Determine Maximum Tolerated Dose, Safety, and Tolerability of Rhenium (186Re) in Pediatric Recurrent, Refractory or Progressive Ependymoma and High-Grade Glioma

NCT07061626 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: CA-2024-PBC-001HT9425-24-1-1035
• Study Type: interventional
• Target: 56
• Locations: 0 countries
• Sites: N/A

Brief Summary

Pediatric patients 6-21 years of age with supratentorial recurrent, refractory, or progressive pediatric ependymoma and high-grade glioma (HGG) will be included in this study of treatment with Rhenium-186 Nanoliposome (186RNL). Phase 1 of the study will look to determine the maximum tolerated dose (MTD) of 186RNL in this patient population. Phase 2 of the study will use the recommended dose determined in Phase 1 to continue to look at overall response rate and progression-free survival following 186RNL treatment.

Conditions

Ependymoma; High Grade Gliomas

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD)

  Determine the maximum tolerated dose (MTD) of 186RNL administered by convection-enhanced delivery (CED) in subjects with supratentorial recurrent, refractory, or progressive pediatric ependymoma or HGG.

  28 days

• Overall Response Rate (ORR) by RANO in Ependymoma

  Determine the best overall response rate (ORR) by Radiographic Assessment in Neuro-Oncology (RANO) criteria following 186RNL administration in subjects with supratentorial recurrent, refractory, or progressive pediatric ependymoma.

  90 days

• Progression-Free Suvival at 12 months (PFS12) in HGG

  Determine progression-free survival at 12 months (PFS12) in subjects with supratentorial recurrent, refractory, or progressive pediatric HGG.

  12 months

Secondary Outcomes (6)

• Safety of 186RNL Dose

  28 days

• Dose Distribution of 186RNL

  8 days

• Neuropsychologic Outcome

  1 year

• Progression-Free Survival at 24 Months (PFS24) in Ependymoma

  24 months

• Overall Response Rate (ORR) by RANO in HGG

  90 days

Other Outcomes (2)

• Overall Response Rate (ORR) by RAPNO

  90 days

• Tissue Sample from Standard of Care Surgical Resection of Tumor

  28 days

Study Arms (4)

Phase 1a - Cohort A

EXPERIMENTAL

Up to six subjects will be enrolled in Cohort A. Tumor size will be limited to a maximum diameter of (less than or equal to) ≤2 cm and a maximum volume of (less than or equal to) ≤4.2 mL. Up to two CED catheters will be utilized in Cohort A at the discretion and consensus of the PI, neurosurgeon, and/or study team. The concentration of 186RNL infusate in Cohort A is 0.5 mCi/mL, with a corresponding estimated absorbed dose of \~87.5Gy.

Drug: Rhenium-186 Nanoliposome

Phase 1a - Cohort B

EXPERIMENTAL

Up to six subjects will be enrolled in Cohort B. Tumor size will be limited to a maximum diameter of 3.5 cm in the longest axis and a maximum volume of 22.4 mL. Up to 5 total catheters may be used for Cohort B at the discretion and consensus of the PI, neurosurgeon, and/or study team to ensure total tumor volume coverage. The concentration of 186RNL infusate in Cohort B is 1.0 mCi/mL with a corresponding estimated absorbed dose of \~176Gy (\~2x Cohort A).

Drug: Rhenium-186 Nanoliposome

Phase 1b

EXPERIMENTAL

Phase 1b continued dosing escalation will be defined following review of the safety data from Phase 1a.

Drug: Rhenium-186 Nanoliposome

Phase 2

EXPERIMENTAL

The Phase 2 expansion study will utilize the maximum tolerable dose (MFD) determined from the Phase 1 dose escalation study. If no maximal tolerable dose is found, tumors may be treated up to an estimated total absorbed dose of 176 Gy. Varying concentrations of 186RNL infusate (0.5-2.5 mCi/mL) may be used to achieve this maximum tolerable dose while maintaining total tumor volume coverage. Phase 2a will enroll an additional 12 patients with a diagnosis of recurrent, refractory, or progressive ependymoma and an additional 20 patients with a diagnosis of recurrent, refractory, or progressive HGG.

Drug: Rhenium-186 Nanoliposome

Interventions

Rhenium-186 Nanoliposome DRUG

Rhenium (186Re) Obisbemeda (Rhenium-186 NanoLiposome, 186RNL), BMEDA-chelated-186rhenium encapsulated within liposomes, allows the 186Re to be directly delivered to the site of the tumor through CED and maintain localization at the site of infusion.

Phase 1a - Cohort A; Phase 1a - Cohort B; Phase 1b; Phase 2

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• years to 21 years\* of age.
• Lesion number and size:
• Phase 1a/b only: A single lesion (less than or equal to) ≤3.5 cm (longest axis) and volume of (less than or equal to) ≤22.4 mL as the largest tumor (subsequent to individual Cohort lesion size requirements).
• Phase 2a only: A single lesion or any number of multiple lesions separated by (less than or equal to) ≤3 cm; each lesion (less than or equal to) ≤3.5 cm (longest axis) and volume of (less than or equal to) ≤22.4 mL as the largest tumor.
• Diagnosis:
• a) Documented recurrent, refractory, or progressive ependymoma or HGG not eligible for resection or no longer receiving standard of care.
• i) Phase 2a only: May include patients with recurrent, refractory, or progressive ependymoma or HGG where SOC surgery could be safely delayed four (4) weeks post-infusate.
• b) Documented histologically confirmed high-grade glioma \[following 2021 WHO CNS5 glioma nomenclature, e.g., Anaplastic astrocytoma, Anaplastic pleomorphic xanthoastrocytoma (PXA), Anaplastic ganglioglioma, Anaplastic oligodendroglioma, Glioblastoma, Diffuse midline glioma, H3K27M mutant\].
• Karnofsky Performance Status ≥ 60. For subjects \<16 years of age, Lansky score ≥ 60.
• Acceptable liver function:
• Bilirubin ≤ 1.5 times the upper limit of normal
• AST (SGOT) and ALT (SGPT) ≤ 3.0 times the upper limit of normal (ULN)
• \) Acceptable renal function:
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• Serum creatinine ≤1.5xULN

You may not qualify if:

• Spinal disease.
• Infratentorial location of tumor.
• Involvement of the leptomeninges.
• Serious intercurrent illness, as determined by the treating physician, which would compromise either patient safety or study outcomes such as:
• Hypertension (two or more blood pressure readings performed at screening of systolic blood pressure (SBP) or diastolic blood pressure (DBP) above 95th percentile for age) despite optimal treatment.
• Active medically significant infection unresponsive to antibiotics (e.g., non-healing wound, ulcer), uncontrolled systemic infection, or bone fracture.
• Clinically significant cardiac arrhythmias.
• Untreated hypothyroidism.
• Congestive heart failure.
• Myocarditis.
• Inherited bleeding diathesis or coagulopathy with the risk of bleeding.
• Known active malignancy other than ependymoma or high-grade glioma.
• Any of the following prior anticancer therapy:
• Prior treatment with Bevacizumab or other VEGF agents within 12 months prior to study registration.
• Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy, or intra-operative radiotherapy (IORT) to the target site at any time prior to study registration.

Sponsors & Collaborators

• Plus Therapeutics: lead
• Ann & Robert H Lurie Children's Hospital of Chicago: collaborator

MeSH Terms

Conditions

Ependymoma

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

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

Study Record Dates

• First Submitted: May 3, 2025
• First Posted: July 11, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: July 11, 2025

Record last verified: 2025-07