RNA-Lipid Particle Vaccines for Brain Cancer

(PNOC020 rMB Trial)

Overseen By Jannerfer An

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Florida

Must be taking: Antiepileptics

Disqualifiers: Diffuse glioma, Bulky disease, HIV, others

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

Compensation: Varies

Number of Visits: 21

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new RNA-LP vaccine as a potential treatment for children and young adults with Medulloblastoma, a type of brain cancer that has recurred or worsened. The main goal is to determine the vaccine's safety and establish the maximum dosage that can be administered without causing excessive side effects. Participants must have previously received radiation therapy and have a confirmed case of relapsed Medulloblastoma. Those with two or more relapses or ongoing severe health issues may not qualify for this trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

Is there any evidence suggesting that the RNA-LP Vaccine is likely to be safe for humans?

Research has shown that RNA-lipid particle (RNA-LP) vaccines are generally well-tolerated in early studies. In trials for glioblastoma, a type of brain tumor, these vaccines have shown promise without causing serious side effects. Early-phase clinical trials found that mRNA vaccines, similar to RNA-LP vaccines, are safe and can trigger strong immune responses in patients.

These trials aimed to find the best dose while monitoring potential side effects. So far, researchers have tested RNA-LP vaccines in adults with brain cancer, and the results have been encouraging. Participants in these studies have not reported any major negative effects linked to the vaccine, suggesting it could be safe for wider use.

The current trial is in the early phase, focusing on ensuring the treatment's safety and determining the right dosage. Early-phase trials usually involve a small number of people and are crucial for proving a treatment's safety. So far, the data suggests that RNA-LP vaccines are a promising and safe option for treating brain cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Most treatments for recurrent or progressive Medulloblastoma, like surgery, radiation, and chemotherapy, aim to remove or kill cancer cells directly. But the RNA-Lipid Particle (RNA-LP) Vaccine works differently, targeting the immune system to recognize and attack brain cancer cells. This vaccine uses RNA encased in lipid particles to deliver instructions to the body, potentially leading to a more precise and robust immune response. Researchers are excited about this approach because it could offer a more targeted and less toxic alternative to conventional treatments, possibly improving outcomes for patients with fewer side effects.

What evidence suggests that the RNA-LP Vaccine might be an effective treatment for Medulloblastoma?

This trial will evaluate RNA-lipid particle (RNA-LP) vaccines for treating recurrent/progressive Medulloblastoma (rMB). Studies have shown that RNA-LP vaccines could be promising for treating brain cancers like glioblastoma. These vaccines use mRNA to teach the body's immune system to attack cancer cells. In early research, patients with solid tumors showed some positive immune responses after using similar vaccines. Although specific results for medulloblastoma (a type of childhood brain cancer) are not yet available, encouraging outcomes in other brain cancers suggest potential. The goal is to determine if these vaccines can help the immune system fight off medulloblastoma, similar to previous studies with glioblastoma. ^{1 6 7 8 9}

Who Is on the Research Team?

Sabine Mueller, MD, PhD

Principal Investigator

University of California, San Francisco

Elias Sayour, MD, PhD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

Inclusion Criteria

I am between 4 and 39 years old.

My medulloblastoma has come back or gotten worse for the first or second time.

I have had required MRI scans of my brain and spine before and after surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Surgery

Surgical resection with confirmatory pathologic diagnosis and sterile collection of tumor material

1 week

1 visit (in-person)

Salvage Therapy

Radiation and/or chemotherapy administered as salvage therapy

4 weeks

Multiple visits (in-person)

Immunotherapy

Participants receive three RNA-LP vaccines every 2 weeks followed by 12 cycles of adjuvant monthly RNA-LP vaccines

14 months

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with MRI and clinical evaluation every 3 months

12 months

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• RNA-LP Vaccine

How Is the Trial Designed?

Group I: recurrent/progressive Medulloblastoma (rMB) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Pediatric Neuro-Oncology Consortium

Collaborator

Citations

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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 ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12434405/

Promising Cancer Vaccine for Glioblastoma Therapy - PMC

The median OS was 394 days (13.0 months) (95% CI 309–648). The overall immune‐related response rate in solid tumor patients was 7.5% (95% CI 2.6 ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0168365925010867

Enhancing lipid nanoparticles-mediated RNA delivery to ...

GBM, the WHO grade IV GBM, accounts for ∼49 % of adult malignant brain tumors, with a 5-year survival rate of only 7.2 % [12,13]. Its formation ...

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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.

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cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-10211

RNA-Lipid Particle Vaccines for the Treatment of Patients ...

This phase I trial tests the safety, side effects and best dose of two ribonucleic acid-lipid particle (RNA-LP) vaccines for the treatment of patients with ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11433450/

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Early-phase clinical trials have indicated that mRNA vaccines are safe and can induce robust immune responses in GBM patients.

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withpower.com

withpower.com/trial/phase-1-recurrence-11-2024-3e836

RNA-Lipid Particle Vaccines for Recurrent Glioblastoma

This trial aims to explore the safety and optimal dose of a new RNA-Lipid Particle vaccine for individuals with recurrent glioblastoma, a type of brain cancer.

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RNA-Lipid Particle (RNA-LP) Vaccines for... | Clinical Trial

This is a first in human Phase I study of RNA-LP vaccines for recurrent adult glioblastoma. Participants will receive two study drug ...