FMT in Triple Negative Breast Cancer Guided by ctDNA

NCT07292142 | Not Yet Recruiting Phase 1

• 1 other identifier: FRIDA
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 3

Brief Summary

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer, usually treated with chemotherapy and an immune checkpoint blockade (ICB) in the pre-operative or neoadjuvant phase. However, about 35% of tumors do not respond fully to this therapy, and patient prognosis is poor. Recent exciting data from our group and others suggest that the alteration of the gut microbiome via fecal microbiota transplantation (FMT) markedly affects the response to ICB in melanoma1-3. The investigators propose to test the safety and feasibility of altering the gut microbiome in the context of neoadjuvant therapy (NAT) for TNBC. This pilot study will assess the safety of FMT given with neoadjuvant chemo-immunotherapy and will determine the feasibility of conducting a future randomized clinical trial to test whether FMT improves the effectiveness of neoadjuvant chemotherapy and ICB in patients with TNBC. This study will be divided into two phases. In Phase I (observational phase), the investigators propose to test the feasibility of collecting stool and plasma samples in TNBC patients treated with neoadjuvant therapy (NAT) without FMT treatment. In Phase II (interventional phase), patients will undergo the sample collection procedures as in Phase I, but in addition, the investigators will assess the safety and feasibility of FMT treatment in combination with NAT.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• To evaluate the safety of combining Fecal Microbial Transplantation (FMT) using intestinal bacteria existing in the stool of healthy donors with immunotherapy/chemotherapy in triple-negative breast cancer patients.

  Toxicity assessments and concurrent medication review will occur at every visit throughout chemotherapy/immunotherapy treatment. Any adverse events after FMT administration will be followed until resolution or until judged stable by the investigator.

  20 months

• Feasibility of giving FMT is triple negative breast cancer patients treated with chemotherapy / immunotherapy prior surgery.

  The feasibility of FMT in both cohorts will be determined based on the proportion of patients that completed each step of the study. The investigators will assess the proportion approached and declined, approached and consented, consented and withdrew before FMT, consented, screened and successfully took the FMT, and able and willing to provide post-FMT stool samples.

  7 months

Study Arms (3)

Phase I

EXPERIMENTAL

In preparation for Phase II of the protocol, Phase I of the study will evaluate the feasibility of stool and plasma sample collection at different time points in TNBC patients receiving standard of care NAT.

Other: No Intervention.

Phase II - Cohort 1

EXPERIMENTAL

Phase II aims to assess the safety and feasibility of adding FMT to the treatment regimen of patients with TNBC receiving standard of care neoadjuvant chemotherapy plus immunotherapy. As this FMT regimen has never been combined with chemo-immunotherapy in TNBC, the goal is to assess safety and feasibility first. Exploratory analyses of markers of tumor response (ctDNA and pCR rate) and gut microbiome will also be conducted before embarking on a larger study. Phase II will comprise two cohorts. Cohort 1 will be administering FMT before starting standard systemic anti-cancer therapy, in this case, NAT for early TNBC.

Drug: Fecal Microbiota Transplantation (FMT)

Phase II - Cohort 2

EXPERIMENTAL

Phase II aims to assess the safety and feasibility of adding FMT to the treatment regimen of patients with TNBC receiving standard of care neoadjuvant chemotherapy plus immunotherapy. As this FMT regimen has never been combined with chemo-immunotherapy in TNBC, the goal is to assess safety and feasibility first. Exploratory analyses of markers of tumor response (ctDNA and pCR rate) and gut microbiome will also be conducted before embarking on a larger study. Phase II will comprise two cohorts. In Cohort 2, patients with ctDNA+ persistence from baseline to post-cycle 1 NAT (high-risk of non-pCR) will receive "rescue" FMT therapy at mid-treatment of NAT.

Drug: Fecal Microbiota Transplantation (FMT)

Interventions

No Intervention. OTHER

No FMT will be given in Phase I

Phase I

Fecal Microbiota Transplantation (FMT) DRUG

The investigators propose to test the safety and feasibility of altering the gut microbiome in the context of neoadjuvant therapy (NAT) for TNBC. This pilot study will assess the safety of FMT given with neoadjuvant chemo-immunotherapy and will determine the feasibility of conducting a future randomized clinical trial to test whether FMT improves the effectiveness of neoadjuvant chemotherapy and ICB in patients with TNBC.

Phase II - Cohort 1; Phase II - Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PHASE 1
• Patients must be 18 years old or older.
• Patients must have a confirmed diagnosis of TNBC (defined as estrogen receptor expression 0-10%, progesterone receptor expression 0-10%, and HER-2/neu negative (immunohistochemistry 0, 1+, or 2+ and fluorescent in-situ hybridization negative for HER-2 gene amplification) and are about to start neoadjuvant chemotherapy.
• Patients with ECOG performance of 0-2.
• Patients who are willing to provide serial stool and blood samples.
• Patients must be able to provide written informed consent
• Patients with available primary tumor biopsy tissue for molecular analysis
• PHASE 2
• Patients must be 18 years old or older.
• Patients must have a confirmed diagnosis of TNBC (defined as estrogen receptor expression 0-10%, progesterone receptor expression 0-10%, and HER-2/neu negative (immunohistochemistry 0, 1+, or 2+ and fluorescent in-situ hybridization negative for HER-2 gene amplification) and are about to start neoadjuvant chemotherapy-immunotherapy.
• Patients with ECOG performance of 0-2.
• Patients must be able to provide written informed consent and understand the infectious risks associated with FMT administration.
• Ability to ingest capsules.
• Patients receiving systemic steroids at physiologic doses are permitted to enroll assuming steroid dose is not above the acceptable threshold (\>10 mg prednisone daily or equivalent).

You may not qualify if:

• PHASE 1
• Clinical or radiological evidence of metastatic disease.
• Known infection with HIV or hepatitis.
• Pregnant woman.
• PHASE 2
• Previous anti-PD-1 treatment.
• Patient with a secondary malignancy.
• Pregnant or breastfeeding or expecting to conceive children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Current exposure to high-dose oral or intravenous corticosteroids (\>10 mg of prednisone daily or equivalent). Patients who require intermittent use of bronchodilators or local steroid injections are not excluded from the study.
• Absolute neutrophil count \<1.0 within 48 hours of planned FMT administration
• Has a diagnosis of immunodeficiency (for example, HIV or transplantation) or any other form of immunosuppressive therapy before trial treatment.
• Ongoing use of antibiotics or previous use of antibiotics one week before the FMT procedure.
• Probiotic supplements and food products labeled as containing probiotics must be discontinued a minimum of 24 hours before FMT administration and are not permitted during the course of neoadjuvant immunotherapy treatment.
• Presence of a chronic intestinal disease (for example, celiac, malabsorption, and colonic tumor).
• Presence of absolute contraindications to FMT administration, including toxic megacolon, severe dietary allergies (for example, shellfish, nuts, or seafood), and inflammatory bowel disease.

Sponsors & Collaborators

• Jewish General Hospital: lead

Study Sites (3)

London Health Sciences Center

London, Ontario, Canada

Location

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The first participants recruited will be part of the Phase 1 or the trial until the investigators reach the target number of participants. The investigators will them open the recruitment of the Phase 2 Cohort 1, until the target number of participants is reached, and that the Phase 2 Cohort 2 will be open for recruitment.

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 18, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2031
• Last Updated: December 18, 2025

Record last verified: 2025-06

Locations

CA (3)