Phase 1 Study of WBRT or PCSI With REYOBIQ for Leptomeningeal Metastases

Inclusion Criteria:

* At least 18 years of age at screening
* Ability to understand the purposes and risks of the study and has signed a written informed consent document approved by the site-specific IRB
* Proven and documented LM evidenced by positive CSF cytology or CSF circulating tumor cells, from any primary solid tumor
* Patients may have received prior chemotherapy regimens and prior radiation (there is no limit)
* Karnofsky performance status of 60 to 100
* 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 with normal liver
  * AST (SGOT) and ALT (SGPT) ≤ 5.0 times upper limit of normal for subjects with liver metastasis
* Subjects with a creatinine clearance greater than or equal to 60 mL/min (using the Cockcroft-Gault Equation) for males and females.
* Acceptable hematologic status (without hematologic support):

  * ANC ≥ 1000 cells μL
  * Platelet count ≥ 75,000/μL
  * Hemoglobin ≥ 9.0 g/dL
  * PT/INR and PTT ≤1.5 x ULN, unless treated with anticoagulants
* 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.

Exclusion Criteria:

* The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v6.0) Grade ≤ 1 from AEs due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study. Prior AEs due to alopecia, anemia, and lymphopenia are not required to be recovered to Grade ≤ 1 prior to 186RNL treatment, assuming other inclusion criteria are satisfied.
* Ventriculo-peritoneal or ventriculo-atrial shunts or contraindications to placement of Ommaya reservoir.
* Females of childbearing potential who are pregnant, breast feeding, or may possibly be pregnant without a negative serum pregnancy test (see inclusion criteria).
* Serious intercurrent illness, clinically significant cardiac arrhythmias, uncontrolled systemic infection, symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug, myocardial infarction, stroke, transient ischemic attack within 6 months, seizure disorder with any seizure occurring within 14 days prior to consenting or encephalopathy.
* Active severe non hematologic organ dysfunction such as renal, cardiac, hepatic, pulmonary, or gastrointestinal grade 3 or above.
* Toxicity from prior treatments (grade 3 or above) that have not subsided to grade 1.
* Patients with prior CNS directed EBRT.
* Cytotoxic systemic therapy is excluded if given within 14 days or 5 half-lives, whichever is shorter, prior to 186RNL treatment. Small-molecule kinase inhibitors, targeted therapies, immunotherapy, and hormonal therapy can be given up to the day of treatment per investigator discretion.
* Projected survival of less than 60 days.