Multiple Dose Intraventricular Administration of Rhenium-186 NanoLiposome for Leptomeningeal Metastases

Eligibility Criteria

• 1. At least 18 years of age.
• 2. Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB.
• 3. Documented LM from any primary solid tumor cancer per EANO-ESMO Clinical Practice Guidelines (Types I or IIA-C).
• 4. Karnofsky performance status of 70 to 100.
• 5. Acceptable liver function:
• 1. Bilirubin ≤ 1.5 times the upper limit of normal.
• 2. AST (SGOT) and ALT (SGPT) ≤ 3.0 times the upper limit of normal for subjects with normal liver.
• 3. AST (SGOT) and ALT (SGPT) ≤ 5.0 times the upper limit of normal for subjects with liver metastasis.
• 6. Acceptable renal function:
• 7. Acceptable hematologic functioning (without hematologic support):
• 1. ANC ≥ 1000 cells μL.
• 2. Platelet count ≥ 75,000/μL.
• 3. Hemoglobin ≥ 9.0 g/dL.
• 8. All women of childbearing potential must have a negative serum pregnancy test at screening. Male and female subjects must agree to use effective means of contraception (for example, surgical sterilization or the use of barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.
• 9. Normal CSF flow and distribution by an accepted CSF flow study (e.g., 111Indium-DTPA or acceptable substitute) before first treatment with the study drug, based on study imaging interpretation and clinical correlation.
• 10. Corticosteroids are permitted as clinically indicated.
• 1. The subject has not recovered to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade ≤1 from adverse events (AEs) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study, at time of study registration.
• 2. Contraindications to the placement of an intraventricular catheter (i.e., Ommaya reservoir.)
• 3. Presence of or need for a Ventriculo-peritoneal or ventriculo-atrial shunt.
• 4. Females of childbearing potential who are pregnant, breastfeeding, or may possibly be pregnant, without a negative serum pregnancy test (see inclusion criteria).
• 5. Serious intercurrent illnesses, which could interfere with the planned treatment schedule.
• 6. Patients who had any therapeutic radiation dose to the whole brain regardless of when the radiation treatment was delivered, except:
• 1. Prior radiation dose to the spinal cord and/or cauda equina is allowed if the equivalent dose in 2 Gy fractions (EQD2) was ≤ 30 Gy to the spinal cord and/or cauda equina using α/β ratio of 3 and if prior radiotherapy has been \> 14 days and ≤ 6 months, or was ≤45 Gy to the spinal cord and/or cauda equina using α/β ratio of 3 and if prior radiotherapy has been \> 6 months.
• 2. Prior stereotactic radiosurgery (SRS) to the brain or partial brain radiotherapy is allowed if the equivalent dose in 2 Gy fractions (EQD2) was ≤ 30 Gy to brainstem and/or optic structures (optic nerves, optic chiasm) using α/β ratio of 3 and if prior radiotherapy has been \> 14 days and ≤ 6 months, or was ≤ 45 Gy to the brainstem and/or optic structures (optic nerves, optic chiasm) using α/β ratio of 3 and if prior radiotherapy has been \> 6 months.
• 7. Prior or concurrent therapy:
• 8. Projected survival of less than 60 days.