Evaluating Biomarker Driven Early Therapeutic Selection in Patients With HR + HER2 - Metastatic or Unresectable Breast Cancer
This clinical trial evaluates the impact of biomarker driven early therapeutic selection of treatment in patients with hormone receptor positive (HR+) HER2 negative (-) breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or cannot be removed by surgery (unresectable). DiviTum (registered trademark) thymidine kinase activity (TKa), is a blood test that measures the enzyme, thymidine kinase, in the blood. The levels of this enzyme is higher when tumor cells are increasing. The DiviTum TKa may predict response to treatments and reduce radiation exposure, financial burden and anxiety in patients with metastatic or unresectable breast cancer.
Inclusion Criteria
- PATIENT: Diagnosis of metastatic or advanced unresectable invasive breast cancer with medical doctor (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 Food and Drug Administration (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
- PATIENT: Any prior therapy for early stage breast cancer is allowed, including endocrine therapy and chemotherapy
- PATIENT: 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
- PATIENT: Measureable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
- PATIENT: At least 18 years of age
- PATIENT: Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2
- PATIENT: 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 gonadotropin-releasing hormone (GnRH) agonist/antagonist or surgical bilateral oophorectomy
- PATIENT: Ability to understand and willingness to sign an institutional review board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable)
- PHYSICIAN: Medical oncologist at Siteman Cancer Center
- PHYSICIAN: Treating patients with metastatic or advanced unresectable breast cancer
- PHYSICIAN: Willing to complete physician surveys during participation
Exclusion Criteria
- Receipt of any prior cytotoxic chemotherapy line for metastatic disease. There is 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
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05977036.
Locations matching your search criteria
United States
Missouri
Saint Louis
PRIMARY OBJECTIVE:
I. Evaluate progression free survival (PFS) and clinical benefit rate (CBR) in patients with suppressed TKa levels at cycle 1 day 15 (C1D15) who remain on CDK4/6i (Arms 1 and 2, Cohort A) as well as PFS2 and CBR in patients who switch to an alternate therapy (Arms 1 and 2, Cohort B).
SECONDARY OBJECTIVES:
I. To evaluate the feasibility of early therapeutic switching in patients with metastatic hormone receptor positive (HR+) HER2- breast cancer on first- and second-line CDK4/6i (Arms 1 and 2, Cohorts B and C).
II. To evaluate the feasibility of delayed imaging in patients with suppressed TKa levels (Arm 1 Cohort A).
III. To evaluate the ability of baseline, C1D15, and C2D1 TKa levels in predicting clinical benefit, PFS, and overall survival (OS) on first-line or second-line CDK4/6i and later lines of therapy (all arms and cohorts).
IV. To evaluate if subsequent suppressed TKa levels in patients with suppressed TKa levels at C1D15 (Arms 1 and 2, Cohort A) would have a high likelihood predicting stable disease on subsequent staging scans within the 2 years of study period.
TERTIARY/EXPLORATORY OBJECTIVES:
I. To explore plasma- and tumor tissue-based biomarkers of CDK4/6i response and resistance (Arms 1 and 2, all cohorts).
II. To explore TKa dynamics (all arms and cohorts).
OUTLINE: Patients are assigned to 1 of 3 arms. Physicians are assigned to Arm IV.
ARM I: Patients receive standard of care (SOC) endocrine therapy and ribociclib or other CDK4/6 inhibitor and undergo blood sample collections at baseline and on C1D15. Patients with suppressed TKa levels at C1D15 are assigned to Cohort A. Patients with a lack of suppressed TKa levels at C1D15 are assigned to Cohort B and are assigned to Cohort C if they decide to remain on current therapy.
COHORT A: Patients continue to receive treatment in the absence of clinical progression. Patients undergo blood sample collections at day 1 of cycles 2 and 4, then every 3 months up to 24 months in the absence of clinical progression.
COHORT B: Patients receive a recommendation to switch to an alternative therapy. Patients then undergo blood sample collections at initiation of this second-line therapy and on the first day of subsequent cycles for up to 24 months in the absence of clinical progression.
COHORT C: Patients may continue to receive current treatment in the absence of clinical progression. Patients undergo blood sample collections at day 1 of cycles 2 and 4, then every 3 months up to 24 months in the absence of clinical progression.
Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) scans on study. Patients may also undergo bone scan or positron emission tomography (PET) scans on study.
ARM II: Patients receive SOC second-line endocrine therapy and ribociclib or other CDK4/6 inhibitor and undergo blood sample collections at baseline and on C1D15. Patients with suppressed TKa levels at C1D15 are assigned to Cohort A. Patients with a lack of suppressed TKa levels at C1D15 are assigned to Cohort B and are assigned to Cohort C if they decide to remain on current therapy.
COHORT A: Patients continue to receive treatment in the absence of clinical progression. Patients undergo blood sample collections at day 1 of cycles 2 and 4, then every 3 months up to 24 months in the absence of clinical progression.
COHORT B: Patients receive a recommendation to switch to an alternative therapy. Patients then undergo blood sample collections at initiation of this second-line therapy and on the first day of subsequent cycles for up to 24 months in the absence of clinical progression.
COHORT C: Patients may continue to receive current treatment in the absence of clinical progression. Patients undergo blood sample collections at day 1 of cycles 2 and 4, then every 3 months up to 24 months in the absence of clinical progression.
Patients also undergo CT or MRI scans on study. Patients may also undergo bone scan or PET scans on study.
ARM III: Patients receive alternative first- or second-line treatment in the absence of clinical progression. Patients undergo blood sample collections at day 1 of cycles 2 and 4, then every 3 months up to 24 months in the absence of clinical progression. Patients also undergo CT or MRI scans on study. Additionally, patients may undergo bone scan or PET scans on study.
ARM IV: Physicians complete surveys on study.
After completion of study intervention, patients are followed up every 6 months for 5 years.
Trial PhaseNo phase specified
Trial Typetreatment
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorKatherine Keaney Clifton
- Primary ID202307176
- Secondary IDsNCI-2023-08527
- ClinicalTrials.gov IDNCT05977036