Actively Recruiting
A Synthetic Lethality-Focused Algorithm to Identify Therapeutic Options in Advanced Metastatic Breast Cancer (SYNTHESIS-Breast)
Led by National Cancer Institute (NCI) · Updated on 2026-04-30
175
Participants Needed
1
Research Sites
179 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
A Synthetic Lethality-Focused Algorithm to Identify Therapeutic Options in Advanced Metastatic Breast Cancer (SYNTHESIS-Breast)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically confirmed diagnosis of metastatic breast cancer
- Triple-negative breast cancer with estrogen receptor (ER) < 10% or progesterone receptor (PR) < 10% by immunohistochemistry (IHC)
- Endocrine-refractory hormone receptor positive breast cancer with ER >= 10% or PR >= 10% by IHC
- HER2-negative status as per ASCO-CAP guidelines, with HER2-low status considered per NCCN guidelines
- Treated with at least one line of systemic therapy after metastatic diagnosis with progressive disease or adverse events requiring discontinuation
- For hormone receptor positive, must be refractory to endocrine therapy as determined by clinical and study teams
- Measurable disease per RECIST v1.1
- Archival tumor tissue available from biopsy within past 6 months or ability to undergo biopsy
- Age 18 years or older
- ECOG performance status less than 2 (Karnofsky > 60%)
- Adequate organ and marrow function as defined by specified blood count and chemistry levels
- Ability to take oral medications
- Well-controlled diabetes or hypertension with at least annual physician follow-up
- Willingness to use contraception if assigned to therapy requiring it
- Willingness to comply with study procedures and visits
- Asymptomatic brain metastases treated locally at least 4 weeks prior with no need for additional therapy
- HIV patients on effective antiretroviral therapy with undetectable viral load for at least 6 months
- Participants with chronic hepatitis B on suppressive therapy with undetectable viral load
- Participants with treated and cured hepatitis C or currently on treatment with undetectable viral load
- Prior or concurrent malignancy allowed if not interfering with study assessments
- Cardiac function with New York Heart Association Functional Classification class 2B or better
- Ability and willingness to provide written informed consent
You will not qualify if you...
- Active visceral crisis, symptomatic brain metastases requiring local therapy, or active leptomeningeal disease
- Uncontrolled intercurrent illness that limits compliance or increases risk
- Active symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia
- Lung disease requiring continuous oxygen supplementation
- Decompensated cirrhosis or end-stage kidney disease on dialysis
- Positive pregnancy test at screening
- Inability to provide tissue specimens of sufficient quality for testing
- Poor quality of DNA or RNA from biopsy samples that cannot be corrected by re-biopsy
AI-Screening
AI-Powered Screening
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Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
Research Team
A
Ann C McCoy, R.N.
CONTACT
P
Padma S Rajagopal, M.D.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
DEVICE_FEASIBILITY
Number of Arms
3
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