search
Back to results

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

Primary Purpose

Metastatic Breast Cancer, Unresectable Breast Cancer

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
DiviTum® TKa assay
CDK4/6 + Endocrine therapy
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring ER+ HER2- metastatic breast cancer, biomarkers, thymidine kinase

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

No Intervention

Arm Label

TKa suppressed at Cycle 1 Day 15

TKa unsuppressed at Cycle 1 Day 15

Physicians

Arm Description

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.

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.

-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)

Outcomes

Primary Outcome Measures

Progression-free survival (PFS) in patients who remain on CKD4/6i (patients with suppressed TKa levels at cycle 1 day 15)
. 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
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)
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 Outcome Measures

Feasibility (compliance rate) in patients with suppressed TKa level at cycle 1 day 15
-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.
Feasibility (compliance rate) in patients with unsuppressed TKa level 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.
Baseline TKa level to predict overall survival (OS) on first-line CDK4/6i
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Baseline TKa level to predict overall survival (OS) on later lines of therapy
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Cycle 1 day 15 TKa level to predict overall survival (OS) on first-line CDK4/6i
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Cycle 1 day 15 TKa level to predict overall survival (OS) on later lines of therapy
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Cycle 2 day 1 TKa level to predict overall survival (OS) on first-line CDK4/6i
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Cycle 2 day 1 TKa level to predict overall survival (OS) on later lines of therapy
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Number of patients with TKa suppressed at cycle 1 day 15 who have stable disease on subsequent disease assessments

Full Information

First Posted
July 27, 2023
Last Updated
October 2, 2023
Sponsor
Washington University School of Medicine
Collaborators
Biovica
search

1. Study Identification

Unique Protocol Identification Number
NCT05977036
Brief Title
BettER: Biomarker Driven Early Therapeutic Selection in Patients With HR+ HER2- Metastatic or Unresectable Breast Cancer
Official Title
BettER: Biomarker Driven Early Therapeutic Selection in Patients With HR+ HER2- Metastatic or Unresectable Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 30, 2023 (Anticipated)
Primary Completion Date
November 30, 2033 (Anticipated)
Study Completion Date
November 30, 2033 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
Biovica

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer, Unresectable Breast Cancer
Keywords
ER+ HER2- metastatic breast cancer, biomarkers, thymidine kinase

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
65 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TKa suppressed at Cycle 1 Day 15
Arm Type
Experimental
Arm Description
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.
Arm Title
TKa unsuppressed at Cycle 1 Day 15
Arm Type
Experimental
Arm Description
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.
Arm Title
Physicians
Arm Type
No Intervention
Arm Description
-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)
Intervention Type
Device
Intervention Name(s)
DiviTum® TKa assay
Intervention Description
Will be utilized for determination of serum enzymatic activity of TK1 according to the manufacturer's instructions
Intervention Type
Drug
Intervention Name(s)
CDK4/6 + Endocrine therapy
Intervention Description
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 Information:
Title
Progression-free survival (PFS) in patients who remain on CKD4/6i (patients with suppressed TKa levels at cycle 1 day 15)
Description
. 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.
Time Frame
Through completion of follow-up (estimated to be 7 years)
Title
Clinical benefit rate (CBR) in patients who remain on CDK4/6i
Description
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.
Time Frame
Through completion of follow-up (estimated to be 7 years)
Title
Progression-free survival (PFS) in patients who switch to an alternate therapy (patients with unsuppressed TKa levels at cycle 1 day 15)
Description
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.
Time Frame
Through completion of follow-up (estimated to be 7 years)
Secondary Outcome Measure Information:
Title
Feasibility (compliance rate) in patients with suppressed TKa level at cycle 1 day 15
Description
-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.
Time Frame
At 36 weeks
Title
Feasibility (compliance rate) in patients with unsuppressed TKa level at cycle 1 day 15
Description
-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.
Time Frame
At Cycle 1 Day 15
Title
Baseline TKa level to predict overall survival (OS) on first-line CDK4/6i
Description
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Time Frame
Through completion of follow-up (estimated to be 7 years)
Title
Baseline TKa level to predict overall survival (OS) on later lines of therapy
Description
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Time Frame
Through completion of follow-up (estimated to be 7 years)
Title
Cycle 1 day 15 TKa level to predict overall survival (OS) on first-line CDK4/6i
Description
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Time Frame
Through completion of follow-up (estimated to be 7 years)
Title
Cycle 1 day 15 TKa level to predict overall survival (OS) on later lines of therapy
Description
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Time Frame
Through completion of follow-up (estimated to be 7 years)
Title
Cycle 2 day 1 TKa level to predict overall survival (OS) on first-line CDK4/6i
Description
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Time Frame
Through completion of follow-up (estimated to be 7 years)
Title
Cycle 2 day 1 TKa level to predict overall survival (OS) on later lines of therapy
Description
OS is defined as from the start date of receiving CDK4/6i to the date of death or date of last follow up.
Time Frame
Through completion of follow-up (estimated to be 7 years)
Title
Number of patients with TKa suppressed at cycle 1 day 15 who have stable disease on subsequent disease assessments
Time Frame
Through 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Katherine Clifton, M.D.
Phone
314-273-3712
Email
k.clifton@wustl.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katherine Clifton, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katherine Clifton, M.D.
Phone
314-273-3712
Email
k.clifton@wustl.edu
First Name & Middle Initial & Last Name & Degree
Katherine Clifton, M.D.
First Name & Middle Initial & Last Name & Degree
Cynthia X Ma, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Mark Watson, M.D., Ph.D.
First Name & Middle Initial & Last Name & Degree
Jingqin Rosy Luo, Ph.D.

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

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

We'll reach out to this number within 24 hrs