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

15 de julho de 2026 atualizado por: 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.

Visão geral do estudo

Status

Recrutamento

Condições

Intervenção / Tratamento

Descrição detalhada

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 de estudo

Observacional

Inscrição (Estimado)

30

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Contato de estudo

Locais de estudo

  • Suíça
      • Aarau, Suíça, CH-5000
        • Recrutamento
        • Kantonsspital Aarau
        • Contato:
        • Investigador principal:
          • Peter Moosmann, MD et phil.
      • Baden, Suíça, 5404
        • Recrutamento
        • Kantonsspital Baden
        • Contato:
        • Investigador principal:
          • Stefanie Pederiva, MD
      • Basel, Suíça, 4058
        • Recrutamento
        • St. Claraspital
        • Contato:
        • Investigador principal:
          • Melanie Löffler-Baumann, MD
      • Basel, Suíça, CH-4031
        • Recrutamento
        • Universitaetsspital Basel
        • Contato:
        • Investigador principal:
          • Viviane Prof Hess
      • Bern, Suíça, 3010
        • Recrutamento
        • Inselspital Bern
        • Contato:
        • Investigador principal:
          • Martin Berger, Prof
      • Biel, Suíça, 2502
        • Recrutamento
        • Spitalzentrum Biel - MEDIN La Tour
        • Contato:
        • Investigador principal:
          • Emanuel Bührer, MD
      • Chur, Suíça, 7000
        • Recrutamento
        • Kantonsspital Graubunden
        • Investigador principal:
          • Sara Bastian, MD
        • Contato:
      • Lucerne, Suíça, 6004
        • Recrutamento
        • Luzerner Kantonsspital
        • Investigador principal:
          • Simon Häfliger, MD
        • Contato:
      • Sankt Gallen, Suíça, 9007
        • Recrutamento
        • HOCH Health Ostschweiz - Kantonsspital St. Gallen
        • Contato:
        • Investigador principal:
          • Barbara Denecke, MD
      • Solothurn, Suíça, 4500
        • Recrutamento
        • Bürgerspital Solothurn
        • Contato:
        • Investigador principal:
          • Julian Schardt, MD et phil.
      • Villars-sur-Glâne, Suíça, 1752
        • Recrutamento
        • HFR Freiburg - Kantonsspital
        • Contato:
        • Investigador principal:
          • Rahel Odermatt, MD
      • Winterthur, Suíça, 8004
        • Recrutamento
        • Kantonsspital Winterthur
        • Contato:
        • Investigador principal:
          • Guacimara Ortega Sanchez, MD
      • Zurich, Suíça, 8091
        • Recrutamento
        • Universitätsspital Zürich USZ
        • Investigador principal:
          • Ralph Fritsch, MD
        • Contato:

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

  • Adulto
  • Adulto mais velho

Aceita Voluntários Saudáveis

Não

Método de amostragem

Amostra Não Probabilística

População do estudo

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.

Descrição

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

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

Coortes e Intervenções

Grupo / Coorte
Intervenção / Tratamento
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.
Outro: Longitudinal translational sampling
Longitudinal translational sampling (tumor tissue, plasma ctDNA, stool, PBMCs).

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Detection rate of molecular alterations associated with acquired resistance
Prazo: 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)

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Detection rate of targetable resistance alterations
Prazo: 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
Prazo: 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
Prazo: 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)
Prazo: 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)
Prazo: 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
Prazo: 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)

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Swiss Cancer Institute

Investigadores

  • Cadeira de estudo: Ralph Fritsch, MD, University of Zurich

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

25 de maio de 2025

Conclusão Primária (Estimado)

1 de setembro de 2030

Conclusão do estudo (Estimado)

1 de setembro de 2030

Datas de inscrição no estudo

Enviado pela primeira vez

22 de maio de 2026

Enviado pela primeira vez que atendeu aos critérios de CQ

22 de maio de 2026

Primeira postagem (Real)

1 de junho de 2026

Atualizações de registro de estudo

Última Atualização Postada (Real)

16 de julho de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

15 de julho de 2026

Última verificação

1 de julho de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • SAKK 41/23

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

NÃO

Descrição do plano 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.

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Não

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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