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NCT Number: NCT05977036

BettER: Biomarker Driven Early Therapeutic Selection in Patients With HR+ HER2- Metastatic or Unresectable Breast Cancer

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.

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Key information

Conditions

Metastatic Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases Unresectable Breast Cancer

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location status: Recruiting

Location contact

Cynthia X Ma, M.D., Ph.D.

SUB_INVESTIGATOR

Jingqin (Rosy) Luo, Ph.D.

SUB_INVESTIGATOR

Katherine Clifton, M.D.

CONTACT

[email protected]

314-273-3712

Katherine Clifton, M.D.

PRINCIPAL_INVESTIGATOR

Kelly Bolton, M.D.

SUB_INVESTIGATOR

Mark Watson, M.D., Ph.D.

SUB_INVESTIGATOR

Nusayba Bagegni, M.D.

SUB_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

DiviTum® TKa assay

Device

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

CDK4/6 + Endocrine therapy

Drug

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 outcomes

  1. 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.

  2. 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.

  3. 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.

Secondary outcomes

  1. Feasibility (compliance rate) in patients with suppressed TKa level at cycle 1 day 15

    Time frame: 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.

  2. Feasibility (compliance rate) in patients with unsuppressed TKa level at cycle 1 day 15

    Time frame: 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.

  3. Baseline TKa level to predict overall survival (OS) on first-line CDK4/6i

    Time frame: 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.

  4. Baseline TKa level to predict overall survival (OS) on later lines of therapy

    Time frame: 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.

  5. Cycle 1 day 15 TKa level to predict overall survival (OS) on first-line CDK4/6i

    Time frame: 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.

  6. Cycle 1 day 15 TKa level to predict overall survival (OS) on later lines of therapy

    Time frame: 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.

  7. Cycle 2 day 1 TKa level to predict overall survival (OS) on first-line CDK4/6i

    Time frame: 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.

  8. Cycle 2 day 1 TKa level to predict overall survival (OS) on later lines of therapy

    Time frame: 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.

  9. Number of patients with TKa suppressed at cycle 1 day 15 who have stable disease on subsequent disease assessments

    Time frame: Through 2 years

Study contacts

Contact information is provided by the study sponsor or research team.

Katherine Clifton, M.D.

CONTACT

[email protected]

314-273-3712

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

  • Biovica

Registry information

Important dates

Study start
2024
Primary completion
2034
Study completion
2034
First posted
Aug 4, 2023
Registry last updated
Dec 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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