Metastatic Colorectal Cancer (CRC)NCT07619859
Impact of Fusobacterium Nucleatum on Response to Anti-EGFR Therapy in Metastatic Colorectal Cancer
An observational study of Metastatic Colorectal Cancer (CRC), run by Barretos Cancer Hospital at 1 site in Brazil.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer (CRC)
- How many people
- 500 participants
- Where
- 1 siteBrazil
- Study dates
- 5 Jul 2024to Jun 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population consists of patients diagnosed with metastatic (Stage IV) colorectal adenocarcinoma who received at least one cycle of anti-EGFR therapy (Cetuximab or Panitumumab) between January 2016 and December 2022 at the Hospital de Amor (Barretos, SP, Brazil). Eligible patients must have formalin-fixed paraffin-embedded (FFPE) tumor tissue samples available in the institutional biobank for molecular analysis. Patients with primary tumors outside the colon or rectum, non-adenocarcinoma histology, or with activating mutations in KRAS, NRAS, or BRAF (unless anti-EGFR was used in combination with BRAF inhibitors) are excluded.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official 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
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.
Read the detailed description
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.
- Conditions
- Metastatic Colorectal Cancer (CRC)
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 - High Fn | Patients with intratumoral Fusobacterium nucleatum burden above the median. | |
| Cohort 2 - Low/Negative Fn | Patients with intratumoral Fusobacterium nucleatum burden less than or equal to the median, or with undetectable infection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Proportion of patients who achieved complete or partial response as assessed according to standardized RECIST 1.1 criteria.
Measured: From the date of first anti-EGFR administration until disease progression, assessed up to 186 months
Overall Survival (OS)
Time elapsed from diagnosis to death from any cause
Measured: 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.
Progression-Free Survival (PFS).
Time elapsed from treatment initiation (for each line of therapy) to radiological disease progression or death.
Measured: 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
Secondary outcomes (5)
F. nucleatum Load by Tumor Topography and Paired Metastases, Assessed by ddPCR
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.
Measured: Up to 186 months.
Survival Outcomes by Treatment Line (Kaplan-Meier)
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)
Measured: From the date of initial anti-EGFR therapy administration, with a maximum follow-up assessment of up to 186 months
OS and PFS Stratified by Age (Kaplan-Meier Method)
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).
Measured: From the date of initial anti-EGFR therapy administration, with a maximum follow-up assessment of up to 186 months
OS and PFS Stratified by Antibiotic Use (Kaplan-Meier Method)
Impact of systemic antibiotic therapy administered during anti-EGFR treatment on OS and PFS, adjusted for baseline intratumoral Fusobacterium nucleatum burden.
Measured: "From the date of initial anti-EGFR therapy administration, with a maximum follow-up assessment of up to 186 months
F. nucleatum Load by Tumor Mutational Profile, Assessed by ddPCR
Independent predictive correlation between Fusobacterium nucleatum burden and the tumor mutational profile (BRAF, PIK3CA, TP53) as well as microsatellite instability (MSI)
Measured: Up to 186 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2026
- Study start5 Jul 2024
- Primary completion10 Dec 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal Cancer (CRC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Barretos Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Leticia Dias Costa, Barretos Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07619859
- Sponsor's protocol ID
- CAAE 72877217.8.0000.5437
- Status last verified
- May 2026
- First submitted
- 7 May 2026
- Last updated
- 4 Jun 2026
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT07619859
- Acronym / sponsor ID
- CAAE 72877217.8.0000.5437
- Conditions
- Metastatic Colorectal Cancer (CRC)
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Barretos Cancer HospitalUniversity, hospital or other
- Study start
- 5 Jul 2024 (actual)
- Primary completion
- 10 Dec 2027 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 2 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 - High Fn | – | –Patients with intratumoral Fusobacterium nucleatum burden above the median. |
| Cohort 2 - Low/Negative Fn | – | –Patients with intratumoral Fusobacterium nucleatum burden less than or equal to the median, or with undetectable infection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population consists of patients diagnosed with metastatic (Stage IV) colorectal adenocarcinoma who received at least one cycle of anti-EGFR therapy (Cetuximab or Panitumumab) between January 2016 and December 2022 at the Hospital de Amor (Barretos, SP, Brazil). Eligible patients must have formalin-fixed paraffin-embedded (FFPE) tumor tissue samples available in the institutional biobank for molecular analysis. Patients with primary tumors outside the colon or rectum, non-adenocarcinoma histology, or with activating mutations in KRAS, NRAS, or BRAF (unless anti-EGFR was used in combination with BRAF inhibitors) are excluded.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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
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.
5 secondary outcomes
F. nucleatum Load by Tumor Topography and Paired Metastases, Assessed by ddPCR
Time frame: Up to 186 months.
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
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
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
F. nucleatum Load by Tumor Mutational Profile, Assessed by ddPCR
Time frame: Up to 186 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
Related trials for Metastatic Colorectal Cancer (CRC)
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 1
A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)
Metastatic Colorectal Cancer
Not yet recruitingPhase 2
SAMe in Prevention of Oxaliplatin-associated Liver Injury
Colorectal Cancer, Liver Metastases
RecruitingPhase 1
A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors
Metastatic Solid Tumors
Not yet recruitingPhase 1/2
A Phase Ib/II Study of GFH276 in Combination With Chemotherapy (± Bevacizumab) or Cetuximab in Patients With RAS-mutant Metastatic Colorectal Cancer
CRC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Colorectal Cancer (CRC), run by Barretos Cancer Hospital at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: From the date of first anti-EGFR administration until disease progression, assessed up to 186 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.