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

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT07067138
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 120 Years
Healthy Volunteers
Not accepted

Interventions

  • Expression Networks for highLIGHting Tumor vulnerabilities (ENLIGHT) — DEVICE
    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.
  • TruSight(R) Oncology 500 — DEVICE
    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.
  • TruSeq Matched Tumor Normal Whole Exome Sequencing Assay — DEVICE
    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.

Study Details

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.

Key Dates

First listed
Jul 16, 2025
Start date
Feb 23, 2026
Status verified
Aug 2026
Primary completion
Aug 4, 2027
Completion
Aug 4, 2029

Study Design

Enrollment
175 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DEVICE_FEASIBILITY

Arms

  • Active Comparator: 1/No Recommended Match
    Treatment per physician's choice
  • Experimental: 2/Genomic Marker Associated with FDA-Approved On-Label Treatment
    Treatment in accordance with genomic marker; treatment to be directed locally by referring/treating physician
  • Experimental: 3/Transcriptomic Match
    Treatment regimen as selected by transcriptomic algorithm; treatment to be directed by NIH study team with requirement for treatment at NIH

Primary Outcome Measure

Part A: To assess the feasibility of using the ENLIGHT algorithm to match heavily pretreated participants with metastatic breast cancer to off-label therapies [ Time Frame: Assessed after the Reporting Visit of the 20th participant to the study, and to be completed before Part B ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892
National Cancer Institute Referral Office
[email protected]
888-624-1937

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Breast cancer
By specialty
OncologyBreast oncologyWomen's health
By research site
National Institutes of Health Clinical Center· Bethesda, MD

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