NCT07067138
A Synthetic Lethality-Focused Algorithm to Identify Therapeutic Options in Advanced Metastatic Breast Cancer (SYNTHESIS-Breast)
Recruiting
NAAges 18+InterventionalDevice feasibilityNational Cancer Institute (NCI)Government-funded
~175 participants
Updated 2026-08-21 on ClinicalTrials.gov
What's tested:Expression Networks for highLIGHting Tumor vulnerabilities (ENLIGHT)TruSight(R) Oncology 500TruSeq Matched Tumor Normal Whole Exome Sequencing Assay
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Part A: To assess the feasibility of using the ENLIGHT algorithm to match heavily pretreated participants with metastatic breast cancer to off-label therapies
Measured over Assessed after the Reporting Visit of the 20th participant to the study, and to be completed before Part B
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesMaryland1
Study leadership
- Stanley Lipkowitz, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
TNBC Cohort: TNBC will be defined as ER \< 10% or PR \< 10% by immunohistochemistry (IHC).
Endocrine-Refractory Cohort: HR+ (ER+ and/or PR+) will be defined as ER \>= 10% or PR \>= 10% by IHC.
For both cohorts, HER2 will be considered negative if not amplified as per ASCOCAP guidelines per IHC/FISH. Note: HER2-low status will be regarded in accordance with NCCN guidelines (in which this designation serves as a predictive marker for trastuzumab deruxtecan, but participants are otherwise not considered eligible for other HER2-directed therapies). 3. Participants must have been treated with at least one (1) line of systemic therapy after diagnosis of metastatic disease, anticipate or have progressive disease or adverse events requiring discontinuation of their current regimen, and must not be able to transition to another approved systemic therapy shown to improve overall survival.
Participants with HR+ disease must be deemed refractory to endocrine therapy per their clinical team, with concordance by study team.
Hemoglobin \>= 8g/dL
Absolute neutrophil count \>= 1,200/mcL
Platelets \>=75,000/mcL
Total bilirubin \<= 1.5 x institutional upper limit of normal (In the case of known Gilbert's Disease, total bili \>1.5 may be considered.)
AST(SGOT)/ALT(SGPT) \<= 3x institutional upper limit of normal
Creatinine \< 1.5 x normal institutional limits OR Creatinine clearance \>=30 mL/min/1.73 m2 9. Ability to take oral medications. 10. Participants with an existing diagnosis of diabetes or hypertension, must have disease well-controlled with at least annual physician follow-up. 11. Women of child-bearing potential and men with a partner of child-bearing potential must be willing to use appropriate contraception in the event that they match to a therapy that requires such. The duration of contraception use will depend on the therapy assigned. 12. Willingness to comply with required study procedures and visits for the duration of study. 13. Participants with asymptomatic brain metastases may be included if metastases have been previously treated with local therapy including radiation at least 4 weeks prior to first dose of treatment and there is no indication for additional local therapy (including active progression). 14. Participants with human immunodeficiency virus (HIV) must be on an effective anti-retroviral therapy with undetectable viral load for at least the last 6 months. 15. Participants with evidence of chronic hepatitis B virus (HBV) infection, must have HBV viral load that is undetectable on suppressive therapy, if indicated. 16. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection must be currently on treatment, with undetectable HCV viral load. 17. Participants with a prior or concurrent malignancy are eligible if the natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the off-label therapies offered on this study in the opinion of the Principal Investigator (PI) and are otherwise eligible for this trial. 18. Participants with current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. Note: To be eligible for this trial, participants should be class 2B or better. 19. Ability of participant to understand and the willingness to sign a written informed consent document.
What this trial measures
- Part A: To assess the feasibility of using the ENLIGHT algorithm to match heavily pretreated participants with metastatic breast cancer to off-label therapiesAssessed after the Reporting Visit of the 20th participant to the study, and to be completed before Part B
The number of participants of the first 20 enrolled overall having a match via ENLIGHT and being assigned to Arm 3.
- Part B: (If feasibility lead-in met) To assess the objective response rate (ORR) of participants with advanced breast cancer using treatment recommended by the ENLIGHT algorithmEvery 2 cycles until progression of disease, completion of treatment, or 2 years after treatment initiation (whichever comes first)
ORR is reported as a single endpoint measure (percentage) at time of interim analysis and at time of study completion and will be accompanied by a 95% confidence interval.