Tka Assay for CDK4/6i

NCT06572800 | Completed DMC FDA Device

• 3 other identifiers: 2000033797NCI-2024-01395P30CA016359
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 18

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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

  Will be estimated using the two-sided 95% exact confidence interval (CI) using Clopper-Pearson method.

  Immediately following counseling for medication compliance and adjustment of potential deleterious drug-drug interactions

• Rate of improvement in CDK4/6 inhibitor response (i.e. moving from profile 3 to profiles 1 or 2)

  Will be estimated using the two-sided 95% exact CI using Clopper-Pearson method.

  At day 28 of cycles 2 and 3 immediately following counselling for medication compliance and removing potential deleterious drug-drug interactions

Secondary Outcomes (4)

• Clinical benefit rate (CBR) in patients with sub-optimal (profile 3) and optimal (profiles 1 and 2) CDK4/6 inhibitor response

  At day 28 of cycles 1 and 3

• Progression free survival (PFS)

  At 6, 12, and 18 months

• CDK4/6 inhibitor response via TKa levels upon CDK4/6 inhibitor dose reductions or changes in CDK4/6 inhibitor regimen due to adverse events

  Up to 2 years

• Comparison of CDK4/6 inhibitor response profiles across the three CDK 4/6 inhibitors

  Up to 2 years

Study Arms (1)

Health services research (DiviTum-TKa)

EXPERIMENTAL

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.

Device: DiviTum-TKa

Interventions

DiviTum-TKa DEVICE

Analyze blood samples by DiviTum-TKa

Health services research (DiviTum-TKa)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (18)

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, 06418, United States

Location

Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut, 06824, United States

Location

Smilow Cancer Hospital Care Center at Glastonbury

Glastonbury, Connecticut, 06033, United States

Location

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, 06830, United States

Location

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, 06437, United States

Location

Smilow Cancer Hospital-Hamden Care Center

Hamden, Connecticut, 06518, United States

Location

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105, United States

Location

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale-New Haven Hospital Saint Raphael Campus

New Haven, Connecticut, 06511, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, 06473, United States

Location

Smilow Cancer Hospital-Orange Care Center

Orange, Connecticut, 06477, United States

Location

Smilow Cancer Hospital Care Center at Long Ridge

Stamford, Connecticut, 06902, United States

Location

Smilow Cancer Hospital-Torrington Care Center

Torrington, Connecticut, 06790, United States

Location

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, 06611, United States

Location

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, 06708, United States

Location

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, 06385, United States

Location

Smilow Cancer Hospital Care Center - Westerly

Westerly, Rhode Island, 02891, United States

Location

Study Officials

• Mariya Rozenblit

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2024
• First Posted: August 27, 2024
• Study Start: September 5, 2023
• Primary Completion: September 16, 2025
• Study Completion: September 16, 2025
• Last Updated: October 8, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)