Trastuzumab in Treating Leptomeningeal Metastases in Patients with HER2-Positive Cancer

Inclusion Criteria

• Confirmation of HER2 positivity: * Phase I only: Patients with leptomeningeal disease from ependymomas, gliomas, and medulloblastoma will be eligible for phase I but are not required to have HER2 analysis; HER2 testing is only required for breast cancer patients with leptomeningeal metastases; HER2 positive (immunohistochemistry [IHC] 3+ and/or fluorescent in situ hybridization [FISH] positive; IHC 2+ HER2 patients are eligible with reflex FISH positive testing with the ratio >= 2.0) breast cancer patients with leptomeningeal metastases by magnetic resonance imaging (MRI) or CSF (if MRI is negative) are eligible * Phase II only: ALL patients with HER2+ cancers of other histology will be allowed to enroll in phase II if they have leptomeningeal disease; patients may be IHC 3+ and/or FISH positive; IHC 2+ HER2 patients are eligible with reflex FISH positive testing with the ratio >= 2.0 * NOTE: review will be performed for cases not reviewed at the participation institution for confirmation, but will not preclude patients from entering the trial (pathology report showing HER2 positivity is sufficient for registration)
• Patients can have concomitant brain metastases as long as they do not require active treatment or have been treated
• Phase I/II: CSF sampling required to document LM if not documented by MRI; NOTE: patients are still eligible if CSF is negative but LM disease is documented on MRI
• Life expectancy >= 8 weeks
• Creatinine < 1.5 x upper limit of normal (or ULN)
• Bilirubin =< 1.5 x ULN
• Transaminases =< 3.0 x ULN, except in known hepatic disease, wherein may be =< 5 x ULN
• White blood cells (WBC) >= 2.5
• Neutrophils >= 1500
• Platelets >= 75,000
• Hemoglobin >= 9
• Left ventricular ejection fraction (LVEF) > 45%
• Karnofsky performance status (KPS) >= 50
• Patients should be > 24 hours from radiation therapy (RT) treatment to areas of the neuro-axis and all effects of treatment should have resolved
• Patients with a recent surgery should have recovered from all effects of the surgery and be cleared by their surgeon
• There is no limit on prior systemic or IT therapies
• Must be willing to have an Ommaya reservoir placed and a candidate for an Ommaya reservoir placement
• Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study
• Ability to sign an informed consent; can be signed by family member or health care proxy; informed consent must be done prior to registration on study
• All patients must have given signed, informed consent prior to registration on study

Exclusion Criteria

• Cannot be on systemic agents (chemotherapy) that have central nervous system (CNS) penetration (temozolomide, carmustine [BCNU], lomustine [CCNU], etoposide, Xeloda, carboplatin, Navelbine, bevacizumab, CPT-11 and topotecan; note: please check with study principal investigator [PI] [Dr. Raizer] to clarify other agents not listed) unless they develop or have progressive or persistent leptomeningeal metastases while on these agent(s) and have controlled systemic disease * NOTE: may continue on intravenous (IV) trastuzumab, pertuzumab, TDM-1, lapatinib or hormonal agents if controlling systemic disease and developed LM while on therapy * NOTE: patients requiring systemic agents (such as those listed above) are eligible but will not be able to start treatment until after the first assessment by imaging and cytology
• Concurrent external beam radiation is not allowed with the exception of palliative radiotherapy to a localized region for pain control (i.e. vertebral disease, pelvis, etc) which IS allowed while on the study protocol * NOTE: patients may need a CSF flow study at the discretion of the treating principal investigator; if a spinal block is seen by CSF flow study or MRI, it will need local RT prior to treatment
• Patients who have controlled or responding leptomeningeal disease and develop brain metastases can remain on trial if their disease can be controlled with radiosurgery and does not require whole body radiation therapy (WBRT); NO history of any other concomitant cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless in complete remission and off all therapy for the disease for a minimum of 3 years
• Patients should have NO significant medical or psychiatric illness that would interfere with compliance and ability to tolerate treatment as outlined in the protocol
• Women may not be pregnant or breast-feeding
• No known hypersensitivity to trastuzumab