RNA Lipid Particles for Brain Tumor

(RNA PRIME Trial)

Overseen By Jessica Crimella, BSN, RN, CCRP

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new RNA-LP vaccine for treating certain aggressive brain tumors and osteosarcoma, a type of bone cancer. Researchers aim to determine if the vaccine can enhance the immune system's ability to fight these cancers. Different study groups focus on brain tumors and various forms of osteosarcoma to assess the vaccine's effectiveness in each case. Individuals with recurrent high-grade brain tumors or osteosarcoma that has spread to the lungs or cannot be surgically removed might be suitable candidates for this trial. As a Phase 1 and Phase 2 trial, it seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you must be willing to take an antiepileptic medication like levetiracetam during the study. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that RNA-lipid particle (RNA-LP) vaccines are promising in terms of safety. In studies with mice and dogs, these vaccines did not cause harmful side effects, even with repeated administration, indicating they are well-tolerated in animals.

In early human studies involving individuals with glioblastoma, a type of brain tumor, RNA-LP vaccines also proved to be safe, with no serious side effects reported. These vaccines aim to help the body's immune system fight tumors by activating certain cells that attack cancer.

As these studies are in the early stages, the main focus remains on ensuring the treatment's safety. Researchers are closely monitoring for any side effects or reactions. So far, the results are encouraging, suggesting that RNA-LP vaccines could be a safe option for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for brain tumors, which often involve chemotherapy and radiation, the RNA-LP vaccine uses a cutting-edge approach by leveraging RNA lipid particles to provoke an immune response against the tumor. This method introduces specific RNA sequences encased in lipid particles to teach the immune system to recognize and attack cancer cells. Researchers are excited about this treatment because it targets tumors more precisely, potentially reducing side effects compared to traditional therapies. Moreover, the personalized nature of the RNA-LP vaccine allows it to be tailored to an individual's specific tumor profile, which could improve its effectiveness and lead to better outcomes for patients with recurrent tumors.

What evidence suggests that this trial's RNA-LP vaccine could be effective for brain tumors and osteosarcoma?

This trial will evaluate RNA-lipid particle (RNA-LP) vaccines for their potential to fight certain cancers by boosting the immune system. Participants will receive RNA-LP vaccines targeting specific proteins, such as pp65, often found in brain tumors like glioblastoma. Research has shown that these vaccines activate special cells that initiate the body's immune response. In animal tests, RNA-LPs successfully shrank tumors and increased immune activity, especially when other treatments failed. In dog trials for bone cancer, RNA-LPs were safe and showed signs of activating the immune system. Overall, early research suggests that RNA-LP vaccines could strengthen the body's natural defenses, making them a strong tool in cancer treatment. ^{2 3 6 7 8}

Who Is on the Research Team?

John Ligon, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04573140

NCT04573140 | A Study of RNA-lipid Particle (RNA-LP) ... This is a first in human Phase I study of RNA-LP vaccines for newly diagnosed adult MGMT unmethylated (low level or undetected) glioblastoma (GBM) and pediatric ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04573140?cond=%22Brain%20Cancer%22&intr=%22vaccines%22&viewType=Table&rank=6

A Study of RNA-lipid Particle (RNA-LP) Vaccines for Newly ... A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11453023/

Personalized mRNA vaccines in glioblastoma therapy A notable example is a Phase I clinical trial (NCT06389591) investigating RNA-lipid particle (RNA-LP) vaccines for recurrent adult GBM, which aims to assess the ...

4. trials.braintumor.org trials.braintumor.org/trials/NCT06389591

RNA-Lipid Particle (RNA-LP) Vaccines for Recurrent Adult ... This is a Phase I study to demonstrate the manufacturing feasibility and safety, and to determine the maximum tolerated dose (MTD) of RNA-LP vaccines in adult ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0092867424003982

RNA aggregates harness the danger response for potent ... RNA-LPAs induced anti-tumor efficacy against the physiologically relevant antigen pp65 (overexpressed in human glioblastoma) in animals bearing ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04573140

NCT04573140 | A Study of RNA-lipid Particle (RNA-LP) ... This is a first in human Phase I study of RNA-LP vaccines for newly diagnosed adult MGMT unmethylated (low level or undetected) glioblastoma (GBM) and pediatric ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06389591

NCT06389591 | RNA-Lipid Particle (RNA-LP) Vaccines for ... This is a first in human Phase I study of RNA-LP vaccines for recurrent adult glioblastoma. Participants will receive two study drug products.

8. trials.braintumor.org trials.braintumor.org/trials/NCT05660408

RNA Lipid Particles Targeting Pediatric Recurrent Intracranial ... In this study, we will investigate the manufacturing feasibility, safety and immunologic activity of RNA-LP vaccine in patients with recurrent pulmonary or ...