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: 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 CT or PET/CT scans that are part of standard of care treatment, and from DEXA scans (as part of proposed study). The investigators will also conduct body measurements with measuring tape, and will draw blood tests to assess for fat biomarkers.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Estefania Hernandez; Phone Number: 718-405-8126; Email: eshernande@montefiore.org
• Study Contact Backup: Name: Jesus Anampa, MD; Phone Number: 718-405-8505; Email: janampa@montefiore.org

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center
      • Contact: Estefania Hernandez; Phone Number: 718-405-8126; Email: eshernande@montefiore.org
      • Principal Investigator: Jesus Anampa, MD
      • Contact: Jesus D Anampa, MD,MS; Phone Number: 718-405-8505; Email: janampa@montefiore.org
      • Sub-Investigator: Joseph Sparano, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• 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 ER and/or PR positive, Her2 negative based on current 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.
• 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.
• Recent radiation or chemotherapy within 4 weeks
• 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 stereotatactic 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

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.We hypothesize 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 their standard of care, and body fat mass will be obtained from DEXA scan(as part of proposed study)

Diagnostic test: CT scans; Patients will undergo CT or PETCT as part of their standard of care; Diagnostic test: DEXA scan; Patients will undergo DEXA scan to measure body fat mass. This is part of proposed study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body fat mass (BFM)	body fat mass will be obtained from dual-energy x-ray absorptiometry (DEXA).	24 months
Skeletal muscle index (SMI)	Skeletal muscle index (SMI) is defined as muscle area at L3 cross section from CT scans in cm2 divided by height in meters squared	24 months
Body lean mass (BLM)	body lean mass(BLM) will be obtained from dual-energy x-ray absorptiometry (DEXA).	24 months
Glucose	serum glucose will be measured	24 months
Waist-to-hip ratio	waist-to-hip ratio will be measured with measuring tape.	24 months

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): December 1, 2025
• Study Completion (Estimated): December 1, 2025

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): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

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: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• 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