Virus-Based Gene Therapy + Valacyclovir for Brain Cancer

Overseen By Cancer AnswerLine

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Michigan Rogel Cancer Center

Must be taking: Valacyclovir

Must not be taking: Investigational drugs, Anti-cancer agents

Disqualifiers: Disseminated disease, Brainstem tumors, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 60 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new virus-based gene therapy combined with valacyclovir (an anti-herpes medication) for treating brain cancer. The goal is to determine if this combination is safe and effective in shrinking tumors by using a virus to kill cancer cells and activate the immune system. It targets individuals with recurring brain tumors that can be surgically removed. Suitable candidates have completed standard treatments but are experiencing tumor regrowth. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in humans.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that ongoing therapy with valacyclovir that cannot be stopped is an exclusion criterion. It also states that participants currently receiving anti-cancer agents or other investigational drugs are excluded.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that virus-based gene therapy using AdV-Flt3L and AdV-HSV1-TK, combined with the drug valacyclovir, is generally safe for people. So far, studies have not identified any major safety concerns. This treatment kills cancer cells and boosts the immune system's ability to fight cancer. Valacyclovir, typically used for herpes, supports this process. Although still in early testing stages, current evidence suggests the treatment is well-tolerated. However, further research is needed to fully understand any possible side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for brain cancer, which typically involve surgery, radiation, and chemotherapy, this new approach uses virus-based gene therapy. Researchers are excited because AdV-HSV1-TK and AdV-Flt3L are genetically engineered viruses designed to target and kill cancer cells while stimulating the immune system to fight the tumor more effectively. Additionally, the use of valacyclovir enhances the effectiveness of the viral therapy by activating the virus only in cancerous cells, minimizing damage to healthy cells. This innovative mechanism of action offers the potential for more precise and less toxic treatment outcomes compared to traditional methods.

What evidence suggests that this virus-based gene therapy and valacyclovir treatment might be effective for brain cancer?

In this trial, participants will receive a combination of AdV-HSV1-TK and AdV-Flt3L with the drug valacyclovir. Studies have shown that this combination may be promising for treating brain tumors. Research suggests that this treatment works by killing tumor cells and aiding the immune system in fighting the tumor. In a study using a model, this approach improved survival rates to about 70%. The treatment also reduced some symptoms caused by brain tumors. While more research is needed, these findings suggest this therapy could be effective for patients with recurring brain cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Andrea T Franson

Principal Investigator

University of Michigan Rogel Cancer Center

Are You a Good Fit for This Trial?

This trial is for pediatric and young adult patients with certain types of resectable, recurrent malignant brain tumors. Participants must be able to undergo surgery and take oral medication.

Inclusion Criteria

Peripheral absolute neutrophil count (ANC) ≥ 1000/mm^3 (1.0g/l)

I am mostly able to carry out daily activities.

I have been on a stable or decreasing dose of corticosteroids for at least 3 days.

Exclusion Criteria

Known allergy to valacyclovir

I must continue taking valacyclovir for a health issue.

Participants with a known disorder that affects their immune system

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo tumor resection and receive AdV-HSV1-TK and AdV-Flt3L via injections, followed by valacyclovir for 14 days per cycle. Cycles repeat every 12 weeks for 5 cycles.

60 weeks

Multiple visits for injections and monitoring

Radiation

Participants may receive standard of care radiation therapy starting on day 21.

Varies

Follow-up

Participants are monitored for safety and effectiveness after treatment, including MRI and blood sample collection.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• AdV-Flt3L
• AdV-HSV1-TK

Trial Overview The trial tests the safety and optimal dosage of two virus-based gene therapies (AdV-HSV1-TK and AdV-Flt3L) combined with valacyclovir, an anti-herpes drug, in shrinking or treating brain tumors.

How Is the Trial Designed?

Group I: Treatment (AdV-HSV1-TK , AdV-Flt3L and valacyclovir) Experimental Treatment 7 Interventions

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.

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Published Research Related to This Trial

Viruses are being explored as innovative therapies for malignant gliomas, serving both as vectors for delivering therapeutic genes and as agents that can selectively destroy tumor cells.

Current clinical trials have utilized retroviral and adenoviral vectors to enhance tumor susceptibility to treatments, as well as conditionally replicating HSV viruses, showing promise but indicating a need for further research into additional viral options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viruses in the treatment of brain tumors. Fecci, PE., Gromeier, M., Sampson, JH.[2019]

The study evaluated the safety and activity of two adenoviral vectors (Ad-hCMV-TK and Ad-hCMV-Flt3L) in 18 patients with high-grade glioma, showing that the treatment was well-tolerated with no dose-limiting toxicities observed.

The median overall survival for patients was 21.3 months, suggesting that this combination therapy is promising and warrants further investigation in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined cytotoxic and immune-stimulatory gene therapy for primary adult high-grade glioma: a phase 1, first-in-human trial. Umemura, Y., Orringer, D., Junck, L., et al.[2023]

Adenovirus-mediated gene therapy using the HSV-tk gene effectively treated brain tumors in a rat model, allowing tumor cells to convert ganciclovir into a toxic form, leading to complete tumor elimination in treated animals.

Rats receiving the ADV-tk gene therapy along with ganciclovir survived significantly longer (up to 120 days) compared to untreated rats, indicating a promising approach for enhancing survival in brain tumor patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adenovirus-mediated gene therapy of experimental gliomas. Perez-Cruet, MJ., Trask, TW., Chen, SH., et al.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06914479

Study Details | NCT06914479 | Virus-Based Gene Therapy ... Giving AdV-HSV1-TK, AdV-Flt3L and valacyclovir may be safe, tolerable and/or effective in treating patients with resectable, recurrent primary malignant brain ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2593113/

Flt3L in Combination With HSV1-TK-mediated Gene Therapy ... In this model, treatment with Ads expressing Fms-like tyrosine kinase 3 ligand (Flt3L), in combination with Ad-HSV1-TK improves the survival rate to ~70% and ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923001356

Oncolytic Viral Therapy for Malignant Glioma and Their ... Glioblastoma is the most common primary malignant brain tumor in adults and outcomes remain poor despite the current standard of care multimodal therapy.

4. trials.braintumor.org trials.braintumor.org/trials/NCT06914479

Virus-Based Gene Therapy (AdV-HSV1-TK and AdV-Flt3L) in ... 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 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/18283279/

Flt3L in combination with HSV1-TK-mediated gene therapy ... We demonstrate that the intracranial GBM induces behavioral deficits that are resolved after treatment with Ad-Flt3L/Ad-TK (+GCV).

6. withpower.com withpower.com/trial/phase-1-neoplasms-5-2025-3aaea

Virus-Based Gene Therapy + Valacyclovir for Brain Cancer Research on virus-based gene therapy using AdV-Flt3L and AdV-HSV1-TK for brain cancer shows it is generally safe in humans, with studies indicating no major ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9723031/

Oncolytic Viral Therapy for Malignant Glioma and Their ... Glioblastoma is the most common primary malignant brain tumor in adults and outcomes remain poor despite the current standard of care multimodal therapy.

8. academic.oup.com academic.oup.com/noa/article/2/1/vdaa013/5728539

Suicide gene therapy for the treatment of high-grade glioma Abstract. Suicide gene therapy has represented an experimental cancer treatment modality for nearly 40 years. Among the various cancers ...