eligibility_summary
Adults ≥18 with HER2+ breast cancer and 1–10 new brain mets ≤3 cm, ECOG 0–2, life expectancy ≥12 wks, adequate marrow/liver/renal labs, prior systemic tx allowed except tucatinib/capecitabine, consent/contraception if applicable. Exclude: leptomeningeal mets, hemorrhage, lesions ≤5 mm of optic apparatus, GI diarrhea, cardiac disease, no MRI, HIV/HBV/HCV, tox >G1, comorbidity, recent trial tx, QTc ≥470 ms, LVEF <50%, strong CYP3A/2C8 modulators, allergy, corneal ulcer, pregnant/breastfeeding, no anthracyclines.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 1, single-arm trial evaluating stereotactic radiosurgery (SRS) plus three HER2-directed/chemotherapy agents for HER2-positive breast cancer brain metastases: 1) Tucatinib: oral small-molecule HER2 (ERBB2) tyrosine kinase inhibitor that blocks HER2 signaling. 2) Trastuzumab: IV humanized anti-HER2 IgG1 monoclonal antibody that inhibits HER2 receptor signaling and mediates ADCC. 3) Capecitabine: oral antimetabolite (prodrug of 5-FU) that inhibits thymidylate synthase, impairing DNA synthesis, can act as a radiosensitizer. Targets/pathways: HER2/ERBB2 on tumor cells and downstream PI3K/AKT and MAPK cascades, thymidylate synthase-dependent DNA synthesis, SRS induces tumor DNA double-strand breaks. Immune effector engagement via Fcγ receptor–bearing NK cells (ADCC).