RecruitingNot ApplicableNCT07067138

A Synthetic Lethality-Focused Algorithm to Identify Therapeutic Options in Advanced Metastatic Breast Cancer (SYNTHESIS-Breast)

An Exploratory Study Using a Synthetic Lethality-Focused Algorithm to Identify Therapeutic Options in Advanced Metastatic Breast Cancer (SYNTHESIS-Breast)

Sponsor

National Cancer Institute (NCI)

Enrollment

175 participants

Start Date

Feb 23, 2026

Study Type

INTERVENTIONAL

Conditions

Breast Cancer Breast Carcinoma Cancer of the Breast Malignant Neoplasm of Breast

Summary

Background: Breast cancer is the most common cancer in US women. There are different types of breast cancers; some are aggressive and difficult to treat. Researchers want to know if an algorithm (ENLIGHT) can help choose approved drugs that will treat these cancers more effectively. Objective: To test whether ENLIGHT can find better treatments for aggressive breast cancers. Eligibility: People aged 18 years and older with triple-negative or endocrine therapy resistant breast cancer; the cancer must have either failed to respond to treatment or come back after treatment. Design: Participants will be screened. A sample of tissue taken from the tumor will be tested using ENLIGHT as well as another method (TruSight Oncology 500). Participants will be assigned to 1 of 3 groups based on the algorithm search results: Group 1: No drug option was recommended. Participants will continue with their standard treatment with their local doctors. Group 2: A drug already approved for the participant's disease was recommended, but the participant has not yet received it. These results will be sent to the participant's local doctors. Participants may return to the NIH if their disease gets worse after using the suggested drugs. Group 3: A drug approved for other uses was recommended. Participants will be treated with the recommended drugs at the NIH; their care will be managed by an NIH doctor. They will continue to receive treatment as long as the drugs are helping them. They will have follow-up visits for 2 years after treatment ends. Participants who are not treated at the NIH will be contacted for a check on their health every 3 months for 2 years.

Eligibility

Min Age: 18 YearsMax Age: 120 Years

Plain Language Summary

Simplified for easier understanding

This study at the NIH uses a specialized algorithm to match people with advanced metastatic breast cancer to off-label therapies (treatments approved for other cancers that may work based on the specific genetic makeup of their tumor) when standard options have been exhausted. **You may be eligible if...** - You are 18 or older and have confirmed metastatic breast cancer (hormone receptor positive, HER2-positive or -low, or triple-negative) - You have received at least one prior treatment for metastatic disease and your cancer has progressed or you cannot tolerate your current treatment - You have measurable disease on imaging - You have tumor tissue available from the past 6 months for genetic testing - Your blood counts and organ function are adequate **You may NOT be eligible if...** - Your cancer is in a visceral crisis (causing severe organ dysfunction) - You have active or symptomatic brain metastases needing immediate treatment - You are on continuous oxygen for lung disease or on dialysis - You are pregnant - Your biopsy tissue is not of sufficient quality for testing Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DEVICEExpression Networks for highLIGHting Tumor vulnerabilities (ENLIGHT)

This is a computational algorithm that takes RNA-seq data from tumor FFPE blocks and, given a list of pre-specified treatments, generates as output the predicted responses to those treatments.

DEVICETruSight(R) Oncology 500

TSO500 uses formalin-fixed, paraffin-embedded (FFPE) tumor blocks to generate a 523-gene DNA panel (with tumor mutational burden and microsatellite instability) to assess for biomarkers linked to FDA-approved, on-label therapies as well as whole-exome RNA-seq that can be used with the ENLIGHT algorithm.

DEVICETruSeq Matched Tumor Normal Whole Exome Sequencing Assay

The TruSeq Matched Tumor-Normal Whole Exome Sequencing assay is a next-generation sequencing assay that uses tumor DNA from formalin-fixed, paraffin-embedded (FFPE) tumor blocks and germline DNA drawn from blood to provide extended sequencing information on the tumor as well as any pathogenic variants, likely pathogenic variants, and variants of uncertain significance in 156 genes from the normal blood sample.