Functional Precision Oncology to Predict, Prevent, and Treat Early Metastatic Recurrence of TNBC

Phase 2

Recruiting

• Conditions: Breast Cancer Recurrent

• Registration Number: NCT05464082
• Lead Sponsor: University of Utah

Brief Summary

This is a prospective phase 2 study to use Functional Precision Oncology (FPO) to predict, prevent and treat early metastatic recurrence in subjects with HR-low/Her2 negative or triple negative breast cancer.

Detailed Description

The aim of this clinical trial is to extend the findings of the investigators' first observational clinical study titled "Towards personalized medicine: patient derived breast tumor grafts as predictors of relapse and response to therapy" (TOWARDS-I). In TOWARDS-II, the investigators will develop patient derived models (PDMs), comprising patient derived xenografts (PDXs) and organoids (PDO and PDxO), from patients newly diagnosed with local or locally advanced hormone receptor-low/Her2 negative or triple negative breast cancer. The investigators will prospectively evaluate the correlation between PDX engraftment with recurrence. Using PDMs, the investigators will perform genomic studies and functional drug screens (FPO). Upon disease recurrence, the investigators will return the results to the physician with the intent to inform treatment selection.

Study Timeline

• Study First Submitted: 2022-07-15
• Study First Submitted QC: 2022-07-18
• Study First Posted: 2022-07-19
• Study Start: 2023-01-06
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-03
• Last Update Posted: 2025-06-06
• Primary Completion: 2026-09-30
• Study Completion: 2028-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Proportion of cases where clinically actionable therapies were identified by FPO.	up to 3 years	Assess the feasibility and utility of Functional Precision Oncology (FPO) testing to identify therapies for patients with TNBC or HR-low/HER2- breast cancer who are at high risk of early recurrence
Compare the recurrence rates between patients whose tumors successfully engrafted in mice (PDX+) vs. not (PDX-)	Data will be assessed at 3-years from the time of definitive surgery.	Confirm that tumor engraftment as a PDX predicts early metastatic recurrence

Secondary Outcome Measures

Name	Time	Method
Correlation between tumor engraftment (PDX+/-) and relapse-free survival, overall survival, and response to preoperative chemotherapy and treatment response as assessed on the Residual Cancer Burden scale	up to 3 years	assess the correlation between PDX establishment and other clinical outcomes
Correlation between MHCII Immune Activation Score (high vs. low and as a continuous variable) and tumor engraftment (PDX+/-) and clinical outcomes (relapse-free and overall survival).	up to 3 years	determine the correlation between MHCII immune activation score and PDX engraftment
determine the feasibility of returning FPO results to inform the selection of 2nd line therapy after recurrence	up to 3 years	The proportion of cases where clinically actionable therapies are identified by FPO within 12 weeks of initiating 1st line therapy after recurrence. This endpoint is restricted to the subset of patients where clinically actionable therapies were not identified prior to time of recurrence
Proportion of cases where any type of patient derived models are successfully generated and clinically actionable therapies are identified by functional precision oncology.	up to 3 years	assess additional measures of feasibility and utility of Functional Precision Oncology
Correlation between methylated ctDNA measurements as assessed using the MethylPatch assay pretreatment, pre- and post surgery, with PDX engraftment data (+/-) and clinical outcomes (relapse-free and overall survival)	up to 3 years	determine if measurement of methylated ctDNA can strengthen predictions of recurrence when combined with PDX engraftment data
frequency with which therapeutic responses in PDX, PDxO, and/or PDO align with the clinical, radiographic, and pathologic responses observed in the matched patient	up to 3 years	determine the concordance between therapeutic responses in PDX, PDxO, and/or PDO and matched patient tumors
Calculate PFS ratios of 2nd line FPO-informed: 1st line "uninformed" therapy as a preliminary measure of efficacy	up to 3 years	assess the clinical efficacy of treatment decisions informed by FPO compared with treatment decisions not informed by FPO

Trial Locations

Locations (1)

Huntsman Cancer Institute at University of Utah; 🇺🇸 Salt Lake City, Utah, United States