Recruiting

Biomarker Driven

Sponsor:

Washington University School of Medicine

Code:

NCT05977036

Conditions

Metastatic Breast Cancer

Unresectable Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

DiviTum® TKa assay

CDK4/6 + Endocrine therapy

Study Details

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.

Conditions

Metastatic Breast Cancer

Unresectable Breast Cancer

Study ID

NCT05977036

Start date

Sep 25, 2024

Status verified date

Dec, 2025

Completion date

Sep 30, 2034

Anticipated

Primary completion date

Sep 30, 2034

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria - Patients

  • 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 - Patients

  • 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.

Study Design

Enrollment

65 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: TKa suppressed at Cycle 1 Day 15

  • 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.

experimental: TKa unsuppressed at Cycle 1 Day 15

  • 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.

no intervention: Physicians

-Physicians will be asked to complete surveys as follows:

  • Physician Survey 1 for patients in the TKa C1D15 Suppressed group who have the option to delay the Week 24 scan at Week 24
  • Physician Survey 2 for patients in the TKa C1D15 Unsuppressed group at C1D15 (after TKa results have returned but before switching therapy)

Interventions

DiviTum® TKa assay

Will be utilized for determination of serum enzymatic activity of TK1 according to the manufacturer's instructions

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 measure

  • 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) ]
  • Clinical benefit rate (CBR) in patients who remain on CDK4/6i [ Time Frame: Through completion of follow-up (estimated to be 7 years) ]
  • 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) ]

Central Contacts and Locations

Central contacts

Katherine Clifton, M.D.

314-273-3712k.clifton@wustl.edu

Locations

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Katherine Clifton, M.D.

314-273-3712k.clifton@wustl.edu

Principal Investigator:

Katherine Clifton, M.D.

More Information

Sponsor

Washington University School of Medicine

Last update posted

Dec 17, 2025

Last verified

Dec, 2025

Keywords

  • ER+ HER2- metastatic breast cancer
  • biomarkers
  • thymidine kinase

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Washington University School of Medicine on 2025-12-17.