RNA-Lipid Particle (RNA-LP) Vaccines for Recurrent Adult Glioblastoma (GBM)

A Phase I Study of RNA-Lipid Particle (RNA-LP) Vaccines for Recurrent Adult Glioblastoma (GBM)

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 patients with recurrent glioblastoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent Glioblastoma
• Intervention / Treatment: Biological: pp65 RNA loaded lipid particles, pp65 RNA-LPs (Drug Product 1 or DP1); Biological: RNA loaded lipid particles, RNA-LPs (Drug Product 2 or DP2)

Detailed Description

This is a first in human Phase I study of RNA-LP vaccines for recurrent adult glioblastoma. Patients will be randomized 1:1 to receive RNA-LP starting either before (Arm 1) or after tumor biopsy/resection (Arm 2).

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Marcia Hodik; Phone Number: 352-273-9000; Email: marcia.hodik@neurosurgery.ufl.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • UF Health
      • Principal Investigator: Ashley Ghiaseddin, MD
      • Contact: Marcia Hodik; Phone Number: 352-273-9000; Email: marcia.hodik@neurosurgery.ufl.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >/= 18years
• Histopathologically proven recurrent GBM using the 2021 WHO Classification of Tumors of the CNS (WHO CNS5).
• Tumor must have a primary supratentorial component
• Patients must have received surgery and radiotherapy as frontline treatments for primary disease
• Patient must be at least 90 days from completion of prior radiation
• Any adverse events patient has experienced from prior therapy must have resolved to ≤ Gr. 1 according to CTCAE (NCI Common Terminology Criteria for Adverse Events) v5.0 prior to enrollment
• Patient must be either weaned off steroids or weaned onto physiologic dosing at the time of enrollment.
• Patient must be a candidate for surgery/biopsy as acceptable standard of care for sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles (LPs).
• A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively and postoperatively. Pre-op MRI must be performed within 28 days prior to study enrollment.
• Performance Score: (KPS/LS) ≥ 60. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

• Bone Marrow:

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

• Renal:

  • BUN ≤ 25 mg/dl
  • Creatinine ≤ 1.7 mg/dl

• Hepatic

  • Bilirubin ≤ 2.0 mg/dl
  • ALT ≤ 5 times institutional upper limits of normal for age
  • AST ≤ 5 times institutional upper limits of normal for age
• Signed informed consent. If the patient's age or mental status precludes his/her giving informed consent, written informed consent may be given by a legally authorized representative.
• For women of childbearing potential (WOCBP), negative serum/urine pregnancy test at enrollment.
• 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. Refer to Appendix B for definition of WOCBP and guidance on acceptable contraceptive methods.
• Males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.

Exclusion Criteria:

• Known active infection (requiring treatment by antiviral or antibiotics) or immunosuppressive disease.
• Patients with multifocal recurrent disease characterized by more than one enhancing lesion separated by noncontiguous T2/FLAIR signal abnormality. Patients with recurrence outside of the original tumor site are eligible if there is stability at the original site of disease.
• Patients with uncontrolled seizure disorders
• Any patients that have received any live vaccines within 30 days prior to enrollment
• Tumors with primary localization to the brainstem or spinal cord

• Severe, active co-morbidity, defined as follows:

  • Unstable angina and/or congestive heart failure requiring hospitalization.
  • Unstable cardiac arrhythmias, abnormalities, or transmural myocardial infarction within the last 6 months.
  • Acute bacterial or fungal infection requiring intravenous treatment at study treatment.
  • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at study treatment
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
  • Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
  • Patients with autoimmune disease requiring medical management with immunosuppressants.
  • Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.
  • Pregnancy or women of childbearing potential and men who are sexually active and who are unwilling or unable to use an acceptable method of contraception for the entire study period; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
• Women of childbearing potential must not be pregnant or breast-feeding.
• Participants who are receiving any other investigational agents or who have been treated on any other therapeutic clinical protocols within 30 days prior to projected first dose of study treatment.
• Participants who are unwilling or unable to receive treatment and undergo follow-up evaluations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: pp65 RNA-LPs (DP1) before biopsy; 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).	Biological: pp65 RNA loaded lipid particles, pp65 RNA-LPs (Drug Product 1 or DP1); pp65 RNA loaded lipid particles or pp65 RNA-LPs administered intravenously; Biological: RNA loaded lipid particles, RNA-LPs (Drug Product 2 or DP2); personalized tumor mRNA, pp65 fl LAMP mRNA and DOTAP liposomes or RNA loaded lipid particles, RNA-LPs administered intravenously
Experimental: Arm 2: pp65 RNA-LPs (DP1) after biopsy; 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).	Biological: pp65 RNA loaded lipid particles, pp65 RNA-LPs (Drug Product 1 or DP1); pp65 RNA loaded lipid particles or pp65 RNA-LPs administered intravenously; Biological: RNA loaded lipid particles, RNA-LPs (Drug Product 2 or DP2); personalized tumor mRNA, pp65 fl LAMP mRNA and DOTAP liposomes or RNA loaded lipid particles, RNA-LPs administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of vaccines meeting release criteria in the DLT window during the first three vaccines	Manufacturing feasibility will be determined based on the percentage of vaccines that are successfully manufactured in the DLT window during the first three vaccines. If two-thirds of vaccines are successfully manufactured with Qa/Qc clearance, the investigators will conclude that RNA-LPs can be successfully manufactured.	from the date of surgery until administration of third vaccine, up to 20 weeks
Incidence of investigational treatment related toxicities	AEs and SAEs must be reported begins at time of first investigational product is received and ends 30 days after last investigational product is given.	from first vaccine to 30 days after last dose of vaccine administered, up to 17 months

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Ashley Ghiaseddin, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence
• Other Study ID Numbers: OCR44973

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No