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

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 hormone receptor (HR) positive, HER-2 negative metastatic or unresectable breast cancer receiving first-line or second-line treatment.

Conditions

Metastatic Breast Cancer

Unresectable Breast Cancer

Study ID

NCT05977036

Start date

Sep 25, 2024

Status verified date

Oct, 2026

Completion date

Sep 30, 2035

Anticipated

Primary completion date

Sep 30, 2035

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 with MD intent to treat as HR-positive and HER2-negative, with the following arm-specific requirements:

  • Arm 1: Patient must be planning 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. Note: Ribociclib is the preferred CDK4/6 inhibitor, but alternative CDK4/6 inhibitors are allowed. Note: Initiation of endocrine therapy prior to ultimate plan for addition of CDK4/6 inhibitor is permitted prior to enrollment.
  • Arm 2: patient must be planning to initiate standard of care second-line therapy with FDA-approved endocrine therapy plus CDK4/6 inhibitor for the stated diagnosis at the time of study enrollment. Triplet regimens are permitted as long as they contain CDK4/6 inhibitor and endocrine therapy. Note: Initiation of endocrine therapy prior to ultimate plan for addition of CDK4/6 inhibitor is permitted prior to enrollment.
  • Arm 3: patient must be planning to initiate first- or second-line therapy for the stated diagnosis at the time of study enrollment with therapy other than endocrine therapy plus CDK4/6 inhibitor.
  • 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 with the following arm-specific requirements:

  • Arm 1: CDK4/6 inhibitor may have been given only in the neoadjuvant/adjuvant setting (not metastatic setting), and the last dose must have been > 12 months prior to study enrollment.
  • Arms 2 and 3: No restrictions on prior CDK4/6 inhibitors.
  • Measurable or non-measurable disease per RECIST v1.1.
  • At least 18 years of age.
  • ECOG PS ≤ 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.
  • Prior or concurrent malignancy (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).
  • Arms 1 and 2: 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

145 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1 Cohort A: Suppressed TKa at Cycle 1 Day 15-continue 1st line treatment

  • Blood serum samples will be collected and analyzed using DiviTum® TKa prior to starting treatment, during treatment, and during follow-up as specified on the calendars.
  • Patients in Arm 1 with suppressed TKa (defined as ≤ 145 DuA) at C1D15 will be allocated into Cohort A, and the patient will continue on their CDK4/6i and endocrine therapy and undergo TKa draws at C2D1, C4D1, C7D1, and then approximately every 3 months. These patients may be given an option to delay imaging if TKa continues to be suppressed at coinciding TKa draw and imaging time points.

experimental: Arm 1 Cohort B: Lack of Tka suppression at Cycle 1 Day 15-switch to alternate therapy

  • Blood serum samples will be collected and analyzed using DiviTum® TKa prior to starting treatment, during treatment, and during follow-up as specified on the calendars.
  • Patients in Arm 1 with unsuppressed TKa (defined as >145 DuA) at C1D15 will be recommended to switch to an alternative therapy. Patients who do switch therapies will be allocated into Cohort B, and the patient will have TKa samples drawn at initiation of next-line therapy and on the first day of subsequent cycles, until progression or end of active participation (EOAP), whichever occurs first.

experimental: Arm 1 Cohort C: Lack of TKa suppression at Cycle 1 Day 15-remain on same 1st line treatment

  • Blood serum samples will be collected and analyzed using DiviTum® TKa prior to starting treatment, during treatment, and during follow-up as specified on the calendars.
  • Patients in Arm 1 with unsuppressed TKa (defined as >145 DuA) at C1D15 will be recommended to switch to an alternative therapy. Patients with unsuppressed TKa levels at C1D15 who do not switch therapies will be allocated into Cohort, and the patient will continue on their CDK4/6i and endocrine therapy and undergo TKa draws at C2D1, C4D1, C7D1, and then approximately every 3 months.

experimental: Arm 2 Cohort A: Suppressed TKa at Cycle 1 Day 15-continue 2nd line treatment

  • Blood serum samples will be collected and analyzed using DiviTum® TKa prior to starting treatment, during treatment, and during follow-up as specified on the calendars.
  • Patients in Arm 2 with suppressed TKa (defined as ≤ 145 DuA) at C1D15 will be allocated into Cohort A, and the patient will continue on their CDK4/6i and endocrine therapy and undergo TKa draws at C2D1, C4D1, C7D1, and then approximately every 3 months. These patients may be given an option to delay imaging if TKa continues to be suppressed at coinciding TKa draw and imaging time points.

experimental: Arm 2 Cohort B: Lack of Tka suppression at Cycle 1 Day 15-switch from 2nd line to alternate therapy

  • Blood serum samples will be collected and analyzed using DiviTum® TKa prior to starting treatment, during treatment, and during follow-up as specified on the calendars.
  • Patients in Arm 2 with unsuppressed TKa (defined as >145 DuA) at C1D15 will be recommended to switch to an alternative therapy. Patients who do switch therapies will be allocated into Cohort B, and the patient will have TKa samples drawn at initiation of next-line therapy and on the first day of subsequent cycles, until progression or end of active participation (EOAP), whichever occurs first.

experimental: Arm 2 Cohort C: Lack of TKa suppression at Cycle 1 Day 15-remain on same 2nd line treatment

  • Blood serum samples will be collected and analyzed using DiviTum® TKa prior to starting treatment, during treatment, and during follow-up as specified on the calendars.
  • Patients in Arm 2 with unsuppressed TKa (defined as >145 DuA) at C1D15 will be recommended to switch to an alternative therapy. Patients with unsuppressed TKa levels at C1D15 who do not switch therapies will be allocated into Cohort, and the patient will continue on their CDK4/6i and endocrine therapy and undergo TKa draws at C2D1, C4D1, C7D1, and then approximately every 3 months.

active comparator: Arm 3: Receiving 1st/2nd line treatment with any treatment other than CDK4/6i & endocrine therapy

Patients in Arm 3 will have TKa samples drawn at C2D1, C4D1, and every 3 months (+/- 2 weeks) thereafter (or at their physician's discretion), as well as at the time of clinical progression or end of active participation (EOAP), whichever occurs first. No recommendations for treatment or imaging will be made.

no intervention: Physicians

\- Physicians will be asked to complete surveys as follows:

  • Physician Survey 1 for patients in Arm 1 Cohort A who have the option increase the scan timing interval between the C4D1 and C7D1 scan.
  • Physician Survey 2 for patients in Arms 1 and 2, Cohorts B and C who have the option to switch to alternate therapy.

Interventions

DiviTum® TKa assay

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

Primary outcome measure

  • Progression-free survival (PFS) in patients who remain on CKD4/6i (Arms 1 and 2, Cohort A) [ Time Frame: Through completion of follow-up (estimated to be 7 years) ]
  • Clinical benefit rate (CBR) in patients who remain on CDK4/6i (Arms 1 and 2, Cohort A) [ Time Frame: Through completion of follow-up (estimated to be 7 years) ]
  • Progression-free survival (PFS2) in patients who switch to an alternate therapy (Arms 1 and 2, Cohort B) [ Time Frame: Through completion of follow-up (estimated to be 7 years) ]
  • Clinical benefit rate (CBR) in patients who switch to an alternate therapy (Arms 1 and 2, Cohort B) [ 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

Oct 9, 2026

Last verified

Oct, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by Washington University School of Medicine on 2026-10-09. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.