Advanced Hormone Receptor-Positive Breast Carcinoma, Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Hormone Receptor-Positive Breast Carcinoma, Unresectable Hormone Receptor-Positive Breast Carcinoma
Conditions
Brief summary
This clinical trial tests the feasibility and utility of a biology guided therapy recommendations report to aid in determining treatment of hormone receptor positive breast cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). The biology guided therapy recommendations report is developed from testing a patients tumor tissue when they have progression to see what medications may work best and what medications the cancer may be resistant to based on their tumor biology. Patients and their doctor then receive that report with the suggested treatments. Receiving a biology guided therapy recommendations report may be a feasible and useable way to aid in treatment determination for hormone receptor positive advanced, unresectable or metastatic breast cancer.
Detailed description
PRIMARY OBJECTIVE: I. To assess the feasibility and utility of using a systems medicine approach to evaluate tumor tissue from patients with hormone receptor-positive HER2-negative unresectable metastatic breast cancer after progression on first line therapy to both predict estrogen dependence and aid in selection of effective standard of care therapy. SECONDARY OBJECTIVES: I. To determine the accrual rate (AR). II. To measure the clinical benefit rate (CBR). III. To compare progression free survival (PFS) based on concordance with recommended treatment. IV. To determine the duration of response (DoR). V. To measure the therapy acceptance rate (TAR). EXPLORATORY OBJECTIVES: I. To obtain additional genomic, epigenomic, and transcriptomic data on resistance mechanisms that informs future validation studies, artificial intelligence (AI) model-selected next line of therapy selection with anticipated highest efficacy amongst available options, and advanced AI model development. II. To assess obstacles to enrollment and pitfalls of the study design to guide future studies. OUTLINE: Patients have their tumor tissue analyzed. Their physician receives a report based on their tumor biology consisting of their predicted ongoing response to endocrine therapy, predicted ongoing response to endocrine therapy plus PIK3CA mutation or ESR1 mutation or HER2 mutation or mTOR sensitivity/resistance. The report includes treatment recommendations and the results of the specific tests completed on the tumor tissue. Physicians then determine a treatment regimen for the patient that may or may not include the treatment recommended in the report. Patients undergo blood sample collection and computed tomography (CT) scan or magnetic resonance imaging (MRI) and/or bone scan and/or positron emission tomography (PET) scan throughout the study. Patients may undergo tumor biopsy during screening and may optionally undergo at progression. After completion of study intervention, patients are followed every 3 months until disease progression.
Interventions
PROCEDUREBiopsy Procedure
Undergo tumor biopsy
PROCEDUREBiospecimen Collection
Undergo blood sample collection
PROCEDUREBone Scan
Undergo bone scan
PROCEDUREComputed Tomography
Undergo CT scan
OTHERElectronic Health Record Review
Ancillary studies
PROCEDUREMagnetic Resonance Imaging
Undergo MRI
PROCEDUREPositron Emission Tomography
Undergo PET scan
OTHERTreatment Planning
Receive tumor biology report with predicted ongoing response
OTHERTreatment Regimen
Receive treatment recommendations
Sponsors
City of Hope Medical Center
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must speak English * Documented informed consent of the participant and/or legally authorized representative. * Assent, when appropriate, will be obtained per institutional guidelines * Agreement to allow the use of archival tissue from diagnostic tumor biopsies * If unavailable, exceptions may be granted with study principal investigator (PI) approval * Age: ≥ 18 years * Patients must have histologically confirmed, unresectable or metastatic hormone receptor positive, HER2 breast cancer. Hormone receptor positive is defined as estrogen receptor \>= 10% and/or progesterone receptor \>= 10%. Her2 negative per American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines * Patient must have disease progression during or after prior endocrine therapy meeting one of the following criteria: * Disease progression on 1st line endocrine therapy for advanced/metastatic breast cancer. * Disease progression on or within 2 years of completion of treatment with a CDK4/6i in the adjuvant setting for early- stage breast cancer * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 * Patient must have at least one lesion amenable to percutaneous core * Clinically appropriate for biopsy
Exclusion criteria
* Prior treatment in the metastatic setting with capecitabine, phosphoinositide 3 kinase (PI3K) inhibitor, mechanistic target of rapamycin (mTOR) inhibitor, protein kinase B (Akt) inhibitor, selective estrogen receptor degrader (SERD), or HER2-targeted therapy, including neratinib * Known or untreated, or active, brain or leptomeningeal metastases that are deemed inappropriate to pursue therapy guided by systems medicine approach. Enrolled patients may receive radiation or other loco regional therapy prior to initiating systemic therapy on study. History of malignancies other than adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors not requiring active therapy * Life expectancy \< 1 year * Pregnant or breastfeeding * Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Turnaround time (feasibility) | Up to 30 days. | Report consists of an Evaluation of Novel Data-driven Outcomes via Response-guided Systems Medicine in Hormone Receptor-positive Advanced Breast Cancer (ENDORSE) signature score, MTOR signature score and status of other Food and Drug Administration approved biomarkers, including ESR1 mutations, PIK3CA mutations and HER2 mutation/expression). The turn-around time will be summarized by the range, mean, median, and standard deviation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of overall response | From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, up to 1 year | — |
| Therapy acceptance rate | Up to 1 year | Defined as the proportion of cases in which the recommended therapy by the study was the same as what was recommended by the physician. |
| Median progression free survival | From study registration to progression, symptomatic deterioration, or death due to any cause, up to 1 year | — |
| Clinical benefit rate | At 6 months | Will be summarized as the percentage of patients with complete response (CR), partial response (PR), or at least stable disease (SD) at 6 months. |
| Accrual rate | Up to 1 year | Defined as is the number of patients enrolled over the period of a month. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORIrene M Kang
City of Hope Medical Center
Outcome results
None listed