RNA Lipid Particles for Brain Tumor

(RNA PRIME Trial)

Overseen By Marcia Hodik

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Florida

Must be taking: Antiepileptics

Disqualifiers: Diffuse intrinsic pontine glioma, Pregnancy, Immunosuppressive disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 16

36 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

John Ligon, MD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for children and young adults aged 3-25 with recurrent pediatric high-grade gliomas (pHGG) or unresectable osteosarcoma. Participants must have MRI evidence of pHGG, a performance score ≥60%, and be eligible for standard surgical resection/biopsy. Those with stable post-surgical neurological deficits are included, but individuals with certain genetic tumor conditions refractory to other treatments are excluded.

Inclusion Criteria

My child has a recurring or worsening high-grade brain tumor.

I am between 3 and 25 years old.

My MRI shows signs of a likely return of my high-grade glioma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

A single neoadjuvant pp65 RNA-LP (DP1) is administered prior to surgical resection/biopsy

1-2 weeks

1 visit (in-person)

Adjuvant Treatment

Two adjuvant DP1 vaccines are administered every 2 weeks, followed by DP2 vaccinations every 2 weeks for the first 3 doses, then monthly for 9 cycles

12 months

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

14 months

Treatment Details

Interventions

• RNA-LP vaccine

Trial Overview The study tests RNA lipid particle (RNA-LP) vaccines designed to activate immune responses against tumors in the brain and lungs. It explores the safety and immune system activity of these vaccines in patients who've had recurring cancer despite previous treatments. The trial includes two different RNA-LP formulations administered alongside potential surgical interventions.

Participant Groups

Group I: Recurrent pHGG, Arm 2 Experimental Treatment 3 Interventions

pHGG Arm 2-Standard of care surgical resection/biopsy will occur first and all three pp65 RNA-LP (DP1) will be administered in the adjuvant setting. During production of DP2, treatment will begin with DP1 every 2 weeks, beginning a minimum of 7-14 days after surgery/biopsy. DP1 vaccines may continue until production of DP2 is complete (expected 5-8 weeks following initial surgery/biopsy). pp65/tumor mRNA RNA-LP (DP2) vaccinations will begin 7-14 days after the last dose of pp65 RNA-LP (DP1). DP2 treatment will occur approximately every 2 weeks for the first 3 doses. Following the first 3 doses of DP2, patients will receive 9 cycles of monthly DP2 for a total of 12 DP2 vaccines (minimum of 15 overall vaccines).

Group II: Recurrent pHGG, Arm 1 Experimental Treatment 3 Interventions

pHGG Arm 1-A single dose of pp65 RNA-LP (DP1) will be administered prior to standard of care surgical resection/biopsy, followed by at least two adjuvant DP1. During production of pp65/tumor mRNA RNA-LP (DP2) vaccines, treatment with DP1 will continue every 2 weeks. DP1 vaccines may continue until production of DP2 is complete (expected 5-8 weeks following initial surgery/biopsy). pp65/tumor mRNA RNA-LP (DP2) vaccinations will begin 7-14 days after the last dose of pp65 RNA-LP (DP1). DP2 treatment will occur approximately every 2 weeks for the first 3 doses. Following the first 3 doses of DP2, patients will receive 9 cycles of monthly DP2 for a total of 12 DP2 vaccines (minimum of 15 overall vaccines).

Group III: Arm 3-Patients with unresectable OSA in any location Experimental Treatment 3 Interventions

Arm 3-Patients with unresectable OSA in any location. Participants will undergo surgical biopsy for sterile collection of tumor material to make pp65/tumor mRNA RNA-LP (DP2). For adult subjects only in Arm 3, optional biopsy will be repeated within 7 days following DP2 Vaccine #3 administration once hematologic recovery to eligibility criteria, unless medically contraindicated. During production of DP) vaccines, participants will begin treatment with off-the-shelf pp65 RNA-LP (DP1) vaccines every 2 weeks, beginning a minimum of 7 days after initial surgery/biopsy. A minimum of 3 DP1 vaccines will be administered and may continue until production of DP2 is complete (expected 5-8 weeks following initial surgery/biopsy). DP2 vaccinations will begin 7-14 days after the last dose of DP1. DP2 treatment will occur approximately every 2 weeks for the first 3 doses. Participants will receive 9 cycles of monthly DP2 for a total of 12 DP2 vaccines (minimum of 15 overall vaccines).

Group IV: Arm 2-Patients with bilateral pulmonary-only metastatic recurrent OSA Experimental Treatment 3 Interventions

OSA Arm 2-Patients with bilateral pulmonary-only metastatic recurrent OSA Participants will undergo surgical resection for sterile collection of tumor material to make pp65/tumor mRNA RNA-LP (DP2). For subjects in Arm 2, surgery will be again performed on contralateral lung nodules within 7 days following DP1 Vaccine #3. During production of pp65/tumor mRNA RNA-LP (DP2) vaccines, participants will begin treatment with off-the-shelf pp65 RNA-LP (DP1) vaccines every 2 weeks. A minimum of 3 DP1 vaccines will be administered and may continue until production of DP2 is complete (expected 5-8 weeks following initial surgery/biopsy). DP2 vaccinations will begin 14 days after 2nd surgical pulmonary metastectomy. DP2 treatment will occur approximately every 2 weeks for the first 3 doses. Participants will receive 9 cycles of monthly DP2 for a total of 12 DP2 vaccines (minimum of 15 overall vaccines).

Group V: Arm 1-Patients with unilateral pulmonary-only metastatic recurrent OSA Experimental Treatment 3 Interventions

OSA Arm 1-Patients with unilateral pulmonary-only metastatic recurrent OSA Participants will undergo surgical resection for sterile collection of tumor material to make pp65/tumor mRNA RNA-LP (DP2). During production of DP2 vaccines, participants will begin treatment with off-the-shelf pp65 RNA-LP (DP1) vaccines every 2 weeks. A minimum of 3 DP1 vaccines will be administered and may continue until production of DP2 is complete (expected 5-8 weeks following initial surgery/biopsy). DP2 vaccinations will begin 7-14 days after the last dose of DP1. DP2 treatment will occur approximately every 2 weeks for the first 3 doses. Participants will receive 9 cycles of monthly DP2 for a total of 12 DP2 vaccines (minimum of 15 overall vaccines).

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Pediatric Cancer Foundation

Collaborator

Trials

8

Recruited

300+

Alex's Lemonade Stand Foundation

Industry Sponsor

Trials

9

Recruited

1,500+

The Osteosarcoma Institute

Collaborator

Trials

1

Recruited

40+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

The V Foundation for Cancer Research

Collaborator

Trials

21

Recruited

1,300+