Clinical Trials for Prevention, Early Detection and Treatment of Breast Cancer Leptomeningeal Metastases

This is a study of biomarkers (signs) in the spinal fluid of women with breast cancer metastasized to the leptomeningeal. Spinal fluid samples will be taken during the first lumbar puncture performed on the patient in the clinic, in other words, no additional procedure will be required of study participants. This biomarker study is taking place in France.

This is a phase II study prospective study to evaluate high dose methotrexate in breast cancer with leptomeningeal disease in patients with or without brain metastases. It will be looking to see if high dose methotrexate penetrates the blood brain barrier getting into the spinal fluid and affecting bulky leptomeningeal disease. Patients must be triple negative, HER2-positive, and hormone refractory and can not have had whole-brain radiation in the last 6 months or chemotherapy and stereotactic radiosurgery in the last two weeks.

This is a phase II trial taking place in China, that is looking at the safety and efficacy of combining radiotherapy and intrathecal chemotherapy for leptomeningeal disease. Patients will be randomized to receive either: methotrexate or ARA-C (cytarabine) concurrently.

This is a phase II study of patients with any number of prior treatments. Pembrolizumab (Keytruda) is an immumotherapeutic treatment that has been approved for melanoma and certain types of lung cancer, head and neck cancer, lymphoma, and urothelial cancer. It works by stopping cancer cells from shielding themselves from the immune system. Patients must not have had any prior treatment with PD-1 therapy and developed progressive disease.

The purpose of this study is to see if DNA from cancer tumor cells can be found in cerebral spinal fluid before it is possible to find malignant cancer cells/ Those who enter the trial must have symptoms of leptomeningeal metastases such as headache, vision problems, hearing loss, cognitive loss etc. but can not have had previous central nervous system disease including brain metastases.

This is a phase l study to determine the proper dose and safety of afatinib for women with HER2-positive brain metastases. Afatinib has already been approved for certain types of lung cancer and melanoma. It is an immunotherapeutic drug that keeps cancer cells from shielding themselves from the immune system.  There will be groups in the trial each with an escalating dose of afatinib. To enter this trial one previous treatment for brain metastases must have failed, and at least 28 days must have elapsed after whole brain radiation or radiosurgery.

This is a Phase II non-randomized clinical trial to test the safety and efficacy of abemaciclib in hormone receptor positive metastatic breast cancer that is no longer responding to hormonal treatment. Patients can have either Her2+ or Her2- disease. They must have already completed local therapy brain metastases (whole-brain, stereotactic radiation, or surgical removal of brain metastases) and not require any local therapy immediately.  Abemaciclib is a CDK 4/6 inhibitor which blocks cancer cell growth and replication.

 The purpose of this Phase I study is to find out if capecitabine can be given safely with different doses of lapatinib in patients with HER2-positive breast cancerwith brain metastases. Both drugs have been shown to penetrate the blood-brain barrier and to shrink brain metastases and/or leptomeningeal disease. 

The purpose of this French Phase lll study is to compare the progression free survival of leptomeningeal metastasis with the use of intrathecal delivery of liposomal cytarabine, (a chemotherapy drug) versus treatment of physician’s choice (chemotherapy, hormonal therapy, or targeted therapy) delivered intraveneously (into the veins). Intrathecal delivery of a drug is done by lumber puncture (spinal tap) or through a device placed under the scalp. It infuses the drug directly into the cerebrospinal fluid targeting the cancer cells. Life expectancy must be at least 2 months. Brain metastases are allowed if they are not symptomatic.

This Phase ll study will be looking at whether high-dose methotrexate is effective at controlling leptomeningeal metastasis caused by breast cancer. The methotrexate will be delivered intravenously (into the veins). Patients may also have brain metastases. Everyone in the study receives the treatment.

 In this phase lll trial patients will either receive liposomal cytarabine (chemotherapy) either intravenously (through the veins) or intrathecally (directly into the leptomeninges through a hole in the scalp--See treatment of leptomeningeal disease in this website). Patients can have stable brain metastases but cannot have a mass in the leptomeninges larger than 1 cm. This trial is being done in France.

A French Phase l/ll Trial of Herceptin delivered intrathecally or intraventricularly into the meninges, the fluid surrounding the spinal cord and brain where breast cancer cells can metastasize and form tumors. In intrathecal delivery, the Herceptin is delivered directly into the brain. Intraventricular delivery is directly into the fluid surrounding the spine. For a more detailed description of intrathecal infusion, see the treatments section on  leptomeningeal disease. This trial allows women with untreated asymtomatic brain metastases or stable brain metastases after treatment. This dosing and safety study assigns patients to doses starting at 30 mg weekly and going up to 150mg weekly.  See the bibliography for case studies that have shown that off label use of this experimental treatment can be effective in some cases, although the proper dose has not yet been established.