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NCT Number: NCT07619859

Impact of Fusobacterium Nucleatum on Response to Anti-EGFR Therapy in Metastatic Colorectal Cancer

This retrospective observational cohort study investigates the association between the intratumoral burden of the bacterium Fusobacterium nucleatum (Fn) and the efficacy of anti-EGFR targeted therapies (cetuximab or panitumumab) in patients with RAS wild-type metastatic colorectal cancer (mCRC). Bacterial quantification will be performed using droplet digital polymerase chain reaction (ddPCR) on formalin-fixed, paraffin-embedded (FFPE) tissue samples, comprising an estimated cohort of 500 patients.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Metastatic Colorectal Cancer (CRC) Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Barretos Cancer Hospital

Barretos, São Paulo, 14784-400, Brazil

About this study

RAS wild-type colorectal cancer is frequently treated with anti-EGFR monoclonal antibodies; however, primary and acquired resistance rates remain a major limitation to clinical outcomes. Recent evidence suggests that Fusobacterium nucleatum colonization acts as a resistance factor to conventional chemotherapy through the induction of autophagy. This project aims to address the current scientific gap regarding the impact of this bacterium on the response to EGFR inhibitors. The study includes absolute quantification of bacterial 16S ribosomal RNA by droplet digital polymerase chain reaction (ddPCR) and its association with clinicopathological variables, overall survival, progression-free survival, and molecular profile (BRAF, TP53, PIK3CA, and MSI). Additionally, in an exploratory approach, the study will perform a comparative investigation of microbial colonization dynamics between primary tumor sites and their corresponding metastatic lesions using paired tissue samples.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histologically confirmed diagnosis of metastatic (Stage IV) adenocarcinoma of the colon or rectum.
  • Received at least one cycle of anti-EGFR therapy (cetuximab or panitumumab), either as monotherapy or in combination regimens, regardless of the line of therapy.
  • Anti-EGFR therapy administered between January 2016 and December 2022.
  • Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks (from primary tumor or metastatic site) stored in the institutional biobank, with adequate quality for molecular analysis

Exclusion criteria

  • Primary tumor originating in sites other than the colon or rectum.
  • Presence of activating mutations in KRAS or NRAS genes.
  • Presence of BRAF gene mutation (except for patients who received anti-EGFR therapy combined with BRAF inhibitors, according to standard clinical practice for this subgroup).
  • Tumor histology other than adenocarcinoma.
  • Insufficient clinical or follow-up data in medical records for the evaluation of the study's primary endpoints

Treatment and study plan

Primary outcomes

  1. Objective Response Rate (ORR)

    Time frame: From the date of first anti-EGFR administration until disease progression, assessed up to 186 months

    Proportion of patients who achieved complete or partial response as assessed according to standardized RECIST 1.1 criteria.

  2. Overall Survival (OS)

    Time frame: From the date of initial anti-EGFR therapy administration to the date of death from any cause, with a maximum follow-up assessment of up to 186 months.

    Time elapsed from diagnosis to death from any cause

  3. Progression-Free Survival (PFS).

    Time frame: From the date of initial anti-EGFR therapy administration to the date of first documented radiological disease progression, with a maximum follow-up assessment of up to 186 months

    Time elapsed from treatment initiation (for each line of therapy) to radiological disease progression or death.

Secondary outcomes

  1. F. nucleatum Load by Tumor Topography and Paired Metastases, Assessed by ddPCR

    Time frame: Up to 186 months.

    Analyses will be stratified according to the location of the primary tumor (right-sided colon, left-sided colon, and rectum). In paired samples, the Fusobacterium nucleatum burden will be compared between biopsies from the primary tumor and the corresponding metastatic lesion.

  2. Survival Outcomes by Treatment Line (Kaplan-Meier)

    Time frame: From the date of initial anti-EGFR therapy administration, with a maximum follow-up assessment of up to 186 months

    Survival distributions are estimated using the Kaplan-Meier method to evaluate the variation in clinical outcomes (OS and PFS) stratified according to the treatment line in which anti-EGFR therapy was administered (first-line versus subsequent lines)

  3. OS and PFS Stratified by Age (Kaplan-Meier Method)

    Time frame: From the date of initial anti-EGFR therapy administration, with a maximum follow-up assessment of up to 186 months

    Association between the predictive value of Fusobacterium nucleatum and age at diagnosis (early-onset colorectal cancer, <50 years, versus late-onset colorectal cancer, ≥50 years).

  4. OS and PFS Stratified by Antibiotic Use (Kaplan-Meier Method)

    Time frame: "From the date of initial anti-EGFR therapy administration, with a maximum follow-up assessment of up to 186 months

    Impact of systemic antibiotic therapy administered during anti-EGFR treatment on OS and PFS, adjusted for baseline intratumoral Fusobacterium nucleatum burden.

  5. F. nucleatum Load by Tumor Mutational Profile, Assessed by ddPCR

    Time frame: Up to 186 months

    Independent predictive correlation between Fusobacterium nucleatum burden and the tumor mutational profile (BRAF, PIK3CA, TP53) as well as microsatellite instability (MSI)

Sponsors and collaborators

Lead sponsor

Barretos Cancer Hospital

Other

Registry information

Official study title

Association Between Intratumoral Fusobacterium Nucleatum Burden and Therapeutic Resistance to Anti-EGFR Monoclonal Antibodies in Metastatic Colorectal Cancer: An Integrated Analysis of Clinical and Molecular Data

Important dates

Study start
2024
Primary completion
2027
Study completion
2028
First posted
Jun 2, 2026
Registry last updated
Jun 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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