Virus-Based Gene Therapy (AdV-HSV1-TK and AdV-Flt3L) in Combination With Valacyclovir for the Treatment of Pediatric and Young Adult Patients With Resectable, Recurrent Primary Malignant Brain Tumors

NCT06914479 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: UMCC 2024.064NCI-2025-01951HUM00252291
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Resectable Brain Neoplasm; Recurrent Malignant Brain Neoplasm; Recurrent Diffuse Hemispheric Glioma, H3 G34-Mutant

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to day 21

Secondary Outcomes (4)

• Overall survival at 6 months (OS6)

  At 6 months

• OS time

  From study enrollment until death from any cause, up to 5 years

• Progression free survival at 6 months (PFS6)

  At 6 months after study enrollment

• PFS time

  From study enrollment until the occurrence of the first event (relapse, progression per RAPNO criteria, or death from any cause), up to 5 years

Study Arms (1)

Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir)

EXPERIMENTAL

Patients undergo standard of care tumor resection and receive AdV-HSV1-TK and AdV-Flt3L via multiple injections over 3-5 minutes each to areas around the tumor. One to three days after surgery, patients receive valacyclovir PO TID on days 1-14 of each cycle. Cycles repeat every 12 weeks for 5 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive standard of care radiation therapy starting on day 21. Patients undergo MRI and blood sample collection throughout the study.

Genetic: Ad-hCMV-Flt3L; Genetic: Ad-hCMV-TK; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Survey Administration; Procedure: Tumor Resection; Drug: Valacyclovir

Interventions

Ad-hCMV-Flt3L GENETIC

Given via injection

Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir)

Ad-hCMV-TK GENETIC

Given via injection

Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir)

Survey Administration OTHER

Ancillary studies

Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir)

Tumor Resection PROCEDURE

Undergo standard of care tumor resection

Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir)

Valacyclovir DRUG

Given PO

Also known as: Valaciclovir, ValACV, Zelitrex

Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir)

Eligibility Criteria

• Age: 3 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 3 to 25 years with:
• Diagnosis of malignant primary brain tumor after tumor recurrence, relapse, or progression who have completed up-front, standard-of-care therapy
• Age 26 to 39 years with:
• 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 m\^2)
• Participants who are receiving corticosteroids must be on a stable or decreasing dose for at least 3 days prior to baseline MRI
• Surgical resection of the tumor recurrence/relapse/progression is clinically indicated at the time of enrollment
• A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate
• Participant must be willing to provide archival formalin-fixed embedded (FFPE) and/or frozen tissue specimens, if available
• Participant must have recovered from all acute side effects of prior therapy.
• From the projected start of scheduled study treatment, the following time periods must have elapsed: At least 7 days after last dose of a biologic agent or beyond time during which adverse events are known to occur for a biologic agent, 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from antibody therapy (21 days for bevacizumab,.6 weeks from cellular therapy (i.e. modified T cells, natural killer \[NK\] cells, dendritic cells, etc.), or 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor therapies
• For participants who have received radiotherapy previously, participants must be at least 28 days from focal radiation therapy, at least 150 days from craniospinal irradiation therapy.
• The use of bevacizumab to control radiation therapy-induced edema is allowed prior to or during study therapy (if used for tumor-directed therapy, please see required washout period above).
• Dosing limitations are as follows:
• Bevacizumab (or bioequivalent) for up to a maximum of 5 doses, dosing per institutional standard. There is no required washout period

You may not qualify if:

• 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
• Ongoing therapy with valacyclovir that is unable to be stopped due to a medical condition
• Known allergy to valacyclovir
• Concurrent use of other investigational agents.
• Participants who are currently receiving another investigational drug. Investigational imaging agents or agents used to enhance tumor visibility on imaging or during tumor biopsy/resection should be discussed with the study chairs
• Participants who are currently receiving anti-cancer agents
• Participants with a known disorder that affects their immune system, such as HIV or hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy
• Presence of uncontrolled infection or other uncontrolled systemic illness
• Current diagnosis of bipolar disorder or major depressive disorder
• Presence of a congenital immune deficiency syndrome or acquired autoimmune disease
• Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine or serum pregnancy test prior to the start of therapy (as clinically indicated)
• Active illicit drug use or diagnosis of alcoholism

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (1)

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; Transurethral Resection of Bladder; Valacyclovir

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Andrea T Franson

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer AnswerLine

CONTACT

1-800-865-1125; CancerAnswerLine@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2025
• First Posted: April 6, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

US (1)