Biomarkers and Clinical Features of Metastatic Breast Cancer in Patients Treated With CDK4/6 Inhibitors

Official title

The Roswell Park Ciclib Study: A Prospective Study of Biomarkers and Clinical Features of Advanced/Metastatic Breast Cancer Treated With CDK4/6 Inhibitors

Overview

This study investigates the clinical course of CDK4/6 inhibitor treated patients in the real-world setting among patients with breast cancer. CDK4/6 inhibitors may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Studying samples of blood, tissue, ascites or pleural effusions, and fresh body fluids or fresh biopsy, from patients with breast cancer that has spread to the other places in the body (metastatic) may help doctors learn more about cancer and the development of drug resistance in patients, and predict how well patients will respond to treatment.

Detailed description

PRIMARY OBJECTIVES:

I. Delineate clinical features of disease progression and responses to subsequent therapy following progression on ciclib-based therapy.

II. Define pharmacogenomics relationships that could provide a more precise approach to drug dosing.

III. Interrogate biomarkers related to response and acquired resistance in standard clinical practice.

IV. Develop patient-derived models from resistant disease to functionally assess the mechanisms occurring with resistance.

V. Elucidate the socio-demographic features related to the use of ciclibs clinically in the Roswell Park catchment area.

OUTLINE:

Patients electronic medical records are reviewed to capture clinical information, and patients undergo collection of blood, tissue, ascites or pleural effusions, and fresh body fluids or fresh biopsy samples for diagnosis/treatment decision, biomarker assessments, and description of mechanisms of resistance/response related to ciclib-therapy.

Interventions

• Other Cytology Specimen Collection Procedure
  Undergo collection of blood, tissue, ascites or pleural effusions, and fresh body fluids or fresh biopsy samples
• Other Diagnostic Laboratory Biomarker Analysis
  Correlative studies
• Other Medical Chart Review
  Patient's electronic health records are reviewed

Primary outcome measures

• Collection of clinical characteristics [Time frame: Up to 5 years]
• Overall survival on ciclib [Time frame: Up to 15 years]
• Progression-free survival on ciclib [Time frame: Up to 15 years]
• Progression-free survival on subsequent therapies [Time frame: Up to 15 years]
• Site of the metastatic disease and time to progression [Time frame: Up to 5 years]
• Incidence of treatment related toxicities [Time frame: Up to 5 years]
• Genetic variance of genes associated with ciclib metabolism [Time frame: Up to 5 years]
• Quantitative biomarker expressions [Time frame: Up to 5 years]
• Development of patient-derived models from resistant disease [Time frame: Up to 5 years]
• Socio-economic features related to the use of ciclibs [Time frame: Up to 5 years]

Eligibility criteria

Inclusion criteria

• All adult patients with ER+/HER2- metastatic breast cancer or HR+/HER2-node positive, high risk early breast cancer who are being or have been treated with ciclib-based therapies are eligible for inclusion in this study

• This includes patients receiving standard of care therapy for ER+/HER2- metastatic breast cancer, as well as those who would be eligible to participate in a non-interventional study while on a clinical study open at Roswell Park or St. Vincent's Hospital
• Screening will occur in breast oncology clinic, by review of patient medical records for the pending, ongoing, or past treatment with ciclib-based therapy
• Participant must understand the prospective nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form

Exclusion criteria

• Pregnant of nursing female subjects
• Unwilling or unable to follow protocol requirements

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 1 center

• Roswell Park Cancer Institute — Buffalo

Publications

• O'Connor TN, Schultz E, Kabraji S, Levine E, Williams AJ, Knudsen ES, Witkiewicz AK. Real-World Plasma Thymidine Kinase Activity in High-Risk and Metastatic Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Treated With Cyclin-Dependent Kinase 4/6 Inhibitors. JCO Precis Oncol. 2026 Jan;10:e2500346. doi: 10.1200/PO-25-00346. Epub 2026 Jan 23. PMID 41576303
• Tzetzo SL, Schultz E, Wang J, Rosenheck HR, Mahan S, Knudsen ES, Witkiewicz AK. Baseline cell cycle and immune profiles indicate CDK4/6 inhibitor response in metastatic HR + /HER2- breast cancer. NPJ Breast Cancer. 2025 Jun 12;11(1):54. doi: 10.1038/s41523-025-00767-2. PMID 40506447
• Witkiewicz AK, Schultz E, Wang J, Hamilton D, Levine E, O'Connor T, Knudsen ES. Determinants of response to CDK4/6 inhibitors in the real-world setting. NPJ Precis Oncol. 2023 Sep 13;7(1):90. doi: 10.1038/s41698-023-00438-0. PMID 37704753

Identifiers

NCT: NCT04526587 · I 571719 · NCI-2020-05682 · I 571719

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗