Clinical trial NCT06572800: Tka Assay for CDK4/6i
Official title: Use of DiviTum-TKa as a Biomarker Assay for CDK4/6 Inhibitor Medication Compliance and Drug-Drug Interaction Assessment in ER/PR Positive Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anatomic Stage IV Breast Cancer AJCC v8
Metastatic HER2-Negative Breast Carcinoma
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2024-08-27
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: This clinical trial assesses whether using a test developed by DiviTum can identify optimal levels of CDK 4/6 inhibitor medications in the blood and whether assessing medical compliance and drug-drug interactions can optimize (improve) these levels in patients with estrogen receptor (ER) or progesterone receptor (PR) positive, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and are receiving CDK 4/6 inhibitors. CDK4/6 inhibitors in combination with endocrine therapy (ET) is first line treatment for metastatic hormone positive (ER/PR positive) breast cancer (mBC). Thymidine kinase is a biomarker (biological molecule found in blood, other body fluids, or tissues that is a sign of a condition or disease) that reflects cell proliferation (an increase in the number of cells as a result of cell growth and cell division). DiviTum-thymidine kinase activity (TKa) is a Food and Drug Administration approved assay which showed that a TKa is associated with the decreased likelihood of disease progression within 30 days or 60 days post testing. Using the DiviTum-TKa may improve medication compliance and remove potential drug-drug interactions in patients with ER/PR positive HER2-negative MBC.

Detailed description: PRIMARY OBJECTIVE:

I. To estimate the rate of improvement in CDK4/6 inhibitor response (i.e. moving from profile 3 to profiles 1 or 2) in cycles 2 and 3 after counseling for medication compliance and adjustment of potential deleterious drug-drug interactions.

SECONDARY OBJECTIVES:

I. Estimate the rate of sub-optimal CDK 4/6 inhibitor response (profile 3) in patients with metastatic hormone positive breast cancer in cycle 1 of CDK4/6 inhibitor and endocrine therapy in the first line setting.

II. Compare clinical benefit rate (CBR) in patients with sub-optimal (profile 3) and optimal (profiles 1 and 2) CDK4/6 inhibitor response after both cycles 1 and cycle 3.

III. Compare progression free survival (PFS) rates at 6 months (mo), 12 mo, 18 mo in patients with sub-optimal (profile 3) and optimal (profiles 1 and 2) CDK 4/6 inhibitor response after both cycles 1 and cycle 3.

IV. Assess CDK4/6 inhibitor response via TKa levels upon CDK4/6 inhibitor dose reductions or changes in CDK4/6 inhibitor regimens.

V. Compare CDK4/6 inhibitor response profiles across the three CDK 4/6 inhibitors among different patients and within the same patients if CDK4/6 inhibitor is changed throughout treatment course.

VI. Correlate TKa levels with tumor marker levels. VII. Assess plasma concentrations of CDK4/6 inhibitor drugs in patients with suboptimal TKa levels.

OUTLINE:

Patients undergo collection of blood samples per standard of care (SOC) on days 1, 15, and 28 of cycle 1, days 15 and 28 of cycle 2, days 15 and 28 of cycle 3, and day 28 of subsequent cycles for up to 12 cycles for analysis by DiviTum-TKa in the absence of disease progression or unacceptable toxicity.

After completion of study intervention, patients are followed up for 2 years.

Eligibility criteria: Inclusion Criteria:

* Participants must have histologically confirmed metastatic ER-positive (\> 10%), PR-positive or PR-negative, and HER2-negative (0 by immunohistochemistry \[IHC\] or if +1 or +2 by IHC, not amplified by fluorescence in situ hybridization \[FISH\]) breast cancer; ER positivity, PR positivity, and HER2 negativity as per the 2018 joint American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
* Participants must be starting CDK4/6 inhibitor and endocrine therapy as part of first-line therapy per standard of care and be previously CDK4/6 inhibitor-naïve.
* Participants must be enrolled prior to starting CDK4/6 inhibitor therapy.
* Participants must be ≥ 18 years of age.
* Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status \< 3.
* Willing and able to provide written informed consent for the trial.

Exclusion Criteria:

* Participants without evidence of metastatic disease prior to registration.
* Participants with prior use of CDK4/6 inhibitor therapy.
* Participants who are unable to provide informed consent for the trial.

Primary outcomes:
measure: Proportion of patients with thymidine kinase activity (TKa) values that switch from profile 3 to profile 1 or 2 after medication compliance and drug-drug interaction assessment
timeFrame: Immediately following counseling for medication compliance and adjustment of potential deleterious drug-drug interactions
measure: Rate of improvement in CDK4/6 inhibitor response (i.e. moving from profile 3 to profiles 1 or 2)
timeFrame: At day 28 of cycles 2 and 3 immediately following counselling for medication compliance and removing potential deleterious drug-drug interactions
Secondary outcomes:
measure: Clinical benefit rate (CBR) in patients with sub-optimal (profile 3) and optimal (profiles 1 and 2) CDK4/6 inhibitor response
timeFrame: At day 28 of cycles 1 and 3
measure: Progression free survival (PFS)
timeFrame: At 6, 12, and 18 months
measure: CDK4/6 inhibitor response via TKa levels upon CDK4/6 inhibitor dose reductions or changes in CDK4/6 inhibitor regimen due to adverse events
timeFrame: Up to 2 years
measure: Comparison of CDK4/6 inhibitor response profiles across the three CDK 4/6 inhibitors
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Derby
country: United States
facility: Smilow Cancer Hospital-Derby Care Center
state: Connecticut
city: Fairfield
country: United States
facility: Smilow Cancer Hospital Care Center-Fairfield
state: Connecticut
city: Glastonbury
country: United States
facility: Smilow Cancer Hospital Care Center at Glastonbury
state: Connecticut
city: Greenwich
country: United States
facility: Smilow Cancer Hospital Care Center at Greenwich
state: Connecticut
city: Guilford
country: United States
facility: Smilow Cancer Hospital Care Center - Guilford
state: Connecticut
city: Hamden
country: United States
facility: Smilow Cancer Hospital-Hamden Care Center
state: Connecticut
city: Hartford
country: United States
facility: Smilow Cancer Hospital Care Center at Saint Francis
state: Connecticut
city: New Haven
country: United States
facility: Smilow Cancer Center/Yale-New Haven Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale-New Haven Hospital Saint Raphael Campus
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: North Haven
country: United States
facility: Yale-New Haven Hospital North Haven Medical Center
state: Connecticut
city: Orange
country: United States
facility: Smilow Cancer Hospital-Orange Care Center
state: Connecticut
city: Stamford
country: United States
facility: Smilow Cancer Hospital Care Center at Long Ridge
state: Connecticut
city: Torrington
country: United States
facility: Smilow Cancer Hospital-Torrington Care Center
state: Connecticut
city: Trumbull
country: United States
facility: Smilow Cancer Hospital Care Center-Trumbull
state: Connecticut
city: Waterbury
country: United States
facility: Smilow Cancer Hospital-Waterbury Care Center
state: Connecticut
city: Waterford
country: United States
facility: Smilow Cancer Hospital Care Center - Waterford
state: Connecticut
city: Westerly
country: United States
facility: Smilow Cancer Hospital Care Center - Westerly
state: Rhode Island
Study officials:
affiliation: Yale University
name: Mariya Rozenblit
role: PRINCIPAL_INVESTIGATOR
References: