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

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.

• Biopsy Procedure (Procedure), also known as Biopsy, BIOPSY_TYPE, Bx: Undergo tumor biopsy
• Biospecimen Collection (Procedure), also known as Biological Sample Collection, Biospecimen Collected, Specimen Collection: Undergo blood sample collection
• Bone Scan (Procedure), also known as Bone Scintigraphy: Undergo bone scan
• Computed Tomography (Procedure), also known as CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography: Undergo CT scan
• Electronic Health Record Review (Other): Ancillary studies
• Magnetic Resonance Imaging (Procedure), also known as Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI: Undergo MRI
• Positron Emission Tomography (Procedure), also known as Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT: Undergo PET scan
• Treatment Planning (Other): Receive tumor biology report with predicted ongoing response
• Treatment Regimen (Other), also known as Regimen, regimen or line of therapy, Regimen/Treatment Period/Vaccination Regimen, regimen_or_line_of_therapy, Treatment Protocol, Treatment Schedule: Receive treatment recommendations

Primary outcomes

• 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 outcomes

• Accrual rate [Up to 1 year]: Defined as is the number of patients enrolled over the period of a month.
• 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.
• Median progression free survival [From study registration to progression, symptomatic deterioration, or death due to any cause, up to 1 year]
• 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.

Sex: All, ages: 18 Years to any

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

• Irene M Kang, Principal investigator, City of Hope Medical Center

NIH grants: P30CA033572