eligibility_summary
Inclusion: consent, ≥18, metastatic HER2+ breast cancer, leptomeningeal mets (MRI or CSF), ECOG 0–2, life ≥2 mo, stable steroids, CNS local therapy 2–8 wks prior allowed, adequate heme/liver/renal/cardiac, prior tox ≤G1, negative pregnancy test, contraception (nonhormonal if HR+). Exclusion: prior tucatinib/capecitabine, strong CYP2C8/3A4 meds, severe organ dysfunction, brivudine, curative anticoagulation, cerebrovascular disease, non‑off VP shunt, HIV/HBV/HCV, uncontrolled HTN/infection/resp failure, pregnancy/lactation, hypersensitivity (study drugs/5‑FU) or DPD deficiency, malabsorption, other cancer <5y, recent trial.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT05800275: Multicentric single-arm phase II testing tucatinib + capecitabine + intrathecal trastuzumab in HER2-amplified metastatic breast cancer with leptomeningeal metastases. Interventions/mechanisms: • Tucatinib (oral small-molecule HER2/ERBB2–selective tyrosine kinase inhibitor) blocks HER2 signaling, suppressing downstream MAPK/PI3K pathways. • Capecitabine (oral antimetabolite, prodrug of 5‑FU) inhibits thymidylate synthase, impairing DNA synthesis in proliferating tumor cells. • Trastuzumab (humanized monoclonal antibody) delivered intrathecally binds HER2, blocking receptor signaling and mediating ADCC within CSF. Targets: HER2-overexpressing breast cancer cells in the leptomeninges/CSF, HER2/ERBB2 signaling cascade (MAPK/PI3K) and nucleotide synthesis/DNA replication machinery. Primary aim: improve 12‑month overall survival.