A prospective interventional trial at Wake Forest University Health Sciences is actively enrolling to assess systemic high-dose methotrexate (8 g/m²) in breast cancer subtypes complicated by leptomeningeal metastasis, including cases with concurrent brain parenchymal involvement.
Wake Forest University Health Sciences is conducting a Phase 2 prospective trial (NCT02422641) examining intravenous high-dose methotrexate (HD-MTX) at 8 g/m² in breast cancer patients who have developed leptomeningeal metastasis (LMD). The trial is currently recruiting and targets a population with limited therapeutic options and poor prognosis.
Eligible participants include those with triple-negative breast cancer (TNBC), HER2-positive disease, and hormone-refractory breast cancer—subtypes that collectively represent a high-risk cohort for CNS dissemination. Enrollment is open to individuals with or without concurrent brain parenchymal metastases, broadening the scope of the investigation to reflect the heterogeneous presentations seen in clinical practice.
Leptomeningeal disease in breast cancer carries a median survival measured in weeks to months with conventional approaches, and effective systemic CNS-penetrant regimens remain an unmet need. High-dose systemic methotrexate achieves cytotoxic concentrations in the cerebrospinal fluid, offering a rationale for its evaluation as an alternative or complement to intrathecal therapy. This trial aims to generate prospective efficacy and safety data to inform evidence-based management of this devastating complication.
Detailed eligibility criteria, primary endpoints, and interim results have not been publicly disclosed in the available source data. Clinicians should consult the full ClinicalTrials.gov record for enrollment requirements and protocol specifics.
Key points
- Phase 2 interventional trial (NCT02422641) is actively recruiting at Wake Forest University Health Sciences.
- HD-MTX is administered intravenously at 8 g/m²—a dose designed to achieve therapeutic CNS penetration.
- Eligible subtypes include triple-negative, HER2-positive, and hormone-refractory breast cancer with leptomeningeal metastasis.
- Participants with concurrent brain parenchymal involvement are also eligible, reflecting real-world disease complexity.
- Leptomeningeal metastasis in breast cancer represents a high unmet need with no established standard systemic regimen.
Why it matters
Leptomeningeal metastasis from breast cancer is associated with rapid neurological decline and very limited survival; prospective data on systemic HD-MTX could help establish an evidence-based CNS-penetrant treatment strategy for this population. Findings from this trial may be particularly relevant to neuro-oncologists and medical oncologists managing advanced HER2-positive or triple-negative breast cancer.