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

NCT ID: NCT05977036

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

65 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-25

Study Completion Date

2034-09-30

Brief Summary

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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

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Conditions

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Metastatic Breast Cancer Unresectable Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

DiviTum® TKa assay

Intervention Type DEVICE

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

CDK4/6 + Endocrine therapy

Intervention Type 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.

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.

Group Type EXPERIMENTAL

DiviTum® TKa assay

Intervention Type DEVICE

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

CDK4/6 + Endocrine therapy

Intervention Type 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.

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)

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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DiviTum® TKa assay

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

Intervention Type DEVICE

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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Biovica

UNKNOWN

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Katherine Clifton, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Katherine Clifton, M.D.

Role: CONTACT

314-273-3712

Facility Contacts

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Katherine Clifton, M.D.

Role: primary

314-273-3712

Related Links

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http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

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202307176

Identifier Type: -

Identifier Source: org_study_id