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

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.

This is a Phase 1b/2a study of the combination of two drugs KD019 (tesevatinib) and trastuzumab (Herceptin) for women with Her2-positive leptomeningeal disease. It is a multi-arm trial with only one arm enrolling women with leptomeningeal disease. To enroll women must have a biopsy for pathological confirmation of leptomeningeal disease. They may also have brain metastases which do not need to have progressed after radiation. Tesevatinib blocks a number of breast cancer target genes including HER2, VEGF, EGFR, and SRC and it has been shown in models to cross the blood-brain barrier in very high concentrations.

 The purpose of this study is to learn wither the DNA from cancer tumor cells can be found in fluid that surrounds the brain and spinal cord of patients before malignant cells can be found. The researchers hope this information can be used for the earlier diagnosis of leptomeningeal disease. To be included in the trial, patients must have a previously diagnosed solid tumor (outside of the central nervous system) and have signs or symptoms of leptomeningeal disease such as headache, visual problems, hearing loss, cognitive dysfunction, weakness, numbness, cranial neuropathy, bowel or bladder dysfunction, etc. Patients with prior treatment of central nervous system metastases including brain metastases and other CNS metastases are excluded.

This study will investigate the safety, tolerability, and effectiveness of changing the order of receiving radiation therapy for treating brain cancer and brain metastases. Normal procedure is to follow surgical removal of a brain metastases with stereotactic radiosurgery. This trial reverses the order in the hope that doing the radiation first will lower the risk of cancer spreading throughout the spinal fluid which covers the brain and spinal cord causing leptomeningeal metastases. In addition, patients with smaller brain metastases will start at a lower dose of radiation than those with larger brain metastases. To qualify for the trial, patients must have brain metastases that can be removed by surgery. The metastases must be between 2 and 6 cm in size and no more than four in number. 

 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.

 This is a phase II study looking at how effective this experimental agent is in treating leptomeningeal disease caused by breast cancer. 2B3-101 is a form of adriamycin made to penetrate the blood-brain barrier. To be in the trial you can't have had your maximum allowable dose of adriamycin. You can have brain metastases. This trial is taking place in the Netherlands.

A Phase I/II trial in the U.S. for women with Her2 positive breast cancer metastasized to the meninges--the fluid that surrounds the spinal chord and brain where breast cancer cells can metastasize and form tumors. Herceptin is delivered directly into the meninges either intrathecally into the brain or by lumbar puncture into the fluid surrounding the spinal cord. For a description of intrathecal infusion, see the treatments section on leptomeningeal disease. The Herceptin is delivered in combination with whole brain radiation therapy. This is a dosing and safety study. Increasing doses will be assigned at 10, 20, 30, and 40mg. Each dosing group will start at loading dose of a twice weekly dose for a 4 week period which is reduced to a once a week dose for 4 weeks and then a dose every 2 weeks for 4 more weeks. See the bibliography for case studies for cases where off-label use of this experimental treatment has been effective, although the proper dose has not yet been established.

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.