Tka Assay for CDK4/6i
NCT Number: NCT06572800
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Anatomic Stage IV Breast Cancer AJCC v8|Metastatic HER2-Negative Breast Carcinoma
Interventions: DEVICE: DiviTum-TKa
Sponsor: Yale University
Collaborators: National Cancer Institute (NCI)
Sex: FEMALE
Age: ADULT, OLDER_ADULT
Enrollment: 50
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: SUPPORTIVE_CARE
Start Date: 2023-09-05
Completion Date: 2027-05-03
Locations: Smilow Cancer Hospital-Derby Care Center, Derby, Connecticut, 06418, United States|Smilow Cancer Hospital Care Center-Fairfield, Fairfield, Connecticut, 06824, United States|Smilow Cancer Hospital Care Center at Glastonbury, Glastonbury, Connecticut, 06033, United States|Smilow Cancer Hospital Care Center at Greenwich, Greenwich, Connecticut, 06830, United States|Smilow Cancer Hospital Care Center - Guilford, Guilford, Connecticut, 06437, United States|Smilow Cancer Hospital-Hamden Care Center, Hamden, Connecticut, 06518, United States|Smilow Cancer Hospital Care Center at Saint Francis, Hartford, Connecticut, 06105, United States|Smilow Cancer Center/Yale-New Haven Hospital, New Haven, Connecticut, 06510, United States|Yale-New Haven Hospital Saint Raphael Campus, New Haven, Connecticut, 06511, United States|Yale University, New Haven, Connecticut, 06520, United States|Yale-New Haven Hospital North Haven Medical Center, North Haven, Connecticut, 06473, United States|Smilow Cancer Hospital-Orange Care Center, Orange, Connecticut, 06477, United States|Smilow Cancer Hospital Care Center at Long Ridge, Stamford, Connecticut, 06902, United States|Smilow Cancer Hospital-Torrington Care Center, Torrington, Connecticut, 06790, United States|Smilow Cancer Hospital Care Center-Trumbull, Trumbull, Connecticut, 06611, United States|Smilow Cancer Hospital-Waterbury Care Center, Waterbury, Connecticut, 06708, United States|Smilow Cancer Hospital Care Center - Waterford, Waterford, Connecticut, 06385, United States|Smilow Cancer Hospital Care Center - Westerly, Westerly, Rhode Island, 02891, United States

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.

Primary Outcome Measures: 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 Outcome Measures: Clinical benefit rate (CBR) in patients with sub-optimal (profile 3) and optimal (profiles 1 and 2) CDK4/6 inhibitor response, CBR is defined as the total number of patients who achieve a complete response, partial response, or stable disease for 6 months or more from day 1 (D1) cycle 1 (C1). Comparisons between paired outcomes will be completed using the paired t-test or Wilcoxon signed-rank test for continuous parameters of interest, or McNemar's Chi-square test for categorical parameters of interest., At day 28 of cycles 1 and 3|Progression free survival (PFS), PFS is defined as the time from D1C1 to disease progression. Will be estimated using Kaplan-Meier method., 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, Will estimate the two-sided 95% exact CI using Clopper-Pearson method., Up to 2 years|Comparison of CDK4/6 inhibitor response profiles across the three CDK 4/6 inhibitors, Will be completed using the paired t-test or Wilcoxon signed-rank test for continuous parameters of interest, or McNemar's Chi-square test for categorical parameters of interest., Up to 2 years