This phase I trial tests the safety, side effects and best dose of AdV-HSV1-TK and AdV-Flt3L in combination with valacyclovir for the treatment of patients with primary cancerous (malignant) brain tumors that can be removed by surgery (resectable) and that have come back after a period of improvement (recurrent). AdV-HSV1-TK and AdV-Flt3L use a virus modified in the laboratory to kill tumor cells and stimulate the immune system to recognize the tumor cells as "invaders" which can lead to tumor shrinkage. For this process to work, an oral anti-herpes medication called valacyclovir is also needed. Giving AdV-HSV1-TK, AdV-Flt3L and valacyclovir may be safe, tolerable and/or effective in treating patients with resectable, recurrent primary malignant brain tumors.
Diagnosis of malignant primary brain tumor after tumor recurrence, relapse, or progression who have completed up-front, standard-of-care therapy
Diagnosis of diffuse hemispheric glioma, H3 G34-mutant, per 2021 World Health Organization (WHO) classification, after tumor recurrence, relapse, or progression who have completed up-front, standard-of-care therapy
At least 10 kg (and body surface area [BSA] > 0.5 m²)
Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 3 days prior to baseline MRI
Patient deemed not clinically appropriate to undergo tumor tissue resection by a neurosurgeon
Evidence of disseminated disease, including diffuse leptomeningeal disease or evidence of cerebrospinal fluid (CSF) dissemination
Patient with primary brainstem or primary spinal tumors
History of prior gene therapy
Single group
Ad-hCMV-Flt3L
GeneticGiven via injection
Ad-hCMV-TK
GeneticGiven via injection
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Survey Administration
Other interventionAncillary studies
Tumor Resection
Procedure/SurgeryUndergo standard of care tumor resection
Valacyclovir
DrugGiven PO
Dose limiting toxicity (DLT)
Each participant will be classified as either having a DLT prior to Day 21 after dual vector administration or Day 21 after dual vector administration with no DLT (a binary endpoint). Adverse events (AEs) will be defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.
Overall survival at 6 months (OS6)
Defined as the percentage of participants alive at least 6 months (26 weeks) after the study enrollment. Will be addressed by using the Kaplan-Meier method with confidence intervals. Estimation of OS6 will be addressed by using the Kaplan-Meier method with confidence intervals (R module: 'survival').
OS time
Estimation of median OS will be addressed by using the Kaplan-Meier method with confidence intervals (R module: 'survival').
Progression free survival at 6 months (PFS6)
Defined as the percentage of participants alive and free from progression (relapse, progression per Response Assessment in Pediatric Neuro-Oncology \[RAPNO\] criteria, or death from any cause) at 6 months (26 weeks) after study enrollment. Estimation of PFS6 will be addressed by using the Kaplan-Meier method with confidence intervals (R module: 'survival'). Point estimates of PFS6 will be presented along with either standard error or 90% confidence intervals.
PFS time
Estimation of median PFS will be addressed by using the Kaplan-Meier method with confidence intervals (R module: 'survival').
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