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

Официальное название

A Two-Part, Phase 1/2a Trial to Determine the Maximum Tolerated Dose, Safety, and Tolerability of Rhenium (186Re) Obisbemeda (Rhenium-186 NanoLiposome, 186RNL) Delivered Via Convection Enhanced Delivery (CED) in Supratentorial Recurrent, Refractory, or Progressive Pediatric Ependymoma and High-Grade Glioma (HGG)

Обзор

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.

Вмешательства

• Препарат Rhenium-186 Nanoliposome
  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.

Первичные конечные точки

• Maximum Tolerated Dose (MTD) [Срок оценки: 28 days]
• Overall Response Rate (ORR) by RANO in Ependymoma [Срок оценки: 90 days]
• Progression-Free Suvival at 12 months (PFS12) in HGG [Срок оценки: 12 months]

Вторичные конечные точки (6)

• Safety of 186RNL Dose [Срок оценки: 28 days]
• Dose Distribution of 186RNL [Срок оценки: 8 days]
• Neuropsychologic Outcome [Срок оценки: 1 year]
• Progression-Free Survival at 24 Months (PFS24) in Ependymoma [Срок оценки: 24 months]
• Overall Response Rate (ORR) by RANO in HGG [Срок оценки: 90 days]
• Overall Survival at 24 Months (OS24) [Срок оценки: 24 months]

Критерии участия

Критерии включения

• 6 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)

6\) Acceptable renal function:

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• Serum creatinine ≤1.5xULN

7\. Acceptable hematologic status (without hematologic support):

• ANC ≥1000 cells/uL
• Platelet count ≥100,000/uL
• Hemoglobin ≥9.0 g/dL

8\. All subjects of childbearing potential must have a negative serum pregnancy test, and 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\. Life expectancy of at least 2 months.

\*Will consider treatment of subjects up to 25 years of age on a per-patient basis if no other co-morbidities are present that require subspecialty consultation outside of neurosurgical and oncologic care.

Критерии исключения

• 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.
• Standard radiation therapy within 12 weeks prior to study registration.
• Any systemic therapy within 28 days or 2 half-lives, whichever is longer, prior to study registration (this may include investigational agents, small-molecule kinase inhibitors, non-cytotoxic hormonal therapy, biologic agents, metronomic/protracted low-dose chemotherapy, etc.).
• Nitrosoureas or mitomycin C within 42 days prior to study registration.
• Psychiatric illness/social situations that would limit compliance with the study requirements.
• A tumor located within 1.0cm of a ventricle AND it is determined by the surgeon, PI, and Sponsor to be a risk for drug extravasation to the subarachnoid space if given catheter placement and drug administration.
• A tumor within 1.5cm of critical structures, including the optic chiasm, optic nerves, or brainstem.
• Evidence of acute intracranial or intratumoral hemorrhage either by magnetic resonance imaging (MRI) or computerized tomography (CT) scan (subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible).
• Treatment with antiepileptic medications must have a two-week history of a stable dose of antiepileptic without seizures prior to study registration.
• Patients with corticosteroid requirements to control cerebral edema must be maintained at a stable or decreasing dose for a minimum of two weeks without progression of clinical symptoms prior to study registration.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07061626 · CA-2024-PBC-001 · HT9425-24-1-1035

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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