Intraventricular Administration of Rhenium-186 NanoLiposome for Leptomeningeal Metastases

NCT05034497 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2021-LM-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open-label Phase I clinical study that will administer a single dose of 186RNL via intraventricular catheter for treatment of Leptomeningeal Metastases (LM).

Conditions

Leptomeningeal Metastasis

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of adverse events (AE) and serious adverse events (SAE)

  Safety will be evaluated by the incidence of AEs and SAEs graded according CTCAE version 5.0.

  12 months

• Incidence of dose-limiting toxicities (DLT)

  Maximum Tolerated Dose (MTD) will be evaluated by testing increasing doses with 3 to 6 participants in each cohort. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants.

  12 months

Secondary Outcomes (4)

• Determination of the overall response rate (ORR)

  12 months

• Determination of the duration of response (DoR)

  12 months

• Determination of progression free survival (PFS)

  12 months

• Overall survival (OS)

  12 Months

Study Arms (1)

Dose Escalation

EXPERIMENTAL

Each participant will receive a single 5cc administration of 186RNL. At each dose level, a minimum of three to a maximum of six participants will be enrolled. If no dose limiting toxicity is observed in the initial three participants, then the next higher dose level cohort will open for enrollment. The dose escalation scheme will follow a modified Fibonacci dose escalation scheme.

Drug: 186RNL

Interventions

186RNL DRUG

All participants will be required to have an Ommaya Reservoir and a CSF Flow Study. Participants will receive a single 5cc dose of 186RNL via Ommaya Reservoir.

Also known as: Rhenium-186 NanoLiposome

Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age at time of 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.
• 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 primary type. 2D is excluded.
• 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
• Acceptable renal function with serum creatinine ≤ 2 times upper limit of normal
• Acceptable hematologic status (without hematologic support):
• ANC ≥ 1000 cells µL
• Platelet count ≥ 75,000/µL
• Hemoglobin ≥ 9.0 g/dL
• 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.

You may not qualify if:

• Obstructive or symptomatic communicating hydrocephalus.
• Ventriculo-peritoneal or ventriculo-atrial shunts without programable valves or contraindications to placement of Ommaya reservoir.
• 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.
• Active severe non hematologic organ toxicity such as renal, cardiac, hepatic, pulmonary, or gastrointestinal systemic toxicity grade 3 or above.
• Significant coagulation abnormalities such as inherited bleeding diathesis or acquired coagulopathy with unacceptable risks of bleeding.
• 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 radiation for primary tumor is allowed.
• 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.
• If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.
• If the patient is undergoing systemic chemotherapy with CNS penetration (such as temozolomide, carmustine, lomustine, capecitabine, carboplatin, vinorelbine, bevacizumab, irinotecan or topotecan) and they develop or have progressive/persistent LM while on the agent, they may be included in the trial at the PI's discretion.
• Systemic therapy (including investigational agents and small-molecule kinase inhibitors) is excluded if given within 14 days or 5 half-lives, whichever is shorter, prior to 186RNL treatment.
• a. If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.
• Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, are excluded if given within the above timepoints prior to 186RNL treatment.
• a. If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.
• Impaired CSF Flow Study, within 4 +/- 3 days of 186RNL treatment, based on study imaging and as determined by the investigator.

Sponsors & Collaborators

• Plus Therapeutics: lead

Study Sites (6)

Northwestern Memorial Hospital Olson Pavilion

Chicago, Illinois, 60611, United States

Location

Northshore University Hospital

Manhasset, New York, 11030, United States

Location

Lenox Hill Hospital

New York, New York, 10075, United States

Location

Ohio State University Hospital

Columbus, Ohio, 43201, United States

Location

Universiy of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

UT Health Science Center San Antonio / Mays Cancer Center

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Meningeal Carcinomatosis

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Study Officials

• Andrew Brenner, PhD

  The Cancer Therapy and Research Center at UTSHSCSA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2021
• First Posted: September 5, 2021
• Study Start: December 6, 2021
• Primary Completion: December 21, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 26, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)