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

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.

Study Overview

• Status: Recruiting
• Conditions: Anatomic Stage IV Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8; Metastatic Breast Carcinoma
• Intervention / Treatment: Other: Diagnostic Laboratory Biomarker Analysis; Other: Cytology Specimen Collection Procedure; Other: Medical Chart Review

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.

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
      • Contact: Agnieszka K. Witkiewicz; Phone Number: 716-845-1224; Email: Agnieszka.Witkiewicz@roswellpark.org
      • Principal Investigator: Agnieszka K. Witkiewicz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.	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 Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Agnieszka K Witkiewicz, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2020
• Primary Completion (Anticipated): July 3, 2025
• Study Completion (Anticipated): July 3, 2025

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 20, 2020
• First Posted (Actual): August 26, 2020

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: I 571719 (Other Identifier: Roswell Park Cancer Institute); NCI-2020-05682 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No