Intraventricular Administration of Rhenium-186 NanoLiposome for Leptomeningeal Metastases

Inclusion Criteria:

1. At least 18 years of age at time of screening.

2. Ability to understand the purposes and risks of the study and has signed a writteninformed consent document approved by the site-specific IRB.

3. Subject has proven and documented LM that meets the requirements for the study: a. Current EANO-ESMO Clinical Practice Guidelines Type 1 and 2 LM of any primarytype. 2D is excluded.

4. Karnofsky performance status of 60 to 100.

5. Acceptable liver function:

• Bilirubin 1.5 times upper limit of normal

• AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal for subjects withnormal liver

• AST (SGOT) and ALT (SGPT) ≤ 5.0 times upper limit of normal for subjects withliver metastasis

• Acceptable renal function with serum creatinine ≤ 2 times upper limit of normal

6. Acceptable hematologic status (without hematologic support):

• ANC ≥ 1000 cells µL

• Platelet count ≥ 75,000/µL

• Hemoglobin ≥ 9.0 g/dL

7. All women of childbearing potential must have a negative serum pregnancy test atscreening. Male and female subjects must agree to use effective means ofcontraception (for example, surgical sterilization or the use of barriercontraception with either a condom or diaphragm in conjunction with spermicidal gelor an IUD) with their partner from entry into the study through 6 months after thelast dose.

8. Subjects with a creatinine clearance greater than or equal to 60 mL/min (using theCockcroft-Gault Equation) for males and females.

Exclusion Criteria:

1. The subject has not recovered to National Cancer Institute (NCI) Common TerminologyCriteria for Adverse Events (CTCAE v5.0) Grade ≤ 1 from AEs due to antineoplasticagents, investigational drugs, or other medications that were administered prior tostudy. Prior AEs due to alopecia, anemia, and lymphopenia are not required to berecovered to Grade ≤ 1 prior to 186RNL treatment, assuming other inclusion criteriaare satisfied.

2. Obstructive or symptomatic communicating hydrocephalus.

3. Ventriculo-peritoneal or ventriculo-atrial shunts without programable valves orcontraindications to placement of Ommaya reservoir.

4. Females of childbearing potential who are pregnant, breast feeding, or may possiblybe pregnant without a negative serum pregnancy test (see inclusion criteria).

5. Serious intercurrent illness, such as progressive systemic (extra leptomeningeal)disease, clinically significant cardiac arrhythmias, uncontrolled systemicinfection, symptomatic congestive heart failure or unstable angina pectoris within 3months prior study drug, myocardial infarction, stroke, transient ischemic attackwithin 6 months, seizure disorder with any seizure occurring within 14 days prior toconsenting or encephalopathy.

6. Active severe non hematologic organ toxicity such as renal, cardiac, hepatic,pulmonary, or gastrointestinal systemic toxicity grade 3 or above.

7. Significant coagulation abnormalities such as inherited bleeding diathesis oracquired coagulopathy with unacceptable risks of bleeding.

8. Patients who had any dose to the spinal cord or whole brain radiation therapy,regardless of when the radiation treatment was delivered. Prior, non-CNS radiationfor primary tumor is allowed.

9. Systemic chemotherapeutic agents with CNS penetration (such as temozolomide,carmustine, lomustine, capecitabine, carboplatin, vinorelbine, bevacizumab,irinotecan or topotecan) are excluded if given within 14 days or 5 half-lives,whichever is shorter, prior to 186RNL treatment.

10. If the washout period is satisfied, the patient may be enrolled, providing allother I/E criteria are satisfied.

11. If the patient is undergoing systemic chemotherapy with CNS penetration (suchas temozolomide, carmustine, lomustine, capecitabine, carboplatin, vinorelbine,bevacizumab, irinotecan or topotecan) and they develop or haveprogressive/persistent LM while on the agent, they may be included in the trialat the PI's discretion.

12. Systemic therapy (including investigational agents and small-molecule kinaseinhibitors) is excluded if given within 14 days or 5 half-lives, whichever isshorter, prior to 186RNL treatment. a. If the washout period is satisfied, the patient may be enrolled, providing allother I/E criteria are satisfied.

13. Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dosechemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, areexcluded if given within the above timepoints prior to 186RNL treatment. a. If the washout period is satisfied, the patient may be enrolled, providing allother I/E criteria are satisfied.

14. Impaired CSF Flow Study, within 4 +/- 3 days of 186RNL treatment, based on studyimaging and as determined by the investigator.