Multiple intraventricular doses of rhenium‑186 nanoliposome for leptomeningeal metastases

A Multicenter Phase 1 Study to Determine the Safety and Efficacy of Multiple Doses at Defined Intervals of Rhenium (186Re) Obisbemeda (Rhenium-186 NanoLiposome, 186RNL) Administered Via Intraventricular Catheter for Any Primary Solid Tumor Cancer With Leptomeningeal Metastases

This trial will test whether giving multiple intraventricular doses of a rhenium‑186 nanoliposome is safe and could help adults with leptomeningeal metastases from solid tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Plus Therapeutics (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 1 site (San Antonio, Texas)
• Trial ID: NCT07098806 on ClinicalTrials.gov

What this trial studies

This open‑label, multicenter Phase 1 trial gives multiple doses of rhenium‑186 nanoliposome (186RNL) through an intraventricular catheter to adults with leptomeningeal metastases from any primary solid tumor. Doses are administered at defined intervals to identify a maximum tolerated dose/maximum feasible dose and an optimal dosing schedule. Primary endpoints focus on safety and tolerability with secondary assessments of preliminary antitumor activity and distribution of the radiotherapeutic. Eligible patients must have adequate performance status and organ function and be able to undergo intraventricular catheter placement.

Who should consider this trial

Good fit: Adults (≥18 years) with confirmed leptomeningeal metastases from a solid tumor who have Karnofsky performance status 70–100 and adequate liver, kidney, and blood counts are ideal candidates.

Not a fit: Patients with poor performance status, inadequate organ or blood counts, or those unable to undergo intraventricular catheter placement are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could provide a new localized treatment option that slows or controls leptomeningeal tumor growth with limited systemic toxicity.

How similar studies have performed: Early clinical work has tested intracranial delivery of radiolabeled liposomes in CNS tumors, but multiple intraventricular dosing of 186RNL for leptomeningeal disease is a relatively novel application.

Eligibility criteria

Inclusion Criteria:

1. At least 18 years of age.
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. Documented LM from any primary solid tumor cancer per EANO-ESMO Clinical Practice Guidelines (Types I or IIA-C).
4. Karnofsky performance status of 70 to 100.
5. Acceptable liver function:

   1. Bilirubin ≤ 1.5 times the upper limit of normal.
   2. AST (SGOT) and ALT (SGPT) ≤ 3.0 times the upper limit of normal for subjects with normal liver.
   3. AST (SGOT) and ALT (SGPT) ≤ 5.0 times the upper limit of normal for subjects with liver metastasis.
6. Acceptable renal function:

   a. Creatinine clearance greater than or equal to 60 mL/min (using the Cockcroft-Gault Equation).
7. Acceptable hematologic functioning (without hematologic support):

   1. ANC ≥ 1000 cells μL.
   2. Platelet count ≥ 75,000/μL.
   3. Hemoglobin ≥ 9.0 g/dL.
8. 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.
9. Normal CSF flow and distribution by an accepted CSF flow study (e.g., 111Indium-DTPA or acceptable substitute) before first treatment with the study drug, based on study imaging interpretation and clinical correlation.
10. Corticosteroids are permitted as clinically indicated.

Exclusion Criteria:

1. The subject has not recovered to the current National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v5.0) Grade ≤1 from adverse events (AEs) due to antineoplastic agents, investigational drugs, or other medications that were administered prior to study, at time of study registration.

   a. Prior AEs due to alopecia, anemia, neutropenia, and lymphopenia are not required to be recovered to Grade ≤1 prior to study registration, assuming other inclusion criteria are satisfied.
2. Contraindications to the placement of an intraventricular catheter (i.e., Ommaya reservoir.)
3. Presence of or need for a Ventriculo-peritoneal or ventriculo-atrial shunt.
4. Females of childbearing potential who are pregnant, breastfeeding, or may possibly be pregnant, without a negative serum pregnancy test (see inclusion criteria).
5. Serious intercurrent illnesses, which could interfere with the planned treatment schedule.
6. Patients who had any therapeutic radiation dose to the whole brain regardless of when the radiation treatment was delivered, except:

   1. Prior radiation dose to the spinal cord and/or cauda equina is allowed if the equivalent dose in 2 Gy fractions (EQD2) was ≤ 30 Gy to the spinal cord and/or cauda equina using α/β ratio of 3 and if prior radiotherapy has been \> 14 days and ≤ 6 months, or was ≤45 Gy to the spinal cord and/or cauda equina using α/β ratio of 3 and if prior radiotherapy has been \> 6 months.
   2. Prior stereotactic radiosurgery (SRS) to the brain or partial brain radiotherapy is allowed if the equivalent dose in 2 Gy fractions (EQD2) was ≤ 30 Gy to brainstem and/or optic structures (optic nerves, optic chiasm) using α/β ratio of 3 and if prior radiotherapy has been \> 14 days and ≤ 6 months, or was ≤ 45 Gy to the brainstem and/or optic structures (optic nerves, optic chiasm) using α/β ratio of 3 and if prior radiotherapy has been \> 6 months.
7. Prior or concurrent therapy:

   a. Intrathecally delivered therapy: i. Concurrent: Concurrent intrathecal therapy. ii. Prior: Intrathecal therapy given less than 14 days before study registration.

   b. Systemically delivered therapy: i. Concurrent: Systemically delivered therapy UNLESS LM develops while on systemically delivered therapy AND the systemically delivered therapy is NOT associated with more than grade 1 myelosuppression.

   ii. Prior: Systemically delivered therapy given less than 28 days before study registration.
8. Projected survival of less than 60 days.

Where this trial is running

San Antonio, Texas

• The Cancer Therapy and Research Center at UTHSCSA — San Antonio, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Rachael Hershey

Conditions Leptomeningeal Metastasis; Neoplastic Processes Neoplasms; Neoplasms; Pathologic Processes; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site