CDK and Body Composition Study

Pilot Study Assessing the Effect of Cyclin-dependent Kinase 4/6 Inhibitors on Body Composition in Patients With ER+/HER2- Metastatic Breast Cancer

The goal of this study is to evaluate changes in body composition among patients who are treated with cyclin-dependent kinase (CDK) 4/6 inhibitors (abemaciclib, ribociclib, or palbociclib).

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Diagnostic test: CT scans; Diagnostic test: DEXA scan

Detailed Description

The goal of this study is to evaluate changes in body composition among patients who are treated with cyclin-dependent kinase (CDK) 4/6 inhibitors (abemaciclib, ribociclib, or palbociclib). There is preliminary data suggesting that these drugs have more effect on body fat mass than body muscle mass. These drugs have already been approved by U.S Food and Drug Administration (FDA) to treat ER+/HER2- metastatic breast cancer. The investigators will follow up body composition changes among patients who receive CDK 4/6 inhibitors as part of their standard of care. Body composition changes will be measured from Computed Tomography (CT) or Positron Emission Tomography/Computed Tomography (PET/CT) scans that are part of standard of care treatment, and from DEXA scans (DEXA is optional and will be performed only if available). The investigators will also conduct body measurements with measuring tape and will draw blood tests to assess for fat biomarkers.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• United States
  • New York
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center

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 who are being asked to participate in this study because they have metastatic ER+/HER2- breast cancer, and their doctor is offering treatment with CDK 4/6 inhibitors as standard of care treatment.

Description

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the breast that is Estrogen Receptor (ER) and/or Progesterone Receptor (PR) positive based on current American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines
• Metastatic or locally advanced/inflammatory, unresectable breast cancer not amenable to potentially curative surgery
• Measurable and/or non-measurable as defined by RECIST 1.1 criteria
• Patients must be a candidate to start an FDA approved CDK 4/6 inhibitor (palbociclib, ribociclib, abemaciclib) as part of standard of care treatment
• Female, or male patients, and age >=18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Ability to understand and the willingness to sign a written informed consent document
• Concomitant therapy with bisphosphonates, RANKL inhibitors or growth-colony-stimulating factor (G-CSF) is allowed as per physician decision

Exclusion Criteria:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to CDK 4/6 inhibitors or other agents used in the study (e.g., fulvestrant, letrozole, anastrozole, exemestane)
• BMI < 18.5
• Prior CDK 4/6 use in any setting
• Inability to undergo anthropometric measurements
• Inability to undergo CT scan imaging
• Women of child-bearing potential must not be pregnant or breast feeding. They must also agree to use adequate contraception (hormonal or barrier method of birth control) and not be breast feeding prior to study entry, for the duration of study participation, and for up to 10 days after completion of all protocol therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study or up to 10 days after completion of protocol therapy, she should inform her treating physician immediately
• Intercurrent illness that would substantially increase the risk of treatment associated complications (e.g., active infection, uncontrolled diabetes mellitus or hypertension)
• Psychiatric illness/social situations that would interfere with the patient's ability to comply with the treatment regimen
• Patients with untreated brain metastasis are excluded. Patients with a prior history of brain metastasis are eligible if they have received prior brain radiation (whole brain or stereotactic radiosurgery) or surgery, have stable intracranial disease for at least 3 months after completion of local therapy, and are not taking corticosteroids for treatment of brain metastasis
• Patients who have not recovered (i.e., CTCAE Grade ≤1 or baseline) from an adverse event due to a previously administered agent, excluding alopecia
• Patients with inability to swallow and retain pills
• Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption
• Patients with active implanted medical devices (cardiac pacemakers, defibrillators or patients connected to electronic life support devices)

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

ER+/HER2- metastatic breast cancer; Subjects have metastatic ER+/HER2- breast cancer, and their doctor is offering treatment with CDK 4/6 inhibitors as standard of care treatment. It is hypothesized that cyclin-dependent kinase (CDK) 4/6 inhibitors decrease fat mass among women with ER+/HER2- metastatic breast cancer without significant effect in the skeletal mass. Body composition will be obtained from CT scans (CT or PETCT) as part of standard of care, and body fat mass will be obtained from DEXA scan (DEXA will be performed only if available)

Diagnostic test: CT scans; Patients will undergo CT or PETCT as part of standard of care; Diagnostic test: DEXA scan; Patients will undergo DEXA scan to measure body fat mass (DEXA will be performed only if available)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total adipose tissue (TAT)	Total Adipose tissue (TAT) is defined as the sum of intramuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) obtained from L3 cross section from CT scans. Only patients who complete 24 weeks of CDK 4/6 inhibitor treatment and have no radiological/clinical signs of disease progression will be included in the analysis of primary endpoint. Results will be calculated and summarized in area (cm²).	From Baseline and 6 months after CDK 4/6 inhibitor therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Fat Mass (BFM) using Dual-energy X-ray Absorptiometry (DEXA)	Body Fat Mass will be obtained from dual-energy x-ray absorptiometry (DEXA). The DEXA scan calculates the ratio of soft tissue attenuation at different X-ray energies. Results are measured and reported in kilograms (kg). DEXA scans are optional and will be performed only if available.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Body Lean Mass (BLM) using Dual-energy X-ray Absorptiometry (DEXA)	Body Lean Mass (BLM) will be obtained from dual-energy x-ray absorptiometry (DEXA). The DEXA scan calculates the ratio of soft tissue attenuation at different X-ray energies. Results are measured and reported in kilograms (kg). DEXA scans are optional and will be performed only if available.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Skeletal muscle index (SMI)	Skeletal muscle index (SMI) will be obtained by dual-energy x-ray absorptiometry (DEXA). The DEXA scan will be used to measure the amount of lean muscle in the body. SMI is defined as muscle area at L3 cross section from CT scans in cm^2 divided by height in meters squared. DEXA scans are optional and will be performed only if available.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Adipose Serum Biomarkers - Fasting Glucose	Fasting glucose levels in blood sera will be measured using a glucose blood sugar test. Normal ranges vary based on the health of the individual however standard glucose concentrations are between 70 mg/dL (3.9 mmol/L) -100 mg/dL (5.6 mmol/L). Glucose levels between 100-125 mg/dL (5.6-6.9 mmol/L) may be indicative of prediabetes. Fasting glucose levels >126 mg/dL on successive tests is correlated with diabetes. Results will be summarized and reported.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Adipose Serum Biomarkers - Lipid Panel (Total Cholesterol and LDL cholesterol, HDL cholesterol, and Triglycerides)	A lipid panel will be used to assess Total cholesterol, LDL Cholesterol, HDL Cholesterol, and triglyceride levels in blood sera samples. Each parameter has unique ranges and can vary by age, weight, and sex; however, High concentrations of Total cholesterol and LDL cholesterol increases the risk of coronary heart disease and atherosclerosis. HDL cholesterol ("good cholesterol") removes excess cholesterol from the body. High triglyceride levels also increase the risk of cardiovascular disease. Results for each parameter will be summarized and reported in mg/dL.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Adipose Serum Biomarkers - Dehydroepiandrosterone Sulphate (DHEAS)	DHEAS levels in blood sera will be measured using a DHEA-sulfate (DHEAS) blood test. This test can be used to check the function of the adrenal glands. Normal ranges vary based on age, gender and laboratory; however, high concentrations could be indicative of adrenal tumors, Cushing's disease, polycystic ovary syndrome (PCOS), or adrenal hyperplasia. Results will be summarized and reported in ug/dL.	Baseline and 6 months after CDK 4/6 therapy
Adipose Serum Biomarkers - Insulin	Insulin levels in blood sera will be measured using an insulin blood test. Insulin is a hormone that regulates glucose absorption. Normal ranges vary based on the type of test administered and the health of the individual; however, standard fasting insulin concentrations are usually <25 mIU/L. Higher concentrations can be indicative of insulin resistance. Results will be summarized and reported.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Adipose Serum Biomarkers - Leptin	Leptin will be assessed using a leptin blood test that measures the concentration of leptin in blood sera. Leptin is a hormone that helps regulate appetite and energy levels. Standard ranges vary based on age, gender, body mass index, and other variables; however, ranges are generally between 0.5-15.2 ng/mL for females and 0.5-12.5 ng/mL for males. Results will be summarized and reported.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Adipose Serum Biomarkers - Free Leptin Index (FLI)	FLI will be assessed by blood test and calculated as the ratio of total leptin and soluble leptin receptor (sOB-R) concentrations. FLI is a biomarker of leptin resistance and the status of leptin action. High FLI is a risk factor for obesity and is associated with several chronic diseases. Results will be summarized and reported.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Adipose Serum Biomarkers - Adiponectin	Adiponectin will be assessed using an adiponectin test that measures the concentration of adiponectin in the blood. Adiponectin is a protein hormone produced by fat cells that helps regulate blood sugar and fat metabolism. Lower levels of adiponectin in blood sera are often linked to conditions like obesity, type 2 diabetes, and heart disease. A normal adiponectin blood test result is generally 5-30 ug/mL but can vary depending on age and body mass index (BMI). Results will be summarized and reported.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Adipose Serum Biomarkers - High-sensitivity C-reactive protein (hsCRP)	hsCRP will be measured and reported by blood test. hsCRP measures the concentration of C-reactive protein (CRP) in blood. CRP is a protein that increases in response to inflammation and is correlated with adverse cardiovascular and cerebrovascular outcomes. Normal results are generally risk stratified with concentrations <1.0 mg/dL indicating a low risk of cardiovascular disease; concentrations between 1.0-3.0 mg/dL indicating an average risk of cardiovascular disease; and concentrations >3.0 mg/dL indicating a high risk of cardiovascular disease. Results will be summarized and reported.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Body Fat Mass (BFM) using Bioimpedance spectroscopy (BIS)	BFM will be measured with the use of bioimpedance spectroscopy (BIS). BIS is a non-invasive method that takes measurements at 256 different frequencies and uses mathematical modeling to calculate electrical resistance throughout the body. Fat tissue has significantly higher resistance compared to lean muscle tissue. The total weight of body fat estimated by the BIS analysis will be expressed in kilograms and summarized for the group.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Body Fat-Free Mass (FFM)	FFM will be derived based on the BFM readout obtained from the BIS analysis. The "fat-free mass" will be calculated by subtracting the total body weight minus the estimated BFM obtained by BIS analysis, based on electrical resistance through the body. This result will be expressed in kilograms and summarized for the group.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Anthropometric measurements - Body Mass Index (BMI)	BMI will be determined by obtaining height and body weight measurements. It is calculated by dividing body weight in kilograms (kg) by height in meters squared (m^2). A BMI of 30 kg/m^2 or higher has been used to define obesity in most reports, including those showing an association between obesity and increased risk of cancers, cancer mortality, and mortality from all causes. Group results will be summarized and reported.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Anthropometric measurements - Skin fold thickness (biceps, triceps, subscapular, and suprailiac)	Skin fold thickness will be measured with the use of calipers. Skin fold thickness measurements will be obtained for the biceps, triceps, subscapular, and suprailiac sites. Calipers will be used to pinch the skin and lift it away from the muscle at each site and measure the thickness of skin folds at each location. Values will be summarized in millimeters (mm) for the group and reported. Skin fold thickness measurements provide an overall picture of subcutaneous fat distribution.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Anthropometric measurements - Abdominal circumference	Abdominal circumference is a measurement of the horizontal distance around the abdomen. Abdominal circumference will be assessed by determining the midpoint between the lower rib margin and the iliac crest and measuring the circumference at the midpoint, in centimeters, with measuring tape while breathing normally. Group results will be summarized. An enlarged abdominal circumference can be a sign of obesity and a risk factor for disease.	Baseline and 6 months after CDK 4/6 inhibitor therapy
Anthropometric measurements - Waist-to-hip ratio	Waist-to-hip ratio will be measured with measuring tape by measuring the narrowest part of the waist followed by the widest part of the hips and dividing the waist measurement by the hip measurement. While normal values can vary, a healthy waist-to-hip ratio is generally considered to be below 0.9 for men and 0.85 for women, according to the World Health Organization (WHO). Group results will be summarized.	Baseline and 6 months after CDK 4/6 inhibitor therapy

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Jesus Anampa, MD, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2019
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: October 3, 2018
• First Posted (Actual): October 5, 2018

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Body composition; body fat mass; cyclin-dependent kinase (CDK) 4/6 inhibitors; metastatic ER+/HER2- breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Investigative Techniques; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Chemistry Techniques, Analytical; Radiography; Densitometry; Photometry; Image Interpretation, Computer-Assisted; Radiographic Image Enhancement; Image Enhancement; Photography; Tomography, X-Ray; Absorptiometry, Photon; Tomography, X-Ray Computed
• Other Study ID Numbers: 2018-9567

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No