      • Basel, Svizzera, CH-4031
        • Reclutamento
        • Universitaetsspital Basel
        • Contatto:
        • Investigatore principale:
          • Viviane Prof Hess
      • Bern, Svizzera, 3010
        • Reclutamento
        • Inselspital Bern
        • Contatto:
        • Investigatore principale:
          • Martin Berger, Prof
      • Chur, Svizzera, 7000
        • Reclutamento
        • Kantonsspital Graubunden
        • Investigatore principale:
          • Sara Bastian, MD
        • Contatto:
      • Lucerne, Svizzera, 6004
        • Reclutamento
        • Luzerner Kantonsspital
        • Investigatore principale:
          • Simon Häfliger, MD
        • Contatto:
      • Sankt Gallen, Svizzera, 9007
        • Reclutamento
        • HOCH Health Ostschweiz - Kantonsspital St. Gallen
        • Contatto:
        • Investigatore principale:
          • Barbara Denecke, MD
      • Solothurn, Svizzera, 4500
        • Reclutamento
        • Bürgerspital Solothurn
        • Contatto:
        • Investigatore principale:
          • Julian Schardt, MD et phil.
      • Villars-sur-Glâne, Svizzera, 1752
        • Reclutamento
        • HFR Freiburg - Kantonsspital
        • Contatto:
        • Investigatore principale:
          • Rahel Odermatt, MD
      • Winterthur, Svizzera, 8004
        • Reclutamento
        • Kantonsspital Winterthur
        • Contatto:
        • Investigatore principale:
          • Guacimara Ortega Sanchez, MD
      • Zurich, Svizzera, 8091
        • Reclutamento
        • Universitätsspital Zürich USZ
        • Investigatore principale:
          • Ralph Fritsch, MD
        • Contatto:

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Metodo di campionamento

Campione non probabilistico

Popolazione di studio

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.

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

Coorti e interventi

Gruppo / Coorte
Intervento / Trattamento
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.
Altro: Longitudinal translational sampling
Longitudinal translational sampling (tumor tissue, plasma ctDNA, stool, PBMCs).

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Detection rate of molecular alterations associated with acquired resistance
Lasso di tempo: from baseline (pre-treatment) to disease progression (approximately 12 months)
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)

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Detection rate of targetable resistance alterations
Lasso di tempo: Baseline to disease progression (approximately 12 months)
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.
Baseline to disease progression (approximately 12 months)
Detection rate of non-genomic resistance mechanisms
Lasso di tempo: Baseline to disease progression (approximately 12 months)
Proportion of patients with non-genomic mechanisms of resistance, including transcriptomic changes and tumor microenvironment alterations, identified through molecular analyses.
Baseline to disease progression (approximately 12 months)
Comparison of resistance alterations in tissue versus liquid biopsies
Lasso di tempo: Baseline to disease progression (approximately 12 months)
Concordance and detection rates of resistance-associated molecular alterations in matched tumor tissue and circulating tumor DNA samples.
Baseline to disease progression (approximately 12 months)
Establishment rate of patient-derived organoids (PDOs)
Lasso di tempo: From baseline biopsy collection through PDO establishment (approximately 3 to 6 months per sample)
Proportion of collected tumor biopsies (baseline and progression) from which patient-derived organoid cultures are successfully established for downstream functional analyses.
From baseline biopsy collection through PDO establishment (approximately 3 to 6 months per sample)
Longitudinal dynamics of circulating tumor DNA (ctDNA)
Lasso di tempo: Baseline, every 8 to 12 weeks during treatment, and at disease progression (up to approximately 24 months)
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.
Baseline, every 8 to 12 weeks during treatment, and at disease progression (up to approximately 24 months)
Compositional characterization of the gut microbiome
Lasso di tempo: Baseline and at disease progression (approximately 12 months)
Compositional and functional features of the gut microbiome at baseline and at disease progression, and their association with treatment response and resistance.
Baseline and at disease progression (approximately 12 months)

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Swiss Cancer Institute

Investigatori

  • Cattedra di studio: Ralph Fritsch, MD, University of Zurich

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

25 maggio 2025

Completamento primario (Stimato)

1 settembre 2030

Completamento dello studio (Stimato)

1 settembre 2030

Date di iscrizione allo studio

Primo inviato

22 maggio 2026

Primo inviato che soddisfa i criteri di controllo qualità

22 maggio 2026

Primo Inserito (Effettivo)

1 giugno 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

1 giugno 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

22 maggio 2026

Ultimo verificato

1 maggio 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • SAKK 41/23

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Descrizione del piano IPD

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.

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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