RNA-LP Vaccine for Glioblastoma

(PNOC020 Trial)

Recruiting in Palo Alto (17 mi)

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of Florida

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: HIV, Hepatitis, Metastatic disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The primary objective will be to demonstrate the manufacturing feasibility and safety, and to determine the maximum tolerated dose (MTD) of RNA-LP vaccines in (Stratum 1) adult patients with newly diagnosed GBM (MGMT low level or unmethylated in adults only) and (Stratum 2) in pediatric patients with newly diagnosed HGG (pHGG). Funding Source - FDA OOPD

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, participants who require high doses of corticosteroids must reduce them to lower levels within one week before vaccination.

What data supports the effectiveness of the RNA-LP Vaccine for Glioblastoma treatment?

Research shows that similar mRNA-based vaccines can trigger strong immune responses against tumors, as seen in studies where mRNA vaccines protected mice from melanoma and enhanced immune responses in glioblastoma patients. The use of DOTAP liposomes as an adjuvant has also been shown to boost immune responses in mice, suggesting potential effectiveness in cancer immunotherapy. ^{1 2 3 4 5}

Is the RNA-LP Vaccine for Glioblastoma safe for humans?

The RNA-LP vaccine has been shown to be safe in both animal studies and an early human trial for glioblastoma, with no significant safety concerns reported. ^{1 4 6 7 8}

What makes the RNA-LP Vaccine for Glioblastoma unique compared to other treatments?

The RNA-LP Vaccine for Glioblastoma is unique because it uses a novel delivery system that enhances the immune response by forming 'onion-like' multi-lamellar RNA-lipid particle aggregates, which mimic infectious particles and activate immune cells to target the tumor. This approach differs from traditional mRNA vaccines by stimulating specific intracellular receptors and reprogramming the tumor environment to boost therapeutic T cell activity. ^{1 2 9 10 11}

Research Team

Elias Sayour, MD, PhD

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for adults over 21 with newly diagnosed GBM (a type of brain tumor) that hasn't spread, and whose tumors are not responsive to certain DNA repair mechanisms (MGMT unmethylated). Participants must be in good health post-surgery, have adequate organ function, and agree to use contraception. Those with prior treatments for head/neck cancer or other invasive malignancies within the last 3 years, active infections or immune diseases, severe medical conditions, or who are pregnant/breastfeeding cannot join.

Inclusion Criteria

I have given or my legal representative has given consent for me to participate.

For women of childbearing potential (WOCBP), negative serum/urine pregnancy test at enrollment (test will be repeated within 72 hours prior to starting TMZ in Stratum 1 patients)

WOCBP must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug

Exclusion Criteria

Known HIV, Hepatitis B, or Hepatitis C seropositive

My cancer has spread to the brain or beyond.

My cancer has spread to other parts of my body or the lining of my brain and spinal cord.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Surgery

Surgical resection for collection of tumor material for RNA extraction

1 week

1 visit (in-person)

Radiation

Standard of care radiation therapy following surgery

4 weeks

Multiple visits (in-person)

Immunotherapy

Participants receive RNA-LP vaccines, starting with 3 vaccines every 2 weeks, followed by 12 monthly vaccines

14 months

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 30 months

Every 3 months for the first year, then every 6-12 months

Treatment Details

Interventions

• Autologous total tumor mRNA and pp65 full length (fl) lysosomal associated membrane protein (LAMP) mRNA loaded DOTAP liposome vaccine (Cancer Vaccine)

Trial Overview The study tests RNA-LP vaccines made from a patient's own tumor mRNA against GBM. It aims to find the highest dose patients can tolerate without serious side effects (MTD), ensure it's safe to make and give these vaccines intravenously. The vaccine is designed to teach the body’s immune system to recognize and attack the tumor.

Participant Groups

Group I: Phase I pediatric (Stratum 2) Experimental Treatment 1 Intervention

A maximum of 24 adult patients will be enrolled in dose-escalation study using 3+3 study design.

Group II: Phase I adult (Stratum 1) Experimental Treatment 1 Intervention

A maximum of 28 adult patients will be enrolled in dose-escalation study using the BOIN design with an initial embedded accelerated titration design (ATD).

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UF Health Gainesville, FL

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1428

Patients Recruited

987,000+

Team Jack Foundation

Collaborator

Trials

2

Patients Recruited

100+

Florida Department of Health

Collaborator

Trials

30

Patients Recruited

13,000+

University of California, San Francisco

Collaborator

Trials

2636

Patients Recruited

19,080,000+

CureSearch

Collaborator

Trials

3

Patients Recruited

130+

Pacific Pediatric Neuro-Oncology Consortium

Collaborator

Trials

16

Patients Recruited

840+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Patients Recruited

1,553,000+

Findings from Research

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of a cationic complexes loaded with mRNA and α-Galactose ceramide enhances antitumor immunity and affects the tumor immune microenvironment. Guo, J., Ma, S., Mai, Y., et al.[2023]

Fusogenic liposomes (FLs) effectively deliver tumor cell-lysate (TCL) for both ex vivo dendritic cell-based vaccination and in vivo direct immunization, showing promise in targeting a broader range of tumor-associated antigens (TAAs).

In a murine model of melanoma, ex vivo dendritic cell-mediated vaccination demonstrated a more potent anti-tumor effect compared to direct immunization, indicating that this method may enhance the efficacy of cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine efficacy of fusogenic liposomes containing tumor cell-lysate against murine B16BL6 melanoma. Yoshikawa, T., Okada, N., Tsujino, M., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of a cationic liposome formulation (DOTAP) mixed with a recombinant tumor-associated antigen to induce immune responses and protective immunity in mice. Bei, R., Guptill, V., Masuelli, L., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mRNA-based cancer vaccine: prevention of B16 melanoma progression and metastasis by systemic injection of MART1 mRNA histidylated lipopolyplexes. Mockey, M., Bourseau, E., Chandrashekhar, V., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical implication of cellular vaccine in glioma: current advances and future prospects. Yan, Y., Zeng, S., Gong, Z., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conjugates of aberrant gangliosides in antiglioma vaccine: toxicological assay. Lombardi, V., Shnaar, R., Minev, B., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients. Migliorini, D., Dutoit, V., Allard, M., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. Butts, C., Murray, N., Maksymiuk, A., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the Therapeutic Efficacy of Glioma Vaccines Based on Allo- and Syngeneic Antigens and Distinct Immunological Costimulation Activators. Stathopoulos, A., Pretto, C., Devillers, L., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating the Fate of MP1000-LPX In Vivo by Adding Serum to Transfection Medium. He, S., Xia, S., Song, X., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

mRNA aggregates harness danger response for potent cancer immunotherapy. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Combination of a cationic complexes loaded with mRNA and α-Galactose ceramide enhances antitumor immunity and affects the tumor immune microenvironment. [2023]

3. Japan pubmed.ncbi.nlm.nih.gov

Vaccine efficacy of fusogenic liposomes containing tumor cell-lysate against murine B16BL6 melanoma. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

The use of a cationic liposome formulation (DOTAP) mixed with a recombinant tumor-associated antigen to induce immune responses and protective immunity in mice. [2021]

5. England pubmed.ncbi.nlm.nih.gov

mRNA-based cancer vaccine: prevention of B16 melanoma progression and metastasis by systemic injection of MART1 mRNA histidylated lipopolyplexes. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Clinical implication of cellular vaccine in glioma: current advances and future prospects. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Conjugates of aberrant gangliosides in antiglioma vaccine: toxicological assay. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Randomized phase IIB trial of BLP25 liposome vaccine in stage IIIB and IV non-small-cell lung cancer. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Exploring the Therapeutic Efficacy of Glioma Vaccines Based on Allo- and Syngeneic Antigens and Distinct Immunological Costimulation Activators. [2021]

11. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Investigating the Fate of MP1000-LPX In Vivo by Adding Serum to Transfection Medium. [2021]