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

Sponsor
Swiss Cancer Institute
Study ID
NCT07617610
Status
Recruiting
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Conditions

  • BRAF V600E Mutation
  • Metastatic Colorectal Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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.

Key Dates

First listed
Jun 1, 2026
Start date
May 25, 2025
Status verified
Jul 2026
Primary completion
Sep 30, 2030
Completion
Sep 30, 2030

Study Design

Enrollment
30 participants (estimated)

Arms

  • Arm: 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.

Primary Outcome Measure

Detection rate of molecular alterations associated with acquired resistance [ Time Frame: from baseline (pre-treatment) to disease progression (approximately 12 months) ]

Central Contacts

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