Tka Assay for CDK4/6i

NCT ID: NCT06572800

Last Updated: 2025-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-05
• Study Completion Date: 2025-09-16

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.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic HER2-Negative Breast Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Health services research (DiviTum-TKa)

Patients undergo collection of blood samples per 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.

Group Type: EXPERIMENTAL

DiviTum-TKa

Intervention Type: DEVICE

Analyze blood samples by DiviTum-TKa

Interventions

DiviTum-TKa

Analyze blood samples by DiviTum-TKa

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mariya Rozenblit

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, United States

Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut, United States

Smilow Cancer Hospital Care Center at Glastonbury

Glastonbury, Connecticut, United States

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, United States

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, United States

Smilow Cancer Hospital-Hamden Care Center

Hamden, Connecticut, United States

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, United States

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, United States

Yale-New Haven Hospital Saint Raphael Campus

New Haven, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, United States

Smilow Cancer Hospital-Orange Care Center

Orange, Connecticut, United States

Smilow Cancer Hospital Care Center at Long Ridge

Stamford, Connecticut, United States

Smilow Cancer Hospital-Torrington Care Center

Torrington, Connecticut, United States

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, United States

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, United States

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, United States

Smilow Cancer Hospital Care Center - Westerly

Westerly, Rhode Island, United States

Countries

United States

Other Identifiers

NCI-2024-01395

Identifier Type: REGISTRY

Identifier Source: secondary_id

2000033797

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA016359

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000033797

Identifier Type: -

Identifier Source: org_study_id