RECRUITING

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

Conditions

Metastatic Breast Cancer Leptomeningeal Disease

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Management of leptomeningeal disease (LMD) in patients with metastatic breast cancer is an area of unmet clinical need. High-dose methotrexate (HD-MTX) is known to have activity against breast cancer and in contrast to other systemic chemotherapeutics, it penetrates the blood brain barrier, targets areas of poor cerebrospinal fluid flow, may penetrate bulky leptomeningeal disease, and provide treatment to systemic disease burden. While two retrospective studies have suggested activity of HD-MTX in LMD in patients with breast cancer, no prospective data are available to inform its inclusion in treatment regimens. Thus, while HD-MTX is included in the NCCN Guidelines for LMD and while it is used to varying degrees in cancer centers across the nation, this is more representative of the lack of available therapies for LMD as opposed to strong evidence-based data. This phase II, prospective study will evaluate systemic, intravenous HD-MTX in breast cancer patients with leptomeningeal metastasis with or without brain parenchymal metastasis.

Official Title

Traditional Incision and Drainage of Cutaneous Abscess Vs. Minimally Invasive Incision and Drainage With Vessel Loop: A Randomized Controlled Trail

Quick Facts

Study Start:2015-05

Study Completion:2027-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT02422641

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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 (American Society of Clinical Oncology-College of American Pathologists). * 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 investigator, co-investigator 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 * Alanine aminotransferase or aspartate aminotransferase \<2.5x the ULN * Alkaline phosphatase \<2.5x the ULN or \<5x the ULN if secondary to liver metastasis * Able to provide confirmed consent	* Prior allergy or adverse reaction to methotrexate * New York Heart Association Heart Failure Class \>3 (see Appendix II) * Active diabetes insipidus * Active mucositis * Chemotherapy or stereotactic radiotherapy within the last 2 weeks * Partial brain radiotherapy (i.e., less than or equal to 40% of total brain volume) within the last two weeks * Whole brain radiotherapy within the last 6 months or partial brain radiotherapy exceeding greater than 40% of total brain volume in 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 * 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 investigators or co-investigators should be contacted to discuss possible enrollment. Patients with significant ascites defined as European Association for the Study of the Liver \> grade 2, or with asymptomatic pleural effusions with an estimated size \>200 mL, or with symptomatic pleural effusion of any size will be excluded.

Inclusion Criteria

Exclusion Criteria

* 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 (American Society of Clinical Oncology-College of American Pathologists).
* 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 investigator, co-investigator 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
* Alanine aminotransferase or aspartate aminotransferase \<2.5x the ULN
* Alkaline phosphatase \<2.5x the ULN or \<5x the ULN if secondary to liver metastasis
* Able to provide confirmed consent

* Prior allergy or adverse reaction to methotrexate
* New York Heart Association Heart Failure Class \>3 (see Appendix II)
* Active diabetes insipidus
* Active mucositis
* Chemotherapy or stereotactic radiotherapy within the last 2 weeks
* Partial brain radiotherapy (i.e., less than or equal to 40% of total brain volume) within the last two weeks
* Whole brain radiotherapy within the last 6 months or partial brain radiotherapy exceeding greater than 40% of total brain volume in 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
* 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 investigators or co-investigators should be contacted to discuss possible enrollment. Patients with significant ascites defined as European Association for the Study of the Liver \> grade 2, or with asymptomatic pleural effusions with an estimated size \>200 mL, or with symptomatic pleural effusion of any size will be excluded.

Contacts and Locations

Study Contact

Cindy Miller

CONTACT

cytmill@wakehealth.edu

Strowd Roy, MD

CONTACT

rstrowd@wakehealth.edu

Principal Investigator

Roy Strowd, MD

PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Study Locations (Sites)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287

United States

Siteman Cancer Center- Washington University School of Medicine in St. Louis

Saint Louis, Missouri, 63130

United States

Comprehensive Cancer Center at Wake Forest University (CCCWFU)

Winston-Salem, North Carolina, 27157

United States

Collaborators and Investigators

Sponsor: Wake Forest University Health Sciences

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

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2015-05

Study Completion Date2027-01

Study Record Updates

Study Start Date2015-05

Study Completion Date2027-01

Terms related to this study

Additional Relevant MeSH Terms

Metastatic Breast Cancer
Leptomeningeal Disease