Anatomic Stage IV Breast Cancer AJCC v8NCT04526587
Biomarkers and Clinical Features of Metastatic Breast Cancer in Patients Treated With CDK4/6 Inhibitors
An observational study of Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Breast Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8
- What is being tested?
- Cytology Specimen Collection Procedure, Diagnostic Laboratory Biomarker Analysis and Medical Chart Review
- How many people
- 700 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jul 2020to 3 Jul 2035
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with estrogen receptor positive (ER+)/HER2 negative (-) metastatic breast cancer, who are being or have been treated with ciclib-based therapies
Who may be able to join
- 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
Who cannot join
- Pregnant of nursing female subjects
- Unwilling or unable to follow protocol requirements
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Roswell Park Cancer Institute
Buffalo, New York, 14263
Agnieszka K. Witkiewicz, 716-845-1224, Agnieszka.Witkiewicz@roswellpark.org
Agnieszka K. Witkiewicz
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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.
- 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.
- Conditions
- Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8
- Being tested
- Cytology Specimen Collection Procedure, Diagnostic Laboratory Biomarker Analysis, Medical Chart Review
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytology Specimen Collection ProcedureOther
Also called Cytologic Sampling
Undergo collection of blood, tissue, ascites or pleural effusions, and fresh body fluids or fresh biopsy samples
Diagnostic Laboratory Biomarker AnalysisOther
Correlative studies
Medical Chart ReviewOther
Also called Chart Review
Patient's electronic health records are reviewed
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Cytology Specimen Collection Procedure; Other: Diagnostic Laboratory Biomarker Analysis; Other: Medical Chart Review |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2020
- Study start3 Jul 2020
- Primary completion3 Jul 2030 (estimated)
- Study completion3 Jul 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Anatomic Stage IV Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Agnieszka K Witkiewicz, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04526587
- Sponsor's protocol ID
- I 571719
- Other IDs
- NCI-2020-05682, I 571719
- Status last verified
- Nov 2025
- First submitted
- 18 Aug 2020
- Last updated
- 13 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 41576303Tzetzo 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.
PubMed 40506447Witkiewicz 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.
PubMed 37704753
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04526587
- Acronym / sponsor ID
- I 571719
- Conditions
- Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 700 participants (estimated)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Study start
- 3 Jul 2020 (actual)
- Primary completion
- 3 Jul 2030 (estimated)
- Study completion
- 3 Jul 2035 (estimated)
- First posted
- 26 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Basic science (medical chart review, biospecimen collection) | – | Other: Cytology Specimen Collection Procedure, Other: Diagnostic Laboratory Biomarker Analysis, Other: Medical Chart ReviewPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with estrogen receptor positive (ER+)/HER2 negative (-) metastatic breast cancer, who are being or have been treated with ciclib-based therapies
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- Pregnant of nursing female subjects
- Unwilling or unable to follow protocol requirements
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytology Specimen Collection ProcedureAlso: Cytologic SamplingUndergo collection of blood, tissue, ascites or pleural effusions, and fresh body fluids or fresh biopsy samples | Other | Basic science (medical chart review, biospecimen collection) |
| Diagnostic Laboratory Biomarker AnalysisCorrelative studies | Other | Basic science (medical chart review, biospecimen collection) |
| Medical Chart ReviewAlso: Chart ReviewPatient's electronic health records are reviewed | Other | Basic science (medical chart review, biospecimen collection) |
Primary outcome
Collection of clinical characteristics
Time frame: Up to 5 years
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.
Overall survival on ciclib
Time frame: Up to 15 years
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.
Progression-free survival on ciclib
Time frame: Up to 15 years
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.
Progression-free survival on subsequent therapies
Time frame: Up to 15 years
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.
Site of the metastatic disease and time to progression
Time frame: Up to 5 years
Development of and location of metastatic disease will be summarized using the appropriate descriptive statistics.
Incidence of treatment related toxicities
Time frame: Up to 5 years
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.
Genetic variance of genes associated with ciclib metabolism
Time frame: Up to 5 years
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.
Quantitative biomarker expressions
Time frame: Up to 5 years
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.
Development of patient-derived models from resistant disease
Time frame: Up to 5 years
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.
Socio-economic features related to the use of ciclibs
Time frame: Up to 5 years
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.
Clinical course of CDK4/6 inhibitor treated patients in the "real-world" setting
Time frame: Up to 5 years
Will involve interrogating ciclib treatment patterns, treatment choices post progression, toxicities, clinical responses following progression, and ultimately differences in overall survival.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2025.
- Derived from this study: PubMed 41576303O'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.
- Derived from this study: PubMed 40506447Tzetzo 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.
- Derived from this study: PubMed 37704753Witkiewicz 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Agnieszka K Witkiewicz principal investigator
Roswell Park Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anatomic Stage IV Breast Cancer AJCC v8 and Metastatic Breast Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Collection of clinical characteristics (time frame: Up to 5 years). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04526587, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2025.