RNA-Lipid Particle Vaccines for Recurrent Glioblastoma

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

This study is testing a new type of vaccine for adults with recurrent glioblastoma to see if it is safe and how well it works in treating their tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: University of Florida (Academic / other)
• Drugs / interventions: bevacizumab, Radiation, immunotherapy
• Locations: 1 site (Gainesville, Florida)
• Trial ID: NCT06389591 on ClinicalTrials.gov

What this trial studies

This Phase I study aims to evaluate the safety and manufacturing feasibility of RNA-Lipid Particle (RNA-LP) vaccines in adult patients with recurrent glioblastoma. Participants will receive two types of RNA-LP vaccines: the first is a pp65 mRNA vaccine administered prior to surgery, and the second includes both pp65 mRNA and tumor RNA from the patient's own tumor tissue, given monthly after surgery. The study will randomly assign participants to either group and monitor their response through up to 15 vaccinations and additional MRIs. The goal is to determine the maximum tolerated dose and assess how the treatment affects tumor behavior.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histopathologically confirmed recurrent glioblastoma who have completed prior treatments and meet specific eligibility criteria.

Not a fit: Patients who have not undergone prior surgery or radiation therapy, or those with significant unresolved adverse events from previous treatments, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a novel immunotherapy option for patients with recurrent glioblastoma, potentially improving their outcomes.

How similar studies have performed: While this approach is novel, other studies using mRNA-based immunotherapies have shown promise in various cancers, suggesting potential for success in this context.

Eligibility criteria

Inclusion Criteria:

* Age \>/= 18years
* Histopathologically proven GBM using the 2021 WHO Classification of Tumors of the CNS (WHO CNS5).
* Unequivocal evidence of tumor progression as documented by brain MRI scan per RANO criteria.
* Tumor must have a primary supratentorial component at the time of disease progression.
* Patients must have received surgery and and should have completed Fractionated Radiation therapy with concurrent temozolomide as frontline treatments for primary disease and be at least 12 weeks post chemoradiation completion.
* Patient must be at least 90 days from completion of prior radiation
* Patients with 2nd progression are eligible to participate
* 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) ≥ 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
* Patient must be able to give consent.
* 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.
* 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:

* Patients who received prior treatment with bevacizumab.
* 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

Where this trial is running

Gainesville, Florida

• UF Health — Gainesville, Florida, United States (Recruiting)

Study contacts

• Principal investigator: Ashley Ghiaseddin, MD — University of Florida
• Study coordinator: Phuong Deleyrolle

Conditions Recurrent Glioblastoma; brain tumor; malignant brain tumor; immunotherapy; adult