A Study of the Gut Microbiome in Hormone Receptor-positive HER2-negative Breast Cancer Treated With CDK4/6 Inhibitors

NCT06171360 | Recruiting

• 1 other identifier: 2022/31AOU/322
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

Ciclibiome is a prospective study including BC patients starting treatment with a CDK4/6 inhibitor (in the metastatic and in the adjuvant setting). This study will focus on the interplay between the gut microbiome (its composition and evolution during treatment), circulating immune, metabolic and cytokine biomarkers (before and during treatment), and response outcomes to the CDK4/6 inhibitor. The main aim of the study is to highlight the existence of a microbial, immune and/or metabolic biomarker of response to CDK4/6 inhibition in BC, assessable by a stool or blood sample examination. Ultimately, this will allow to study new potential combination partners for CDK4/6 inhibitors in escalation trials for poor prognosis patients.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (4)

• Pre-treatment gut microbiome composition

  The pre-treatment composition of the gut microbiome is defined by 16S rRNA sequencing of the stool samples collected at study inclusion.

  at study inclusion

• Pre-treatment gut metabolic profile

  The pre-treatment gut metabolic profile is defined by mass spectometry on the stool samples collected at study inclusion.

  at study inclusion

• Pre-treatment circulating immune population profile

  The pre-treatment circulating immune population profile is defined by FACS cytometry on the blood samples collected at study inclusion.

  at study inclusion

• Pre-treatment circulating metabolic profile

  The pre-treatment circulating metabolic profile is defined by mass spectometry on the plasma samples collected at study inclusion.

  at study inclusion

Secondary Outcomes (4)

• On-treatment gut microbiome composition

  at 3 months, 6 months, 1 year, 2 years, 5 years

• On-treatment gut metabolic profile

  at 3 months, 6 months, 1 year, 2 years, 5 years

• On-treatment circulating immune population profile

  at 3 months, 6 months, 1 year, 2 years, 5 years

• On-treatment circulating metabolic profile

  at 3 months, 6 months, 1 year, 2 years, 5 years

Study Arms (2)

Metastatic HR-positive HER2-negative breast cancer

Patients with metastatic HR+ HER2- BC starting a first line treatment with a CDK4/6 inhibitor (palbociclib, ribociclib, abemaciclib). Investigators will regularly collect blood and fecal samples for correlative translational research.

Early HR-positive HER2-negative breast cancer at high risk of relapse

Patients with early HR+ HER2- BC at high risk of relapse, starting adjuvant treatment with a CDK4/6 inhibitor (abemaciclib, ribociclib). Investigators will regularly collect blood and fecal samples for correlative translational research.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This prospective study will include HR-positive HER2-negative breast cancer patients starting treatment with a CDK4/6 inhibitor (both in the advanced and adjuvant setting).

You may qualify if:

• 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.

You may not qualify if:

• 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 :
• 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.

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead
• Jules Bordet Institute: collaborator

Study Sites (3)

Institut Jules Bordet

Brussels, 1070, Belgium

RECRUITING

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

RECRUITING

CHU UCL Namur

Namur, 5000, Belgium

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Fecal, blood and tumor samples

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Cédric Van Marcke, MD, PhD

  Cliniques universitaires Saint-Luc- Université Catholique de Louvain

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cédric Van Marcke, MD, PhD

CONTACT

+3227645106; cedric.vanmarcke@saintluc.uclouvain.be

Elodie Villar

CONTACT

+3227647938; elodie.villar@saintluc.uclouvain.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: December 14, 2023
• Study Start: November 15, 2022
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3)