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Lay Description

This is an open-label, multicenter, Phase 1 dose-escalation study to establish the safety and tolerability of a single dose of 186RNL by the intraventricular route (via intraventricular catheter) and to identify a maximum tolerated dose (MTD) and/or maximum feasible dose (MFD).

Category

  • Cancers and Other Neoplasms
IRB Number
20210718HU
NCT Number
ct.gov registration not required
Open to Enrollment
Yes

Eligibility

Eligible Ages
18 and over
Eligible Genders
All
Accepts Healthy Volunteers

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 written informed consent document approved by the site-specific IRB.

3. Subject has proven and documented LM that meets the requirements for the study:

• EANO-ESMO Clinical Practice Guidelines Type 1 and 2 (with the exception of 2D) LM of any primary type.

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 with normal liver

• AST (SGOT) and ALT (SGPT) ≤ 5.0 times upper limit of normal for subjects with liver 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 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.

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

Exclusion Criteria

1. The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study.

2. Obstructive or symptomatic communicating hydrocephalus

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

4. Females of childbearing potential who are pregnant, breast feeding, or may possibly be pregnant without a negative serum pregnancy test

5. Serious intercurrent illness, such as progressive systemic (extra leptomeningeal) disease, 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

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 or acquired 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.

9. Myelopathy following spinal irradiation greater than 3 weeks prior to the first dose of 186RNL.

10. Systemic chemotherapeutic agents with CNS penetration (such as temozolomide, carmustine, lomustine, capecitabine, carboplatin, vinorelbine, bevacizumab, irinotecan or topotecan) unless they develop or have progressive or persistent leptomeningeal metastases while on these agents.

11. Systemic therapy (including investigational agents and small-molecule kinase inhibitors) within 14 days or 5 half-lives, whichever is shorter, prior first dose of study drug (186RNL).

12. Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug (186RNL).

13. Impaired CSF Flow Study performed on Day -4 to Day -2 based on study imaging and as determined by the investigator.

Study Design

Arm Groups

Study Contact


Regulatory Point of Contact
Frances Crawford
(210) 450-5037
crawfordf1@uthscsa.edu

Regulatory Point of Contact
Sonia Creighton
(210) 450-1366
creighton@uthscsa.edu

Regulatory Point of Contact
Myrna Montenegro
(210) 450-5954
montenegro@uthscsa.edu

Regulatory Point of Contact
Mailbox Ctrc Regulatory Affairs
regaffapp@uthscsa.edu

Regulatory Point of Contact
Kathleen Rodriguez
(210) 450-1365
rodriguezk3@uthscsa.edu

Regulatory Point of Contact
Benjamin Schleif
(210) 450-1366
schleifb@uthscsa.edu

Regulatory Point of Contact
Morgan Seekatz
(210) 450-1133
seekatz@uthscsa.edu

Principal Investigator
Andrew Brenner