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

15 de julio de 2026 actualizado 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.

Descripción general del estudio

Estado

Reclutamiento

Condiciones

Intervención / Tratamiento

Descripción detallada

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 estudio

De observación

Inscripción (Estimado)

30

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Ubicaciones de estudio

  • Suiza
      • Aarau, Suiza, CH-5000
        • Reclutamiento
        • Kantonsspital Aarau
        • Contacto:
          • Peter Moosmann, MD et phil.
          • Número de teléfono: +41 62 838 60 53
          • Correo electrónico: peter.moosmann@ksa.ch
        • Investigador principal:
          • Peter Moosmann, MD et phil.
      • Baden, Suiza, 5404
        • Reclutamiento
        • Kantonsspital Baden
        • Contacto:
        • Investigador principal:
          • Stefanie Pederiva, MD
      • Basel, Suiza, 4058
        • Reclutamiento
        • St. Claraspital
        • Contacto:
        • Investigador principal:
          • Melanie Löffler-Baumann, MD
      • Basel, Suiza, CH-4031
        • Reclutamiento
        • Universitaetsspital Basel
        • Contacto:
          • Viviane Hess, MD
          • Número de teléfono: +41 61 265 50 59
          • Correo electrónico: viviane.hess@usb.ch
        • Investigador principal:
          • Viviane Prof Hess
      • Bern, Suiza, 3010
        • Reclutamiento
        • Inselspital Bern
        • Contacto:
        • Investigador principal:
          • Martin Berger, Prof
      • Biel, Suiza, 2502
        • Reclutamiento
        • Spitalzentrum Biel - MEDIN La Tour
        • Contacto:
        • Investigador principal:
          • Emanuel Bührer, MD
      • Chur, Suiza, 7000
        • Reclutamiento
        • Kantonsspital Graubunden
        • Investigador principal:
          • Sara Bastian, MD
        • Contacto:
      • Lucerne, Suiza, 6004
        • Reclutamiento
        • Luzerner Kantonsspital
        • Investigador principal:
          • Simon Häfliger, MD
        • Contacto:
      • Sankt Gallen, Suiza, 9007
        • Reclutamiento
        • HOCH Health Ostschweiz - Kantonsspital St. Gallen
        • Contacto:
        • Investigador principal:
          • Barbara Denecke, MD
      • Solothurn, Suiza, 4500
        • Reclutamiento
        • Bürgerspital Solothurn
        • Contacto:
        • Investigador principal:
          • Julian Schardt, MD et phil.
      • Villars-sur-Glâne, Suiza, 1752
        • Reclutamiento
        • HFR Freiburg - Kantonsspital
        • Contacto:
        • Investigador principal:
          • Rahel Odermatt, MD
      • Winterthur, Suiza, 8004
        • Reclutamiento
        • Kantonsspital Winterthur
        • Contacto:
        • Investigador principal:
          • Guacimara Ortega Sanchez, MD
      • Zurich, Suiza, 8091
        • Reclutamiento
        • Universitätsspital Zürich USZ
        • Investigador principal:
          • Ralph Fritsch, MD
        • Contacto:
          • Ralph Fritsch, MD
          • Número de teléfono: +41 44 255 48 74
          • Correo electrónico: ralph.fritsch@usz.ch

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Método de muestreo

Muestra no probabilística

Población de estudio

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.

Descripción

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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

Cohortes e Intervenciones

Grupo / Cohorte
Intervención / Tratamiento
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.
Otro: Longitudinal translational sampling
Longitudinal translational sampling (tumor tissue, plasma ctDNA, stool, PBMCs).

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Detection rate of molecular alterations associated with acquired resistance
Periodo de tiempo: 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 resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Detection rate of targetable resistance alterations
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Swiss Cancer Institute

Investigadores

  • Silla de estudio: Ralph Fritsch, MD, University of Zurich

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

25 de mayo de 2025

Finalización primaria (Estimado)

1 de septiembre de 2030

Finalización del estudio (Estimado)

1 de septiembre de 2030

Fechas de registro del estudio

Enviado por primera vez

22 de mayo de 2026

Primero enviado que cumplió con los criterios de control de calidad

22 de mayo de 2026

Publicado por primera vez (Actual)

1 de junio de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

16 de julio de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

15 de julio de 2026

Última verificación

1 de julio de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • SAKK 41/23

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

NO

Descripción del plan 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.

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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