AIM4 AI and Mechanistic Modeling in Molecular Medicine

To assess for potential pitfalls and to assess the feasibility of the approach of analysis of new tumor biopsies for selection of standard of care treatment selection in patients with metastatic hormone receptor positive breast cancer who have developed disease progression on 1st line endocrine therapy combined with a CDK4/6 inhibitor.

Study Overview

• Status: Withdrawn
• Conditions: Molecular Medicine
• Intervention / Treatment: Device: AI and mechanic modeling

Detailed Description

Primary Objective To assess the feasibility and utility of tumor evaluation to aid in selection of standard of care therapy for patients with hormone receptor positive (HR+) /HER2- advanced/metastatic breast cancer.

Secondary Objectives

• Accrual Rate (AR)
• Clinical Benefit Rate (CBR)
• To compare progression free survival (PFS) based on concordance with recommended treatment
• Duration of Response (DoR)
• Therapy Acceptance Rate (TAR)

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

MD Anderson Cancer Center

Description

Inclusion Criteria:

• Eligibility will be evaluated by the study team according to the following criteria. Subjects must meet all of the inclusion and none of the exclusion criteria to be registered to the study. Study treatment may not begin until a subject is registered.
• Patients must have histologically confirmed, advanced/unresectable stage III 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 CDK4/6 inhibitor (CDK4/6i) combination treatment with an aromatase inhibitor (AI) meeting one of the following criteria.
• Disease progression on treatment with a CDK4/6i and AI as 1st line endocrine therapy for advanced/metastatic breast cancer.
• Disease progression on or following treatment with a CDK4/6i in the adjuvant setting for early-stage breast cancer.
• Age ≥ 18 years.
• ECOG performance status of ≤2.
• Patient must have at least one lesion amenable to percutaneous core biopsy that is not a purely sclerotic bone lesion.
• Patient must have the ability to understand and the willingness to sign a written informed consent prior to registration on study.

Exclusion Criteria:

• Pregnant or lactating women.
• Prior treatment 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 and untreated, or active, brain or leptomeningeal metastases. Subjects with previously treated central nervous system (CNS) metastases may be enrolled in the study if they do not require systemic steroids, do not have seizures ort uncontrolled neurological symptoms, and have stable disease confirmed by radiographic assessment within at least 4 weeks prior to enrollment.
• History of malignancies other than adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥3 years.
• Platelet count < 100,000/microliter or INR >1.5.
• Life expectancy <1 year.
• Participants who are consented to participate in the clinical trial, who do not meet one or more criteria required for participation in the trial during the screening procedures, are considered screen failures. Records of participant screening to include screen failures will be maintained by the clinical research team. There is no role for re-evaluation and re-screening of patients once they have deemed to be a screen failure.
• Both men and women of all races and ethnic groups are eligible for this trial, although women comprise the majority of breast cancer patients and will be largely represented in this trial. Males are estimated to make up 1% of total breast cancer cases.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

AI and mechanic modeling; Participants with advanced/unresectable stage III or metastatic HR+ breast cancer with progression on a CDK4/6i and an AI will be eligible for study participation. The key action in this study will be the acquisition and analysis of tumor and blood for selection of standard of care systemic therapy. Tumor and blood will also be obtained at the time of disease progression to provide critical data for reverse translational model building. This will also provide insight into mechanisms of resistance for the administered standard of care therapy that can be used for future models to optimize selection of next-line therapy.

Device: AI and mechanic modeling; The data collected from research tests on your blood and tumor samples will be used to develop an AI model for treatment selection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and adverse events (AEs)	Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0	Through study completion; an average of 1 year.

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: Phase One Foundation
• Investigators: Principal Investigator: Azadeh Nasrazadani, MD,PHD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2024
• Primary Completion (Estimated): January 15, 2025
• Study Completion (Actual): January 15, 2025

Study Registration Dates

• First Submitted: July 30, 2024
• First Submitted That Met QC Criteria: July 30, 2024
• First Posted (Actual): August 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 2023-0886; NCI-2024-06520 (Other Identifier: NCI-CTRP Clinical Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No