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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2020-05682 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| I 571719 | Other Identifier | Roswell Park Cancer Institute |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cytology Specimen Collection Procedure | Other | Undergo collection of blood, tissue, ascites or pleural effusions, and fresh body fluids or fresh biopsy samples |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| Examination of biomarkers of response | Will examine biomarkers of response/resistance and association with long term outcomes relative to pretreatment controls. | Up to 5 years |
| Single-nucleotide polymorphisms |
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
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:
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Patients with estrogen receptor positive (ER+)/HER2 negative (-) metastatic breast cancer, who are being or have been treated with ciclib-based therapies
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| Name | Affiliation | Role |
|---|---|---|
| Agnieszka K Witkiewicz | Roswell Park Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Roswell Park Cancer Institute | Recruiting | Buffalo | New York | 14263 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41576303 | Derived | 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. | |
| 40506447 |
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Blood, tissue, ascites or pleural effusions, fresh body fluids or fresh biopsy,
|
| Diagnostic Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Medical Chart Review | Other | Patient's electronic health records are reviewed |
|
|
| 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 |
Blood will be collected to interrogate single-nucleotide polymorphisms in CYP3A4 and related genes associated with metabolism of ciclib compounds. These polymorphisms will be related to dose limiting toxicities and dose interruptions. Blood samples for pharmacokinetic and pharmacogenomic analysis will be drawn during regular laboratory blood draws.
| Day 8 to day 18 of cycle 1 |
| Circulating cell free DNA (cfDNA) | Serial peripheral blood samples will be prospectively collected at specified time points and processed for cfDNA and circulating tumor cells (CTC) isolation. CTCs will be utilized for the development of 3-dimensional (3D) organoid cultures and CTC-derived xenograft models. | Up to 5 years |
| Development of functional models (patient-derived models) from individuals with progressive disease | Will only employ tissues and /or body fluids that are being discarded or do not involve any additional procedures for the patients. This includes, excess tissue that is not required for diagnosis or pleural effusions or peritoneal ascites. Cells isolated from the samples will be used for the development of organoid or PDX models. | Up to 5 years |
| 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. |
| 37704753 | 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. |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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