Clinical trial NCT03697577: CDK and Body Composition Study
Official title: Pilot Study Assessing the Effect of Cyclin-dependent Kinase 4/6 Inhibitors on Body Composition in Patients With ER+/HER2- Metastatic Breast Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Cancer
Keywords: cyclin-dependent kinase (CDK) 4/6 inhibitors
Body composition
body fat mass
metastatic ER+/HER2- breast cancer
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
First posted: 2018-10-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
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.

Brief summary: 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).

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 (DEXA 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.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed adenocarcinoma of the breast that is ER and/or PR positive 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
* 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)

Primary outcomes:
measure: Total adipose tissue (TAT)
timeFrame: Baseline and 6 months after CDK 4/6 inhibitor therapy
Secondary outcomes:
measure: Body Fat Mass (BFM) using Dual-energy X-ray Absorptiometry (DEXA)
timeFrame: Baseline and 6 months after CDK 4/6 inhibitor therapy
measure: Body Lean Mass (BLM) using Dual-energy X-ray Absorptiometry (DEXA)
timeFrame: Baseline and 6 months after CDK 4/6 inhibitor therapy
measure: Skeletal muscle index (SMI)
timeFrame: Baseline and 6 months after CDK 4/6 inhibitor therapy
measure: Adipose Serum Biomarkers - Fasting Glucose
timeFrame: Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
measure: Adipose Serum Biomarkers - Lipid Panel (Total Cholesterol and LDL cholesterol, HDL cholesterol, and Triglycerides)
timeFrame: Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
measure: Adipose Serum Biomarkers - Dehydroepiandrosterone Sulphate (DHEAS)
timeFrame: Baseline and 3 months and 6 months after CDK 4/6 therapy
measure: Adipose Serum Biomarkers - Insulin
timeFrame: Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
measure: Adipose Serum Biomarkers - Leptin
timeFrame: Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
measure: Adipose Serum Biomarkers - Free Leptin Index (FLI)
timeFrame: Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
measure: Adipose Serum Biomarkers - Adiponectin
timeFrame: Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
measure: Adipose Serum Biomarkers - High-sensitivity C-reactive protein (hsCRP)
timeFrame: Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy
measure: Body Fat Mass (BFM) using Bioimpedance spectroscopy (BIS)
timeFrame: Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy, and every 3 months thereafter up to 24 months
measure: Body Fat-Free Mass (FFM)
timeFrame: Baseline and 3 months and 6 months after CDK 4/6 inhibitor therapy, and every 3 months thereafter up to 24 months
measure: Anthropometric measurements - Body Mass Index (BMI)
timeFrame: Baseline and every 4 weeks for the first 6 months after CDK 4/6 inhibitor therapy and every 3 months thereafter up to 24 months
measure: Anthropometric measurements - Skin fold thickness (biceps, triceps, subscapular, and suprailiac)
timeFrame: Baseline and every 4 weeks for the first 6 months after CDK 4/6 inhibitor therapy and every 3 months thereafter up to 24 months
measure: Anthropometric measurements - Abdominal circumference
timeFrame: Baseline and every 4 weeks for the first 6 months after CDK 4/6 inhibitor therapy and every 3 months thereafter up to 24 months
measure: Anthropometric measurements - Waist-to-hip ratio
timeFrame: Baseline and every 4 weeks for the first 6 months after CDK 4/6 inhibitor therapy and every 3 months thereafter up to 24 months
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Jesus Anampa, MD
role: PRINCIPAL_INVESTIGATOR
References: