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High-Dose Methotrexate for Breast Cancer with Leptomeningeal Metastasis

This study is looking at how well high-dose methotrexate (HD-MTX) works for people with metastatic breast cancer that has spread to the leptomeninges (the membranes covering the brain and spinal cord). Specifically, it's for those with triple-negative, HER2-positive, or hormone-refractory breast cancer. You could join if you are an adult with this type of breast cancer and a good performance status. The study will give HD-MTX every two weeks until the disease gets worse or other reasons. The main goal is to see if patients live longer than 12 weeks. The study plans to enroll 16 participants, but its current status is unclear.

Study design
This is an interventional study, meaning participants receive a specific treatment. It plans to enroll 16 participants.
What's involved
Participants will receive high-dose methotrexate (HD-MTX) treatment every two weeks according to standard clinical practice until their disease progresses or they pass away.
Compensation
Not stated in the trial record.
Follow-up
The primary endpoint measures overall survival at 12 weeks. Secondary objectives include one-year survival and overall progression-free survival.

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NCT02422641

Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis

Recruiting
PHASE2Ages 18+InterventionalTreatment
Wake Forest University Health Sciences
~16 participants
Updated 2026-07-02 on ClinicalTrials.gov
What's tested:High-dose Methotrexate (8 gm/m2; HD-MTX)

At a glance

Recruiting sites
2 of 3 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall Survival (at 12 weeks)
Measured over 12 weeks

Conditions

Metastatic Breast Cancer
Leptomeningeal Disease

Explore related trials

Breast CarcinomaLeptomeningeal Disease

Where it's being run

3 sites across 3 states
Maryland1
Missouri1
North Carolina1

Study leadership

  • Roy Strowd, MD · PRINCIPAL_INVESTIGATOR · Wake Forest University Health Sciences

Who to contact

Sara Cox
[email protected]
336-713-7748
Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

Adults (male and female) age \>18
Eastern Cooperative Group (ECOG) Performance Scale 0-1 (see Appendix I)
Histologically or cytologically confirmed invasive breast cancer of the following subtype:
TRIPLE NEGATIVE (ER-negative, PR-negative, and HER2-negative disease). Triple-negative patients will be defined per ASCO-CAP Guidelines.
HER2-POSITIVE: HER2-positive patients will be defined per ASCO-CAP Guidelines.
HORMONE REFRACTORY: Patients with ER/PR-positive disease according to ASCO-CAP guidelines above may be considered if they have disease progression after two lines of hormonal therapy (administered in the adjuvant or metastatic setting), or are deemed clinically hormone-resistant taking into consideration the rate of progression of disease or a short interval of time on first line hormonal therapy before progression. Clinically hormone-resistant patients MUST also be discussed with the Study Chair, Study co-chair or designee in advance for approval.
Cytologic or unequivocal radiographic confirmation of leptomeningeal metastasis by dural puncture and/or neuroimaging with or without known brain metastasis
Adequate organ function as follows:

Exclusion

Prior allergy or adverse reaction to methotrexate
New York Heart Association Heart Failure Class \>3
Active diabetes insipidus
Active mucositis
Chemotherapy or stereotactic radiotherapy within the last 2 weeks
Partial brain radiotherapy (i.e. \<40% of total brain volume) within the last 2 weeks
Whole brain radiotherapy within the last 6 months or partial brain radiotherapy exceeding \>40% of total brain volume within the last 6 months
Prior treatment with any methotrexate containing systemic regimen within 1 year (excluding intrathecal methotrexate)
Concurrent or planned systemic chemotherapy, radiotherapy, new hormonal or anti- HER2 directed therapy directed at management of breast cancer (existing anti-HER2 therapy can be continued as recently recommended in the National Consensus Guidelines (26)
Uncontrolled or progressive systemic disease or other concurrent condition which in the Investigator's opinion makes HD-MTX an undesirable treatment option for the patient or would jeopardize compliance
Contraindication to MRI
Use of salicylates, non-steroidal anti-inflammatory drugs, or sulfonamide medications within one week of start of methotrexate
Pregnant women or women who are breastfeeding.
Patients with significant visceral fluid collections including ascites, pericardial effusions, pleural effusions or others may experience delayed clearance of methotrexate because of third space accumulation which could result in methotrexate toxicity and inability to tolerate the proposed study treatment. While these are not absolute exclusions the Study Chair or co-Chairs should be contacted to discuss possible enrollment. Patients with significant ascites defined as European Association for the Study of the Liver \> grade 2 (Appendix IV), or with asymptomatic pleural effusions with an estimated size \>200 mL, or with symptomatic pleural effusion of any size will be excluded.

What this trial measures

  • Overall Survival (at 12 weeks)12 weeks

    The primary endpoint is survival at 12 weeks from first date of treatment. For the primary analysis, this will be dichotomized according to whether the patient achieves an OS greater than 12 weeks (i.e. survival rate). This cutoff has been selected based on reported OS data in historical controls.