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

2026年7月15日 更新者：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.

研究概览

地位

招聘中

条件

干预/治疗

详细说明

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.

研究类型

观察性的

注册 (估计的)

30

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

学习地点

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

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

  • 成人
  • 年长者

接受健康志愿者

不

取样方法

非概率样本

研究人群

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.

描述

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

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

队列和干预

团体/队列
干预/治疗
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.
其他：Longitudinal translational sampling
Longitudinal translational sampling (tumor tissue, plasma ctDNA, stool, PBMCs).

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Detection rate of molecular alterations associated with acquired resistance
大体时间：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)

次要结果测量

结果测量
措施说明
大体时间
Detection rate of targetable resistance alterations
大体时间：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
大体时间：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
大体时间：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)
大体时间：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)
大体时间：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
大体时间：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)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Swiss Cancer Institute

调查人员

  • 学习椅：Ralph Fritsch, MD、University of Zurich

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2025年5月25日

初级完成 (估计的)

2030年9月1日

研究完成 (估计的)

2030年9月1日

研究注册日期

首次提交

2026年5月22日

首先提交符合 QC 标准的

2026年5月22日

首次发布 (实际的)

2026年6月1日

研究记录更新

最后更新发布 (实际的)

2026年7月16日

上次提交的符合 QC 标准的更新

2026年7月15日

最后验证

2026年7月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • SAKK 41/23

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

IPD 计划说明

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.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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