Anatomic Stage IV Breast Cancer AJCC v8, Metastatic HER2-Negative Breast Carcinoma
Conditions
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.
Interventions
DEVICEDiviTum-TKa
Analyze blood samples by DiviTum-TKa
Sponsors
National Cancer Institute (NCI)
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Immediately following counseling for medication compliance and adjustment of potential deleterious drug-drug interactions | Will be estimated using the two-sided 95% exact confidence interval (CI) using Clopper-Pearson method. |
| Rate of improvement in CDK4/6 inhibitor response (i.e. moving from profile 3 to profiles 1 or 2) | At day 28 of cycles 2 and 3 immediately following counselling for medication compliance and removing potential deleterious drug-drug interactions | Will be estimated using the two-sided 95% exact CI using Clopper-Pearson method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Progression free survival (PFS) | At 6, 12, and 18 months | PFS is defined as the time from D1C1 to disease progression. Will be estimated using Kaplan-Meier method. |
| 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 | Will estimate the two-sided 95% exact CI using Clopper-Pearson method. |
| Comparison of CDK4/6 inhibitor response profiles across the three CDK 4/6 inhibitors | Up to 2 years | 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. |
Countries
United States
Outcome results
None listed