Biology Guided Therapy Recommendations for Treatment Determination of Hormone Receptor-Positive Advanced, Unresectable or Metastatic Breast Cancer, ENDORSE Trial

Overview

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.

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.