BettER: Biomarker Driven Early Therapeutic Selection in Patients With HR+ HER2- Metastatic or Unresectable Breast Cancer
- Conditions
- Metastatic Breast CancerUnresectable Breast Cancer
- Interventions
- Device: DiviTum® TKa assayDrug: CDK4/6 + Endocrine therapy
- Registration Number
- NCT05977036
- Lead Sponsor
- Washington University School of Medicine
- Brief Summary
This is a prospective study to assess the impact of biomarker driven, early therapeutic switching and delayed imaging with the incorporation of DiviTum® serum TK1 activity ("DiviTum® TKa") in patients with HR positive, HER-2 negative metastatic or unresectable breast cancer. Patients will receive first-line treatment with a CDK4/6 inhibitor (CDK4/6i) and endocrine therapy. All patients will have blood drawn for thymidine kinase activity (TKa) testing at baseline and at C1D15. Patients who are found to have a lack of TKa suppression at C1D15 will be recommended to switch to an alternative therapy. Patients with suppressed C1D15 TKa levels will continue on CDK4/6i and endocrine therapy until clinical progression. Patients with TKa which remains suppressed will be recommended to delay restaging scans from 24 weeks to 36 weeks.
The investigators hypothesize that a patient's TKa level at C1D15 is prognostic for progression-free survival (PFS) on a CDK4/6 inhibitor and early therapeutic switching in patients with a lack of C1D15 TKa suppression will be associated with prolonged PFS.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 65
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TKa suppressed at Cycle 1 Day 15 DiviTum® TKa assay * Study visits will occur at Baseline, Week 2 (C1D15), C2D1, C4D1, and clinical progression. Blood serum samples will be collected and analyzed using DiviTum® TKa at each of these dictated time points. * Patients with suppressed TKa levels at C1D15 will continue on CDK4/6i + endocrine therapy until clinical progression. There will be an option to elongate the time between restaging scans from Q3M to Q6M if TKa remains suppressed in this group. Physicians may repeat TKa in 2 weeks if TKa rise is noted and if TKa again becomes suppressed, may delay imaging. These patients will undergo TKa level monitoring at C2D1, C4D1, every 3 months thereafter, and at the time of clinical progression. The feasibility endpoint relates specifically to the Week 24 imaging time point. TKa suppressed at Cycle 1 Day 15 CDK4/6 + Endocrine therapy * Study visits will occur at Baseline, Week 2 (C1D15), C2D1, C4D1, and clinical progression. Blood serum samples will be collected and analyzed using DiviTum® TKa at each of these dictated time points. * Patients with suppressed TKa levels at C1D15 will continue on CDK4/6i + endocrine therapy until clinical progression. There will be an option to elongate the time between restaging scans from Q3M to Q6M if TKa remains suppressed in this group. Physicians may repeat TKa in 2 weeks if TKa rise is noted and if TKa again becomes suppressed, may delay imaging. These patients will undergo TKa level monitoring at C2D1, C4D1, every 3 months thereafter, and at the time of clinical progression. The feasibility endpoint relates specifically to the Week 24 imaging time point. TKa unsuppressed at Cycle 1 Day 15 DiviTum® TKa assay * Study visits will occur at Baseline, Week 2 (C1D15), C2D1, C4D1, and clinical progression. Blood serum samples will be collected and analyzed using DiviTum® TKa at each of these dictated time points. * Patients with lack of TKa suppression at C1D15 (defined as \>145 DuA) will be recommended to switch to an alternative therapy after compliance with the medication is ensured (by pill count) and potential drug-drug interactions are reviewed. These patients will have TKa samples drawn at initiation of second-line therapy and on the first day of subsequent cycles until progression. TKa unsuppressed at Cycle 1 Day 15 CDK4/6 + Endocrine therapy * Study visits will occur at Baseline, Week 2 (C1D15), C2D1, C4D1, and clinical progression. Blood serum samples will be collected and analyzed using DiviTum® TKa at each of these dictated time points. * Patients with lack of TKa suppression at C1D15 (defined as \>145 DuA) will be recommended to switch to an alternative therapy after compliance with the medication is ensured (by pill count) and potential drug-drug interactions are reviewed. These patients will have TKa samples drawn at initiation of second-line therapy and on the first day of subsequent cycles until progression.
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) in patients who remain on CKD4/6i (patients with suppressed TKa levels at cycle 1 day 15) Through completion of follow-up (estimated to be 7 years) . PFS in patients with suppressed TKa levels is defined as from the start date of receiving CDK4/6i to the end date of CDK4/6i or last date on CDK4/6i if the treatment on CDK4/6i is still ongoing or date of death if death occurs on treatment.
Clinical benefit rate (CBR) in patients who remain on CDK4/6i Through completion of follow-up (estimated to be 7 years) CBR is defined as total number (or percentage) of patients who achieved a complete response, partial response, or had stable disease for 6 months or more.
Progression-free survival (PFS) in patients who switch to an alternate therapy (patients with unsuppressed TKa levels at cycle 1 day 15) Through completion of follow-up (estimated to be 7 years) PFS in patients with unsuppressed TKa levels is defined as from the start date of receiving CDK4/6i to the end date of next-line therapy or last date on next-line if the treatment on next-line therapy is still ongoing or date of death if death occurs on treatment.
- Secondary Outcome Measures
Name Time Method Feasibility (compliance rate) in patients with suppressed TKa level at cycle 1 day 15 At 36 weeks -Feasibility defined as compliance rate:
\*\*Patients with suppressed TKa at C1D15, C2D1, C4D1 and 24 weeks: compliance is defined as this subset of physicians and patients who delay restaging scans from 24 weeks to 36 weeks.Feasibility (compliance rate) in patients with unsuppressed TKa level at cycle 1 day 15 At Cycle 1 Day 15 -Feasibility defined as compliance rate:
\*\*Patients with unsuppressed TKa at C1D15: compliance is defined as subset of physicians and patients following protocol recommendation to switch to next line of treatment.Baseline TKa level to predict overall survival (OS) on first-line CDK4/6i Through completion of follow-up (estimated to be 7 years) OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Baseline TKa level to predict overall survival (OS) on later lines of therapy Through completion of follow-up (estimated to be 7 years) OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Cycle 1 day 15 TKa level to predict overall survival (OS) on first-line CDK4/6i Through completion of follow-up (estimated to be 7 years) OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Cycle 1 day 15 TKa level to predict overall survival (OS) on later lines of therapy Through completion of follow-up (estimated to be 7 years) OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Cycle 2 day 1 TKa level to predict overall survival (OS) on first-line CDK4/6i Through completion of follow-up (estimated to be 7 years) OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Cycle 2 day 1 TKa level to predict overall survival (OS) on later lines of therapy Through completion of follow-up (estimated to be 7 years) OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Number of patients with TKa suppressed at cycle 1 day 15 who have stable disease on subsequent disease assessments Through 2 years
Trial Locations
- Locations (1)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States