NCT05977036 · Washington University School of Medicine
BettER: Biomarker Driven Early Therapeutic Selection in Patients With HR+ HER2- Metastatic or Unresectable Breast Cancer
What this study is about
This is a forward-looking 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.
View original scientific description
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.
Interventions
DEVICE
DiviTum® TKa assay
Will be utilized for determination of serum enzymatic activity of TK1 according to the manufacturer's instructions
DRUG
CDK4/6 + Endocrine therapy
FDA-approved endocrine therapy plus CDK4/6 inhibitor. Ribociclib is the preferred CDK4/6 inhibitor. In the event this drug cannot be obtained due to insurance authorization or if there are specific side effect profile concerns from the treating physician, an alternative CDK4/6 inhibitor is allowed.
Primary outcome measures
Progression-free survival (PFS) in patients who remain on CKD4/6i (patients with suppressed TKa levels at cycle 1 day 15)
Time frame: 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
Time frame: 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)
Time frame: 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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Diagnosis of metastatic or advanced unresectable invasive breast cancer that is hormone receptor-positive (HR+) and HER2-negative.
- Planned to initiate standard of care first-line therapy with FDA-approved endocrine therapy plus CDK4/6 inhibitor for the stated diagnosis at the time of study enrollment. Ribociclib is the preferred CDK4/6 inhibitor. In the event this drug cannot be obtained due to insurance authorization or if there are specific side effect profile concerns from the treating physician, an alternative CDK4/6 inhibitor is allowed.
- Any prior therapy for early stage breast cancer is allowed, including endocrine therapy and chemotherapy.
- Prior receipt of adjuvant CDK 4/6 inhibitor therapy is permitted provided therapy completion occurred \> 12 months prior to study enrollment.
- Presence of RECIST-evaluable disease. Patients with bone-only disease are eligible.
- At least 18 years of age.
- ECOG performance status ≤ 2
- Post-menopausal status, defined as one of the following:
- Age ≥ 60 years
- Age \< 60 with intact uterus and amenorrhea for 12 consecutive months or more
- Status post bilateral oophorectomy, total hysterectomy
- Pre- or peri-menopausal with suppressed ovarian function by use of GnRH agonist/antagonist or surgical bilateral oophorectomy
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion criteria
- Receipt of any prior cytotoxic chemotherapy line for metastatic disease. There will be no limit to chemotherapy use in the neoadjuvant or adjuvant setting.
- Patients with a prior or concurrent malignancy are excluded unless that malignancy's natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Concurrent participation in any investigational therapeutic trial for treatment of metastatic breast cancer. Eligibility Criteria - Physicians
- Medical Oncologist at Siteman Cancer Center.
- Treating patients with metastatic or advanced unresectable breast cancer.
- Willing to complete Physician Surveys during participation.
Where
- St Louis, Missouri
Collaborators
Biovica
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Dec 17, 2025 · Source of record for eligibility and locations