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

NCT04526587 | Recruiting

• 2 other identifiers: I 571719NCI-2020-05682
• Study Type: observational
• Target: 700
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Breast Carcinoma; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (11)

• Collection of clinical characteristics

  Will be summarized by ciclib treatment regimen using the appropriate descriptive statistics. Differences will be evaluated using the Kruskal-Wallis and Chi-square tests, as appropriate.

  Up to 5 years

• Overall survival on ciclib

  Will be summarized by treatment regimen using standard Kaplan-Meier methods, with comparisons made using the log rank test. Cox regression models with time-dependent variables may be considered to account for changing treatment regimens and other patient characteristics.

  Up to 15 years

• Progression-free survival on ciclib

  Will be summarized by treatment regimen using standard Kaplan-Meier methods, with comparisons made using the log rank test. Cox regression models may be considered to adjust for prior therapies and other patient characteristics.

  Up to 15 years

• Progression-free survival on subsequent therapies

  Will be summarized by treatment regimen using standard Kaplan-Meier methods, with comparisons made using the logrank test. Cox regression models may be considered to adjust for prior therapies and other patient characteristics.

  Up to 15 years

• Site of the metastatic disease and time to progression

  Development of and location of metastatic disease will be summarized using the appropriate descriptive statistics.

  Up to 5 years

• Incidence of treatment related toxicities

  Will be summarized by ciclib treatment regimen using frequencies and relative frequencies. Comparisons may be made using Fisher's exact test. Associations between toxicity rates and patient demographic/clinical characteristics may be evaluated using logistic regression models.

  Up to 5 years

• Genetic variance of genes associated with ciclib metabolism

  Will be summarized in the overall sample and by treatment regimen using the appropriate descriptive statistics and graphical summaries. The association between these genetic features and toxicity and survival outcomes will be evaluated using stratified Cox regression models, where genotype will be the stratification factor. Additional models may be considered to account for other demographic or clinical characteristics. Hazard ratios with 95% confidence intervals will be obtained from model estimates.

  Up to 5 years

• Quantitative biomarker expressions

  Will be summarized in the overall sample and by treatment regimen using the appropriate descriptive statistics and graphical summaries. The association between baseline biomarkers and survival outcomes will be evaluated using stratified Cox regression models, where treatment regimen will be the stratification factor. Additional models may be considered to account for other demographic or clinical characteristics. Hazard ratios with 95% confidence intervals will be obtained from model estimates.

  Up to 5 years

• Development of patient-derived models from resistant disease

  Will be evaluated to functionally assess the mechanisms occurring with resistance. No formal statistical analyses will be performed in regards to the development of organoid and patient-derived xenograft (PDX) models.

  Up to 5 years

• Socio-economic features related to the use of ciclibs

  Will be elucidated clinically in the Roswell Park catchment area. Treatment regimens and sequences may be summarized by patient demographic and socio-economic characteristics using frequencies and relative frequencies. Associations may be evaluated using Chi-square tests.

  Up to 5 years

• Clinical course of CDK4/6 inhibitor treated patients in the "real-world" setting

  Will involve interrogating ciclib treatment patterns, treatment choices post progression, toxicities, clinical responses following progression, and ultimately differences in overall survival.

  Up to 5 years

Other Outcomes (4)

• Examination of biomarkers of response

  Up to 5 years

• Single-nucleotide polymorphisms

  Day 8 to day 18 of cycle 1

• Circulating cell free DNA (cfDNA)

  Up to 5 years

Study Arms (1)

Basic science (medical chart review, biospecimen collection)

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.

Other: Cytology Specimen Collection Procedure; Other: Diagnostic Laboratory Biomarker Analysis; Other: Medical Chart Review

Interventions

Cytology Specimen Collection Procedure OTHER

Undergo collection of blood, tissue, ascites or pleural effusions, and fresh body fluids or fresh biopsy samples

Also known as: Cytologic Sampling

Basic science (medical chart review, biospecimen collection)

Diagnostic Laboratory Biomarker Analysis OTHER

Correlative studies

Basic science (medical chart review, biospecimen collection)

Medical Chart Review OTHER

Patient's electronic health records are reviewed

Also known as: Chart Review

Basic science (medical chart review, biospecimen collection)

Eligibility Criteria

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

Study Population

Patients with estrogen receptor positive (ER+)/HER2 negative (-) metastatic breast cancer, who are being or have been treated with ciclib-based therapies

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

Related Publications (3)

• 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 DERIVED

• 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 DERIVED

• 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 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood, tissue, ascites or pleural effusions, fresh body fluids or fresh biopsy,

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Agnieszka K Witkiewicz

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: August 26, 2020
• Study Start: July 3, 2020
• Primary Completion (Estimated): July 3, 2030
• Study Completion (Estimated): July 3, 2035
• Last Updated: November 13, 2025

Record last verified: 2025-11

Locations

US (1)