Intraventricular Administration of Rhenium-186 NanoLiposome for Leptomeningeal Metastases

NCT ID: NCT05034497

Last Updated: 2025-03-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-06
• Study Completion Date: 2026-06-30

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).

Detailed Description

This Phase I clinical study evaluates a single dose of 186RNL (radionuclide clinical study drug) administered through an intraventricular catheter (Ommaya reservoir) in participants with Leptomeningeal Metastases (LM).

The clinical study treatment consists of a single administered 5cc dose of 186RNL per participant.

The clinical study will include the evaluation at separate dose levels. Three to six participants may be treated at each dose.

The maximum number of participants to be enrolled in the study is 27.

The clinical study treatment will be administered, following a CSF flow study, on an outpatient basis by the clinical study physician.

Participants will be followed for up to 12 months after the clinical study drug is administered.

The U.S. Food and Drug Administration (FDA) has not approved 186RNL for this specific disease.

Conditions

Leptomeningeal Metastasis

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation

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.

Group Type: EXPERIMENTAL

186RNL

Intervention Type: 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.

Interventions

186RNL

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.

Intervention Type: DRUG

Other Intervention Names

Rhenium-186 NanoLiposome

Eligibility Criteria

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:

a. Current EANO-ESMO Clinical Practice Guidelines Type 1 and 2 LM of any primary type. 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 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.

2. Obstructive or symptomatic communicating hydrocephalus.

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

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. Prior, non-CNS radiation for 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.

1. If the washout period is satisfied, the patient may be enrolled, providing all other I/E criteria are satisfied.

2. 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.

10. 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.

11. 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.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Plus Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew Brenner, PhD

Role: PRINCIPAL_INVESTIGATOR

The Cancer Therapy and Research Center at UTSHSCSA

Locations

Northwestern Memorial Hospital Olson Pavilion

Chicago, Illinois, United States

Northshore University Hospital

Manhasset, New York, United States

Lenox Hill Hospital

New York, New York, United States

Ohio State University Hospital

Columbus, Ohio, United States

Universiy of Texas Southwestern Medical Center

Dallas, Texas, United States

UT Health Science Center San Antonio / Mays Cancer Center

San Antonio, Texas, United States

Countries

United States

Other Identifiers

2021-LM-001

Identifier Type: -

Identifier Source: org_study_id