Metastatic Breast CancerPhase 2NCT02422641
Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis
A Phase 2 study testing High-dose Methotrexate (8 gm/m2; HD-MTX) in people with Metastatic Breast Cancer and Leptomeningeal Disease, run by Wake Forest University Health Sciences at 3 sites in United States.
Trial summary
This study is a prospective evaluation of systemic, intravenous high-dose methotrexate (HD-MTX, 8 g/m2) in patients with triple negative, HER2-positive, and hormone refractory breast cancer with leptomeningeal metastasis (LMD) with or without brain parenchymal involvement. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer, Leptomeningeal Disease
- What is being tested?
- High-dose Methotrexate (8 gm/m2; HD-MTX)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2015to Jul 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- NOTE: ASCO-CAP guidelines state that ER and PR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. HER2-positive is defined as HER2 IHC 3+, ISH ≥ 2.0, or average HER2 copy number ≥ 6.0 signals.
- NOTE: A patient who has a change in receptor status (e.g. PR negative to positive) may be stratified as triple negative or hormone positive, contrary to the most recent receptor testing, for the purposes of the study, based upon the clinical course at the discretion of 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:
- Estimated creatinine clearance >70 cc/min (calculated by Cockcroft-Gault formula) White blood cell counts >3000 cells/mcL Absolute neutrophil count >1500 cells/mcL Platelet count >100,000 cells/mcL Hematocrit >30% Serum bilirubin <1.5 x the ULN or <5x the ULN if secondary to liver metastasis Alanine aminotransferase or aspartate aminotransferase <2.5x the ULN or <5x the ULN if secondary to liver metastasis Alkaline phosphatase <2.5x the ULN or <5x the ULN if secondary to liver metastasis
- Able to provide confirmed consent
Who cannot join
- 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
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- 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.
- NOTE: Systemic staging of the chest/abdomen/pelvis is required for study entry. See Sections 8.1.9. Body fluid will be assessed based on this study.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Strowd Roy, MD contact
United States3 sites, 2 recruiting
- Recruiting
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Joy Fisher, jfisher@jhmi.edu
- Active, not recruiting
Siteman Cancer Center- Washington University School of Medicine in St. Louis
St Louis, Missouri, 63130
- Recruiting
Comprehensive Cancer Center at Wake Forest University (CCCWFU)
Winston-Salem, North Carolina, 27157
Roy Strowd, MD, rstrowd@wakehealth.edu
About this study
Official title: Traditional Incision and Drainage of Cutaneous Abscess Vs. Minimally Invasive Incision and Drainage With Vessel Loop: A Randomized Controlled Trail
This study is a prospective evaluation of systemic, intravenous high-dose methotrexate (HD-MTX, 8 g/m2) in patients with triple negative, HER2-positive, and hormone refractory breast cancer with leptomeningeal metastasis (LMD) with or without brain parenchymal involvement.
Read the detailed description
Primary Objective:
- To assess if treatment with systemic intravenous high-dose methotrexate (HD-MTX) will result in an overall survival (OS) exceeding 12 weeks at 80% among patients with triple negative, HER2-positive, and hormone refractory metastatic breast cancer patients with leptomeningeal metastasis (LMD) with and without parenchymal brain involvement.
Secondary and Exploratory Objectives
- To describe the one-year survival in patients with LMD from metastatic breast cancer treated with HD-MTX.
- To describe the overall progression free survival (PFS) in patients with LMD from metastatic breast cancer treated with HD-MTX.
- To describe the tolerability of HD-MTX in patients with LMD from metastatic breast cancer.
- To describe the cost of HD-MTX treatment in patients with LMD from metastatic breast cancer.
- To investigate cytologic sterilization following HD-MTX in patients with LMD from metastatic breast cancer.
- Conditions
- Metastatic Breast Cancer, Leptomeningeal Disease
- Being tested
- High-dose Methotrexate (8 gm/m2; HD-MTX)
- Medical subject headings
- Breast Neoplasms, Meningeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-dose Methotrexate (8 gm/m2; HD-MTX)Drug
Enrolled patients will undergo treatment with HD-MTX (8 g/m2) as per current standard practice on an every 2 week schedule until disease progression or death from any cause. Treatment will be performed according to standard clinical practice. Surveillance imaging with or without cytologic evaluation will be performed as per standard clinical practice after every 2 cycles (~28 days). Treatment will continue until there is unequivocal evidence of clinical or radiographic CNS or systemic disease progression, death from any cause, or intolerance.
| Study group | Role | What they receive |
|---|---|---|
| High-dose Methotrexate (8 gm/m2; HD-MTX) | Experimental | Enrolled patients will undergo treatment with HD-MTX (8 g/m2) as per current standard practice on an every 2 week schedule until disease progression or death from any cause. Treatment will be performed according to standard clinical practice. Surveillance imaging with or without cytologic evaluation will be performed as per standard clinical practice after every 2 cycles (~28 days). Treatment will continue until there is unequivocal evidence of clinical or radiographic CNS or systemic disease progression, death from any cause, or intolerance. Receives: Drug: High-dose Methotrexate (8 gm/m2; HD-MTX) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (at 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.
Measured: 12 weeks
Secondary outcomes (5)
One year survival
As defined as the proportion of patients with time to death greater than 12 months from the time of first date of treatment.
Measured: 1 year
Progression Free Survival
Progression free survival as defined as the time from first date of treatment to the time of systemic or neurologic progression of disease whichever occurs first. Neurologic progression will be defined as the minimum of clinical or radiographic progression. Clinical neurologic progression will be defined by neurologic examination demonstrating objective, new neurologic deficit attributable to the underlying LMD. Radiographic progression (neurologic or systemic) will be defined by RECIST criteria.
Measured: From date of first treatment to the time of systemic or neurologic progression of disease whichever occurs first, assessed up to 2 years
Tolerability of Treatment - Number of Grade 3 or Higher Adverse Events
Toxicity as grade 3 and higher will be tabulated by reporting period, where reporting period is defined to be the planned 14 day period between administrations of high-dose methotrexate (HD MTX).
Measured: Up to 2 years
Number of Treatment Delays
Toxicities related to dose delays will be recorded by reporting period, where reporting period is defined to be the planned 14 day period between administrations of HD MTX. The number of times treatment is delayed divided by the number of reporting periods administered to all patients on study will be used to characterize the fraction of times treatments must be delayed.
Measured: Up to 2 years
Number of Dose Reductions
Toxicities related to dose delays will be recorded by reporting period, where reporting period is defined to be the planned 14 day period between administrations of HD MTX. The number of times treatment is delayed divided by the number of reporting periods administered to all patients on study will be used to characterize the fraction of times treatments must be delayed.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2015 (estimated)
- Study startMay 2015
- Primary completionDec 2026 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Roy Strowd, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02422641
- Sponsor's protocol ID
- IRB00035551
- Other IDs
- P30CA012197, CCCWFU 74315
- Status last verified
- Oct 2026
- First submitted
- 10 Apr 2015
- Last updated
- 27 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Traditional Incision and Drainage of Cutaneous Abscess Vs. Minimally Invasive Incision and Drainage With Vessel Loop: A Randomized Controlled Trail
- ClinicalTrials.gov ID
- NCT02422641
- Acronym / sponsor ID
- IRB00035551
- Conditions
- Metastatic Breast Cancer, Leptomeningeal Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, National Cancer Institute (NCI)
- Study start
- May 2015
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Jul 2027 (estimated)
- First posted
- 21 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a prospective evaluation of systemic, intravenous high-dose methotrexate (HD-MTX, 8 g/m2) in patients with triple negative, HER2-positive, and hormone refractory breast cancer with leptomeningeal metastasis (LMD) with or without brain parenchymal involvement.
Detailed description
Primary Objective:
- To assess if treatment with systemic intravenous high-dose methotrexate (HD-MTX) will result in an overall survival (OS) exceeding 12 weeks at 80% among patients with triple negative, HER2-positive, and hormone refractory metastatic breast cancer patients with leptomeningeal metastasis (LMD) with and without parenchymal brain involvement.
Secondary and Exploratory Objectives
- To describe the one-year survival in patients with LMD from metastatic breast cancer treated with HD-MTX.
- To describe the overall progression free survival (PFS) in patients with LMD from metastatic breast cancer treated with HD-MTX.
- To describe the tolerability of HD-MTX in patients with LMD from metastatic breast cancer.
- To describe the cost of HD-MTX treatment in patients with LMD from metastatic breast cancer.
- To investigate cytologic sterilization following HD-MTX in patients with LMD from metastatic breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| High-dose Methotrexate (8 gm/m2; HD-MTX) | Experimental | Drug: High-dose Methotrexate (8 gm/m2; HD-MTX)Enrolled patients will undergo treatment with HD-MTX (8 g/m2) as per current standard practice on an every 2 week schedule until disease progression or death from any cause. Treatment will be performed according to standard clinical practice. Surveillance imaging with or without cytologic evaluation will be performed as per standard clinical practice after every 2 cycles (~28 days). Treatment will continue until there is unequivocal evidence of clinical or radiographic CNS or systemic disease progression, death from any cause, or intolerance. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High-dose Methotrexate (8 gm/m2; HD-MTX)Enrolled patients will undergo treatment with HD-MTX (8 g/m2) as per current standard practice on an every 2 week schedule until disease progression or death from any cause. Treatment will be performed according to standard clinical practice. Surveillance imaging with or without cytologic evaluation will be performed as per standard clinical practice after every 2 cycles (~28 days). Treatment will continue until there is unequivocal evidence of clinical or radiographic CNS or systemic disease progression, death from any cause, or intolerance. | Drug | High-dose Methotrexate (8 gm/m2; HD-MTX) |
Primary outcome
Overall Survival (at 12 weeks)
Time frame: 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.
5 secondary outcomes
One year survival
Time frame: 1 year
Progression Free Survival
Time frame: From date of first treatment to the time of systemic or neurologic progression of disease whichever occurs first, assessed up to 2 years
Tolerability of Treatment - Number of Grade 3 or Higher Adverse Events
Time frame: Up to 2 years
Number of Treatment Delays
Time frame: Up to 2 years
Number of Dose Reductions
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Strowd Roy, MD contact
Roy Strowd, MD principal investigator
Wake Forest University Health Sciences
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing High-dose Methotrexate (8 gm/m2; HD-MTX) in people with Metastatic Breast Cancer and Leptomeningeal Disease, run by Wake Forest University Health Sciences at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sara Cox (336-713-7748, Sara.Cox@advocatehealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (at 12 weeks) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.