[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06389591":3,"trial-entities:NCT06389591":139,"trial-summary:NCT06389591":143},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":20,"study_type":25,"primary_purpose":26,"phases":27,"enrollment_info":29,"interventions":32,"primary_outcomes":43,"secondary_outcomes":52,"sex":53,"minimum_age":54,"maximum_age":55,"healthy_volunteers":56,"eligibility_criteria":57,"std_ages":106,"locations":109,"central_contacts":128,"overall_officials":131,"references":133,"see_also_links":138},"NCT06389591","202301957","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)","RECRUITING","2027-12-01","2026-05","2026-05-15","2024-12-02","University of Florida","OTHER",true,"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.","This is a first in human Phase I study of RNA-LP vaccines for recurrent adult glioblastoma. Participants will receive two study drug products. The first, pp65 RNA-LP, is a messenger RNA (mRNA) pp65 vaccine given for the first 3 vaccines to try to change how the tumor behaves. The second study drug RNA-LP, given as monthly vaccines 4-15, includes pp65 mRNA and tumor RNA from each patient's tumor tissue.\n\nPatients will may receive up to three pp65 RNA-LP vaccines (DP1) before receiving full dose monthly RNA-LPs (RNA loaded lipid particles, RNA-LPs, DP2). All participants will receive the same number of vaccines, up to 15.\n\nThe immunotherapy with RNA lipid particle (RNA-LP) vaccines is the treatment portion of this study. During this study, we will make, test and give the RNA-LP vaccine therapy. As part of this study, participants will undergo up to 4 additional MRIs.",[19],"Recurrent Glioblastoma",[21,22,23,24],"brain tumor","malignant brain tumor","immunotherapy","adult","INTERVENTIONAL","TREATMENT",[28],"PHASE1",{"count":30,"type":31},24,"ESTIMATED",[33,39],{"type":34,"name":35,"description":36,"armGroupLabels":37},"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",[38],"Arm 1: pp65 RNA-LPs (DP1) before biopsy",{"type":34,"name":40,"description":41,"armGroupLabels":42},"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",[38],[44,48],{"measure":45,"description":46,"timeFrame":47},"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\u002FQc 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",{"measure":49,"description":50,"timeFrame":51},"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",[],"ALL","18 Years","80 Years",false,{"inclusion":58,"exclusion":85,"raw_text":105},[59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84],"Age \\>\u002F= 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 completed Fractionated Radiation therapy as frontline treatment for primary disease, either alone or with concurrent therapy (including temozolomide or another systemic chemotherapy agent). Patients must be at least 12 weeks post chemoradiation completion.","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\u002Fbiopsy 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\u002Fµl (unsupported for at least 3 days)","Hemoglobin \\> 8 g\u002FdL","Renal:","BUN ≤ 25 mg\u002Fdl","Creatinine ≤ 1.7 mg\u002Fdl","Hepatic","Bilirubin ≤ 2.0 mg\u002Fdl","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\u002Furine 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.",[86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104],"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\u002FFLAIR 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\u002For 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\u002For 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","Inclusion Criteria:\n\n* Age \\>\u002F= 18years\n* Histopathologically proven GBM using the 2021 WHO Classification of Tumors of the CNS (WHO CNS5).\n* Unequivocal evidence of tumor progression as documented by brain MRI scan per RANO criteria.\n* Tumor must have a primary supratentorial component at the time of disease progression.\n* Patients must have received surgery and completed Fractionated Radiation therapy as frontline treatment for primary disease, either alone or with concurrent therapy (including temozolomide or another systemic chemotherapy agent). Patients must be at least 12 weeks post chemoradiation completion.\n* Patient must be at least 90 days from completion of prior radiation\n* 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\n* Patient must be either weaned off steroids or weaned onto physiologic dosing at the time of enrollment.\n* Patient must be a candidate for surgery\u002Fbiopsy 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).\n* 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.\n* 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.\n* Bone Marrow:\n\n  * ANC (Absolute neutrophil count) ≥ 1,500µl (unsupported)\n  * Platelets ≥ 100\u002Fµl (unsupported for at least 3 days)\n  * Hemoglobin \\> 8 g\u002FdL\n* Renal:\n\n  * BUN ≤ 25 mg\u002Fdl\n  * Creatinine ≤ 1.7 mg\u002Fdl\n* Hepatic\n\n  * Bilirubin ≤ 2.0 mg\u002Fdl\n  * ALT ≤ 5 times institutional upper limits of normal for age\n  * AST ≤ 5 times institutional upper limits of normal for age\n* Patient must be able to give consent.\n* For women of childbearing potential (WOCBP), negative serum\u002Furine pregnancy test at enrollment.\n* 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.\n* 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.\n\nExclusion Criteria:\n\n* Patients who received prior treatment with bevacizumab.\n* Known active infection (requiring treatment by antiviral or antibiotics) or immunosuppressive disease.\n* Patients with multifocal recurrent disease characterized by more than one enhancing lesion separated by noncontiguous T2\u002FFLAIR signal abnormality. Patients with recurrence outside of the original tumor site are eligible if there is stability at the original site of disease.\n* Patients with uncontrolled seizure disorders\n* Any patients that have received any live vaccines within 30 days prior to enrollment\n* Tumors with primary localization to the brainstem or spinal cord\n* Severe, active co-morbidity, defined as follows:\n\n  * Unstable angina and\u002For congestive heart failure requiring hospitalization.\n  * Unstable cardiac arrhythmias, abnormalities, or transmural myocardial infarction within the last 6 months.\n  * Acute bacterial or fungal infection requiring intravenous treatment at study treatment.\n  * Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at study treatment\n  * Hepatic insufficiency resulting in clinical jaundice and\u002For coagulation defects.\n  * 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.\n  * Patients with autoimmune disease requiring medical management with immunosuppressants.\n  * Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.\n  * 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.\n* Women of childbearing potential must not be pregnant or breast-feeding.\n* 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.\n* Participants who are unwilling or unable to receive treatment and undergo follow-up evaluations",[107,108],"ADULT","OLDER_ADULT",[110],{"facility":111,"status":8,"city":112,"state":113,"zip":114,"country":115,"contacts":116,"geoPoint":125},"UF Health","Gainesville","Florida","32608","United States",[117,122],{"name":118,"role":119,"phone":120,"email":121},"Phuong Deleyrolle","CONTACT","352-273-5519","wells-btc@ufl.edu",{"name":123,"role":124},"Ashley Ghiaseddin, MD","PRINCIPAL_INVESTIGATOR",{"lat":126,"lon":127},29.65163,-82.32483,[129],{"name":118,"role":119,"phone":120,"email":130},"wells-BTC@ufl.edu",[132],{"name":123,"affiliation":13,"role":124},[134],{"pmid":135,"type":136,"citation":137},"41218853","DERIVED","Carrera-Justiz S, Aghaee M, Qdaisat S, Weidert F, Garcia GA, Fagman L, Zhang D, Stover B, Moor RSF, Xie C, Goldenberg E, von Roemeling C, Doonan B, Chardon-Robles J, Elliott L, Sawyer WG, Deleyrolle LP, Sahay B, Foster TP, Seligson ND, Rahman M, Ghiaseddin A, Castillo P, Lee JH, Silver NL, Doty A, Ligon JA, Milner RJ, Mitchell D, Mendez-Gomez H, Moore H, Sayour EJ. Systemic mRNA vaccines elicit rapid immune activation in canine brain tumors. J Immunother Cancer. 2025 Nov 11;13(11):e011817. doi: 10.1136\u002Fjitc-2025-011817.",[],{"nct_id":4,"conditions":140,"biomarkers":142},[141],"Glioblastoma",[],{"nct_id":4,"found":15,"summary":144,"prompt_version":154},{"design":145,"status":146,"heading":147,"summary":148,"follow_up":149,"word_count":150,"commitments":151,"compensation":152,"drugs_mentioned":153},"This is a Phase 1 study, meaning it's the first time these vaccines are being tested in humans. It will enroll 24 participants to evaluate safety and manufacturing feasibility.","completed","RNA-Lipid Particle (RNA-LP) Vaccines for Recurrent Glioblastoma","This study is testing RNA-Lipid Particle (RNA-LP) vaccines for adults with recurrent glioblastoma (a type of brain cancer). The goal is to see if these vaccines can be safely made and given, and to find the highest safe dose. You would receive two types of vaccines: first, pp65 RNA loaded lipid particles (DP1), and then personalized RNA loaded lipid particles (DP2) which include RNA from your own tumor. This treatment works by using your body's immune system (immunotherapy) to fight the cancer. To join, you must be between 18 and 80 years old, have glioblastoma that has returned, and show clear signs of tumor growth on an MRI. The study is currently unclear about its recruitment status and plans to enroll 24 participants.","Your safety will be monitored from the first vaccine until 30 days after the last dose, for up to 17 months.",123,"You would receive up to 15 vaccines intravenously. You would also undergo up to 4 additional MRI scans.","Not stated in the trial record.",[],null]