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

2026년 7월 15일 업데이트: 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.

연구 개요

상태

모병

정황

개입 / 치료

다른: Longitudinal translational sampling

상세 설명

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.

연구 유형

관찰

등록 (추정된)

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

이름: Krista Zackel
전화번호: +41313899191
이메일: trials@swisscancerinstitute.ch

연구 장소

스위스
- - Aarau, 스위스, CH-5000
    - 모병
    - Kantonsspital Aarau
    - 연락하다:
      
      Peter Moosmann, MD et phil.
      
      전화번호: +41 62 838 60 53
      
      이메일: peter.moosmann@ksa.ch
    - 수석 연구원:
      
      Peter Moosmann, MD et phil.
  - Baden, 스위스, 5404
    - 모병
    - Kantonsspital Baden
    - 연락하다:
      
      Stefanie Pederiva, MD
      
      전화번호: +41 56 486 34 11
      
      이메일: stefanie.pederiva@ksb.ch
    - 수석 연구원:
      
      Stefanie Pederiva, MD
  - Basel, 스위스, 4058
    - 모병
    - St. Claraspital
    - 연락하다:
      
      Melanie Löffler-Baumann, MD
      
      전화번호: +41 61 685 85 85
      
      이메일: melanie.loeffler-baumann@claraspital.ch
    - 수석 연구원:
      
      Melanie Löffler-Baumann, MD
  - Basel, 스위스, CH-4031
    - 모병
    - Universitaetsspital Basel
    - 연락하다:
      
      Viviane Hess, MD
      
      전화번호: +41 61 265 50 59
      
      이메일: viviane.hess@usb.ch
    - 수석 연구원:
      
      Viviane Prof Hess
  - Bern, 스위스, 3010
    - 모병
    - Inselspital Bern
    - 연락하다:
      
      Martin D. Berger, Prof
      
      전화번호: +41 31 632 41 14
      
      이메일: martin.berger@insel.ch
    - 수석 연구원:
      
      Martin Berger, Prof
  - Biel, 스위스, 2502
    - 모병
    - Spitalzentrum Biel - MEDIN La Tour
    - 연락하다:
      
      Emanuel Bührer, MD
      
      전화번호: +41 32 324 39 60
      
      이메일: emanuel.buehrer@szb-chb.ch
    - 수석 연구원:
      
      Emanuel Bührer, MD
  - Chur, 스위스, 7000
    - 모병
    - Kantonsspital Graubunden
    - 수석 연구원:
      
      Sara Bastian, MD
    - 연락하다:
      
      Sara Bastian, MD
      
      전화번호: +41 81 256 66 46
      
      이메일: sara.bastian@ksgr.ch
  - Lucerne, 스위스, 6004
    - 모병
    - Luzerner Kantonsspital
    - 수석 연구원:
      
      Simon Häfliger, MD
    - 연락하다:
      
      Simon Häfliger, MD
      
      전화번호: +41 41 926 58 98
      
      이메일: simon.haefliger.1@luks.ch
  - Sankt Gallen, 스위스, 9007
    - 모병
    - HOCH Health Ostschweiz - Kantonsspital St. Gallen
    - 연락하다:
      
      Barbara Denecke, MD
      
      전화번호: +41 71 494 11 11
      
      이메일: barbara.denecke@h-och.ch
    - 수석 연구원:
      
      Barbara Denecke, MD
  - Solothurn, 스위스, 4500
    - 모병
    - Bürgerspital Solothurn
    - 연락하다:
      
      Julian Schardt, MD et phil.
      
      전화번호: +41 32 627 47 26
      
      이메일: julian.schardt@spital.so.ch
    - 수석 연구원:
      
      Julian Schardt, MD et phil.
  - Villars-sur-Glâne, 스위스, 1752
    - 모병
    - HFR Freiburg - Kantonsspital
    - 연락하다:
      
      Rahel Odermatt, MD
      
      전화번호: +41 26 306 22 60
      
      이메일: rahel.odermatt@h-fr.ch
    - 수석 연구원:
      
      Rahel Odermatt, MD
  - Winterthur, 스위스, 8004
    - 모병
    - Kantonsspital Winterthur
    - 연락하다:
      
      Guacimara Ortega Sanchez, MD
      
      전화번호: +41 52 266 25 43
      
      이메일: guacimara.ortegasanchez@ksw.ch
    - 수석 연구원:
      
      Guacimara Ortega Sanchez, MD
  - Zurich, 스위스, 8091
    - 모병
    - Universitätsspital Zürich USZ
    - 수석 연구원:
      
      Ralph Fritsch, MD
    - 연락하다:
      
      Ralph Fritsch, MD
      
      전화번호: +41 44 255 48 74
      
      이메일: ralph.fritsch@usz.ch

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

성인
고령자

건강한 자원 봉사자를 받아들입니다

아니

샘플링 방법

비확률 샘플

연구 인구

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.

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

그룹/코호트 수

코호트 및 개입

그룹/코호트	개입 / 치료
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.	다른: Longitudinal translational sampling Longitudinal translational sampling (tumor tissue, plasma ctDNA, stool, PBMCs).

그룹/코호트

개입 / 치료

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.

다른: Longitudinal translational sampling

Longitudinal translational sampling (tumor tissue, plasma ctDNA, stool, PBMCs).

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정	측정값 설명	기간
Detection rate of molecular alterations associated with acquired resistance 기간: 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)

2차 결과 측정

결과 측정	측정값 설명	기간
Detection rate of targetable resistance alterations 기간: 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 기간: 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 기간: 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) 기간: 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) 기간: 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 기간: 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)

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Swiss Cancer Institute

수사관

연구 의자: Ralph Fritsch, MD, University of Zurich

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2025년 5월 25일

기본 완료 (추정된)

2030년 9월 1일

연구 완료 (추정된)

2030년 9월 1일

연구 등록 날짜

최초 제출

2026년 5월 22일

QC 기준을 충족하는 최초 제출

2026년 5월 22일

처음 게시됨 (실제)

2026년 6월 1일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 7월 16일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 7월 15일

마지막으로 확인됨

2026년 7월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

SAKK 41/23

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

IPD 계획 설명

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.

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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