Exploring the gut microbiome in breast cancer patients treated with CDK4/6 inhibitors

A Study of the Association of the Gut and Tumor Microbiome With Disease and Treatment Outcome of CDK4/6 Inhibitors in Hormone Receptor-positive HER2-negative Breast Cancer

This study is trying to see how the bacteria in the gut affects treatment results for women with a specific type of breast cancer who are taking a new medication.

Quick facts

• Study type: Observational
• Enrollment: 100 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain (other)
• Drugs / interventions: prednisone
• Locations: 3 sites (Brussels and 2 other locations)
• Trial ID: NCT06171360 on ClinicalTrials.gov

What this trial studies

This observational study investigates the relationship between the gut microbiome and treatment outcomes in patients with hormone receptor-positive, HER2-negative breast cancer receiving CDK4/6 inhibitors. It aims to analyze the composition and changes in the gut microbiome, along with immune, metabolic, and cytokine biomarkers, before and during treatment. By utilizing non-invasive stool and blood samples, the study seeks to identify potential biomarkers that could predict responses to CDK4/6 inhibition, ultimately paving the way for new treatment combinations for patients with poor prognosis.

Who should consider this trial

Good fit: Ideal candidates include adults with untreated hormone receptor-positive, HER2-negative advanced breast cancer who are starting first-line treatment with a CDK4/6 inhibitor.

Not a fit: Patients with HER2-positive breast cancer or those who have received prior systemic therapy within the last six months may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to the identification of biomarkers that enhance treatment personalization for breast cancer patients.

How similar studies have performed: While studies have explored the impact of the gut microbiome on cancer treatment, this specific approach focusing on CDK4/6 inhibitors is relatively novel.

Eligibility criteria

\* Cohort of metastatic HR-positive HER2-negative breast cancer :

Inclusion Criteria:

Patients that respond to each of these criteria can be included :

* Diagnosis of previously untreated HR+ HER2- advanced breast cancer (defined as locally advanced and unresectable, or metastatic). HR+ defined as positive estrogen receptors as per local laboratory testing. HER2- defined as negative ISH test or an IHC status of 0 or 1+ as per local laboratory testing.
* Planned first-line treatment with an endocrine therapy (aromatase inhibitor or fulvestrant) and a CDK4/6i.
* Male or female ≥ 18 years of age at the time the informed consent is signed.
* Being able to provide written informed consent.
* Patients with a history of early breast cancer are allowed providing systemic therapy (including adjuvant endocrine therapy) was discontinued more than 6 months ago.
* Patients are willing and able to comply with the protocol for the duration of the study including sample collection.
* Paraffin-embedded tumor tissue available at diagnosis of metastatic disease (inclusion to be discussed if not available).

Exclusion Criteria:

Patients who respond to any of these criteria are excluded :

* Administration of the CDK4/6i already started.
* Concurrent or previous non breast-related malignancy in the last 3 years prior to the start of the study treatment (with the exception of a history of adequately treated cervical carcinoma in situ or non-melanoma skin cancer).
* Treatment or chronic prevention of an infection through oral or intravenous antibiotic administered less than 1 month ago. History of unique antibiotic administration as prophylaxis for an invasive procedure is allowed.
* Active disease requiring treatment with an immunomodulatory agent. Low dose oral corticosteroids (equivalent to 8 mg or less of prednisone) or topical corticosteroids are allowed.
* Serological positivity for human immunodeficiency virus (HIV) or hepatitis C (HCV).
* Known active hepatitis.
* Active inflammatory bowel disease or documented malabsorption.
* Alcohol consumption (\>3 glasses/day).

  * Cohort of early HR-positive HER2-negative breast cancer at high risk of relapse :

Inclusion criteria :

Patients that respond to each of these criteria can be included :

* Early HR+ HER2- node-positive breast cancer considered at high risk of relapse (≥ 4 positive lymph nodes, or 1-3 positive lymph nodes and either or both grade 3 or tumor size \> 5 cm). HR+ defined as positive estrogen receptors as per local laboratory testing. HER2- defined as negative ISH test or an IHC status of 0 or 1+ as per local laboratory testing.
* Planned adjuvant treatment with a CDK4/6i, in combination with an endocrine therapy (aromatase inhibitor or tamoxifen, with or without LHRH agonists).
* Male or female ≥ 18 years of age at the time the informed consent is signed.
* Being able to provide written informed consent.
* Patients are willing and able to comply with the protocol for the duration of the study including sample collection.
* Paraffin-embedded tumor tissue available at diagnosis of the disease or at surgical resection (inclusion to be discussed if not available).

Exclusion criteria :

Patients who respond to any of these criteria are excluded :

* Administration of the CDK4/6i already started. Ongoing administration of the endocrine therapy before study inclusion is allowed.
* Concurrent or previous non breast-related malignancy in the last 3 years prior to the start of the study treatment (with the exception of a history of adequately treated cervical carcinoma in situ or non-melanoma skin cancer).
* Treatment or chronic prevention of an infection through oral or intravenous antibiotic administered less than 1 month ago. History of unique antibiotic administration as prophylaxis for an invasive procedure is allowed.
* Active disease requiring treatment with an immunomodulatory agent. Low dose oral corticosteroids (equivalent to 8 mg or less of prednisone) or topical corticosteroids are allowed.
* Serological positivity for human immunodeficiency virus (HIV) or hepatitis C (HCV).
* Known active hepatitis.
* Active inflammatory bowel disease or documented malabsorption.
* Alcohol consumption (\>3 glasses/day).

Where this trial is running

Brussels and 2 other locations

• Institut Jules Bordet — Brussels, Belgium (RECRUITING)
• Cliniques universitaires Saint-Luc — Brussels, Belgium (RECRUITING)
• CHU UCL Namur — Namur, Belgium (RECRUITING)

Study contacts

• Principal investigator: Cédric Van Marcke, MD, PhD — Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Study coordinator: Cédric Van Marcke, MD, PhD

Conditions: Breast Cancer