RNA Lipid Particles Targeting Pediatric Recurrent Intracranial Malignancies and Other systEmic Solid Tumors

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Recurrent Pulmonary Osteosarcoma, Recurrent High-grade Glioma

In brief

The Investigators have demonstrated in preclinical studies that RNA liposomes activate APCs, induce antigen-specific T cell immunity, and can supplant DCs in a cell therapy model for HGG and have shown feasibility and activity of this approach in preclinical models and in canine patients with a spontaneous malignant glioma. In one arm of this study, we will investigate the safety and immunologic activity of RNA-LP vaccines in pediatric patients with recurrent pHGG. The investigators have also shown that intravenous administration of tumor mRNA loaded lipid particles (LPs) localizes primarily to lung, transfect antigen presenting cells (APCs) and lead to an activated T cell response for induction of anti-tumor immunity. In contrast to other formulations, RNA-LPs recruit multiple arms of the immune system (i.e. innate/adaptive), and remodel the systemic/intratumoral immune milieu, which remain potent barriers for vaccine, cellular, and checkpoint inhibiting immunotherapies. After only a single RNA-LP vaccine, the bulk of systemic and intratumoral dendritic cells (DCs) in mice display an activated phenotype; these activated DCs (harvested from tumors) expand antigen specific T cell immunity. In immunologically resistant pulmonary osteosacroma murine tumor models (i.e. K7M2), RNA-LPs induce robust anti-tumor efficacy in settings where immune checkpoint inhibitors (i.e. anti-PD-L1 therapy) do not confer therapeutic benefit. The investigators have already demonstrated safety of RNA-LPs in acute/chronic murine toxicity studies, and in client-owned canine trial. In this study, we will investigate the manufacturing feasibility, safety and immunologic activity of RNA-LP vaccine in patients with recurrent pulmonary or unresectable osteosarcoma and recurrent pHGG.

Key facts

Study ID: NCT05660408
Run by: University of Florida
People needed: 36
Starts: 2025-03-12
Expected to finish: 2035-10-01
Last updated by the study team: 2026-03-09

Who can join

Age: 3 and older, up to 39. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients with recurrent or progressive pediatric high-grade glioma (pHGG)
Patients must be age 3-25 years
Diagnosis:
Patients must have had a prior histologically-diagnosed pHGG(including but not limited to: Astrocytoma WHO Grade 3 or 4 and Glioblastoma WHO Grade 4 by histopathology or molecular studies, per 2021 WHO Classification of Tumors of the CNS57, WHO CNS5).
Patients with M+ disease without gliomatosis cerebri (see definition under exclusion criteria) ARE eligible.
Recurrent pHGG involving the midline structures other than those intrinsically located within the pons ARE eligible.
Patients with mismatch repair deficient (MMRD) tumors refractory to immune checkpoint inhibitors ARE eligible.
Patients must have recurred or progressed after receiving surgery/biopsy and radiation therapy as frontline standard-of-care treatments in primary disease.
Patients must have MRI evidence of probable recurrent pHGG. Patients must be clinically eligible for standard-of-care surgical resection/biopsy and sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles.
Performance Level Karnofsky ≥ 60% for patients ≥ 16 years of age and Lansky ≥ 60% for patients ≤ 16 years of age
Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Participants with post-surgical neurological deficits should have deficits that are stable for a minimum of 2 week prior to enrollment.
Prior Therapy
Patients must have recovered from all acute toxic effects of all prior anti-cancer therapy (all adverse events must have improved to grade 1 or better):
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: ≥ 21 days after the last dose of myelosuppressive chemotherapy. If questions, the agent and duration can be discussed with the study chair.
Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or ANC counts): ≥ 14 days after the last dose of agent. If questions, the agent and duration can be discussed with the study chair.
Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
Corticosteroids: All systemically administered corticosteroids must be stable or decreasing for ≥ 1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg/m2/day. Corticosteroid physiologic replacement therapy for management of pituitary/adrenal axis insufficiency and/or topical administration (e.g. inhaled or dermatologic) is allowed.
Hematopoietic growth factors: ≥14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
Interleukins, Interferons, and Cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon, or cytokines.
Stem cell infusions (with or without TBI):
Autologous stem cell infusion including boost infusion: ≥ 30 days.
Cellular Therapy: ≥ 42 days after the completion of any type of cellular therapy (e.g., modified T cells, NK cells, dendritic cells, etc.)
XRT/External Beam Irradiation, including Protons: ≥ 90 days after local XRT unless recurrence is a new enhancement on MRI outside the radiation treatment field; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis.
Radiopharmaceutical therapy (e.g., radiolabeled antibody): ≥ 42 days after systematically administered radiopharmaceutical therapy.

Where it is running

UF Health — Gainesville, Florida, United States

Full record on ClinicalTrials.gov

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