RNA-Lipid Particle Vaccines for Recurrent Glioblastoma

Overseen By Phuong Deleyrolle

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Florida

Must not be taking: Bevacizumab, Live vaccines

Disqualifiers: Active infection, Uncontrolled seizures, AIDS, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 17 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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. The study includes two groups: one receiving the vaccine before surgery and the other after surgery, with both groups receiving additional monthly vaccine doses. It suits individuals who have previously been treated for glioblastoma, are at least 90 days past radiation treatment, and are ready for another surgery. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must be weaned off steroids or onto a low dose at the time of enrollment, and you cannot have received any live vaccines within 30 days prior to enrollment.

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

Research shows that RNA-Lipid Particle (RNA-LP) vaccines offer a new approach for treating glioblastoma. In earlier studies, researchers tested these vaccines in humans for the first time. Early results suggest they might be safe and manageable for patients with recurring glioblastoma. However, since this is their first human trial, detailed information about safety and side effects remains limited. As trials progress, researchers are closely monitoring for any negative reactions to better understand the vaccines' safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RNA-Lipid Particle (RNA-LP) vaccines for recurrent glioblastoma because they offer a novel approach to treating this aggressive brain cancer. Unlike traditional treatments like surgery, radiation, and chemotherapy, which can be limited in targeting cancer cells specifically, RNA-LP vaccines work by using RNA to instruct the body's immune system to recognize and attack tumor cells. This targeted action might not only enhance effectiveness but also reduce side effects associated with broader, systemic treatments. Additionally, these vaccines are designed to adapt to the unique mutations present in each tumor, potentially offering a more personalized and precise treatment option.

What evidence suggests that RNA-Lipid Particle Vaccines could be effective for recurrent glioblastoma?

This trial will compare two approaches using RNA-Lipid Particle (RNA-LP) vaccines for treating recurrent glioblastoma. Studies have shown that mRNA vaccines, including RNA-LP vaccines, hold promise for treating glioblastoma, a type of brain cancer. These vaccines help the immune system learn to identify and attack cancer cells. Research shows that RNA-LP vaccines are adaptable, can be produced quickly, and can trigger a strong immune response. Early results suggest they may be safe and tolerable for patients with recurring glioblastoma. However, clinical studies are ongoing to fully understand their effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Ashley Ghiaseddin, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for adults with recurrent glioblastoma, a type of brain cancer. Participants must have evidence of tumor recurrence after standard treatments. Specific eligibility criteria are not provided here.

Inclusion Criteria

It has been over 90 days since my last radiation treatment.

Bone Marrow: ANC (Absolute neutrophil count) ≥ 1,500µl (unsupported), Platelets ≥ 100/µl (unsupported for at least 3 days), Hemoglobin > 8 g/dL

Any side effects from my previous treatments have mostly gone away.

Exclusion Criteria

I am currently being treated for an infection or have a disease that weakens my immune system.

My cancer has come back in more than one area, but the original cancer site is stable.

My tumor is located in the brainstem or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 15 RNA-LP vaccines, with the first three being pp65 RNA-LP vaccines followed by monthly full dose RNA-LPs

17 months

Monthly visits for vaccine administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including up to 4 additional MRIs

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RNA-Lipid Particle (RNA-LP) Vaccines

Trial Overview The study is testing two types of RNA-Lipid Particle (RNA-LP) vaccines: pp65 RNA loaded lipid particles (DP1) and another set of RNA loaded lipid particles (DP2). It aims to find the highest dose patients can tolerate without severe side effects.

How Is the Trial Designed?

Group I: Arm 2: pp65 RNA-LPs (DP1) after biopsy Experimental Treatment 2 Interventions

Randomized 1:1 to receive pp65 RNA-LPs (DP1) starting after tumor biopsy/resection. All patients will receive three pp65 RNA-LP vaccines (DP1) before receiving full dose monthly RNA-LPs (RNA loaded lipid particles, RNA-LPs, DP2).

Group II: Arm 1: pp65 RNA-LPs (DP1) before biopsy Experimental Treatment 2 Interventions

Randomized 1:1 to receive pp65 RNA-LPs (DP1) starting before tumor biopsy/resection. All patients will receive three pp65 RNA-LP vaccines (DP1) before receiving full dose monthly RNA-LPs (RNA loaded lipid particles, RNA-LPs, DP2).

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Recent advances in immunotherapy for glioblastomas (GBM) focus on developing neoantigen vaccines and immune modulators, which could improve treatment outcomes for this aggressive cancer.

Combining mRNA vaccines with personalized medicine approaches may enhance the effectiveness of therapies, particularly in overcoming the resistance of GBM to traditional immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced immunotherapies for glioblastoma: tumor neoantigen vaccines in combination with immunomodulators. Segura-Collar, B., Hiller-Vallina, S., de Dios, O., et al.[2023]

RNA-based immunotherapies, particularly RNA dendritic cell vaccines, have shown safety in a small phase I clinical trial for treating glioblastoma (GBM), which is a highly lethal brain tumor.

RNA nanoparticle therapies are being developed and will soon be tested in GBM patients, indicating a promising new approach to improve treatment outcomes for this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contemporary RNA Therapeutics for Glioblastoma. Melnick, K., Dastmalchi, F., Mitchell, D., et al.[2022]

A vaccine using bone marrow-derived dendritic cells loaded with RNA from GL261 glioma cells successfully induced a specific T cell response and provided protection against brain tumors in mice.

The effectiveness of this vaccine was enhanced by adding recombinant interleukin-12, which suggests that combining immunotherapy with cytokines could improve treatment outcomes for intracranial malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dendritic cell vaccine induces protective immunity to intracranial growth of glioma. Insug, O., Ku, G., Ertl, HC., et al.[2021]

A new method using lipid-particle delivery systems to enhance the immunogenicity of tumor-derived mRNA has shown promise in mobilizing immune cells and rejecting tumors in murine models, indicating its potential for cancer immunotherapy.

In a first-in-human trial for glioblastoma patients, RNA-LPAs successfully induced pro-inflammatory responses and expanded T cell immunity, suggesting they could be effective in treating poorly immunogenic tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mRNA aggregates harness danger response for potent cancer immunotherapy. Mendez-Gomez, HR., DeVries, A., Castillo, P., et al.[2023]

Immunotherapy shows promise in treating glioblastoma by targeting cancer cells precisely while sparing healthy tissue, which could lead to better patient outcomes.

Various vaccination strategies, including peptide vaccines and dendritic cell vaccines, are being tested in clinical trials, indicating a growing interest in integrating these innovative therapies into standard treatment for glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine strategies for glioblastoma: progress and future directions. Jackson, C., Ruzevick, J., Brem, H., et al.[2021]

Dendritic cell (DC) vaccination has been shown to be safe and non-toxic in early phase trials for treating glioblastoma multiforme (GBM), suggesting a promising new immunotherapy approach.

Pre-clinical studies in mice demonstrated that DCs loaded with glioblastoma proteins significantly increased survival rates, supporting the potential for clinical trials in patients with GBM who do not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic cells pulsed with glioma lysates induce immunity against syngeneic intracranial gliomas and increase survival of tumor-bearing mice. Pellegatta, S., Poliani, PL., Corno, D., et al.[2006]

Anti-gene vaccines targeting the growth factor IGF-I, specifically using antisense (AS) and triple helix (TH) approaches, have been shown to significantly increase median survival in glioblastoma (GBM) patients, with some patients surviving up to 2-3 years.

The TH vaccines demonstrated stronger immunogenicity and a more robust immune response compared to AS vaccines, leading to improved outcomes in terms of patient survival, with median survival extending to 17-18 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Gene IGF-I Vaccines in Cancer Gene Therapy: A Review of a Case of Glioblastoma. Trojan, A., Lone, YC., Briceno, I., et al.[2023]

Dendritic cell (DC)-based vaccines pulsed with tumor extracts or RNA significantly enhanced G422-specific cytotoxic T lymphocyte (CTL) responses in a mouse model of glioblastoma, indicating a strong immune activation.

Vaccination with these pulsed DCs not only improved CTL responses but also significantly prolonged survival in mice with glioblastoma, suggesting that this approach could be an effective therapeutic strategy against gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of intracranial G422 glioblastoma with dendritic cells pulsed with tumor extract or RNA. Zhang, Z., Tang, LL., Zhan, RY., et al.[2018]

Citations

1. 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.

2. 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 ...

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

Personalized mRNA vaccines in glioblastoma therapy This review focuses on the emerging use of mRNA vaccines for GBM treatment. We summarize recent advancements, evaluate current obstacles, and discuss notable ...

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

Promising Cancer Vaccine for Glioblastoma Therapy mRNA vaccines are promising due to their flexibility, rapid production, and strong immune activation, though clinical investigation is ongoing.

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

RNA-Lipid Particle Vaccines for the Treatment of Patients ... These two RNA-LP vaccines may be safe and tolerable in treating patients with recurrent glioblastoma. Eligibility Criteria ...

6. academic.oup.com academic.oup.com/noa/article/7/Supplement_4/iv72/8249866

Translational advancements in tumor vaccine therapies for ... A Study of RNA-lipid Particle (RNA-LP) Vaccines for Newly Diagnosed Pediatric High-Grade Gliomas (pHGG) and Adult Glioblastoma (GBM) (PNOC020) ...