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

11 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment AdV-Flt3L and AdV-HSV1-TK for brain cancer?

Research shows that using AdV-Flt3L and AdV-HSV1-TK together in animal models of brain cancer improved survival rates significantly and helped the immune system fight the tumor. This combination therapy also reversed behavioral problems caused by the tumor and restored normal brain structure, indicating its potential effectiveness and safety. ^{1 2 3 4 5}

Is the virus-based gene therapy with Valacyclovir safe for brain cancer treatment?

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 toxicities and a recovery of normal brain function in animal models. ^{1 2 3 5 6}

How is the Virus-Based Gene Therapy + Valacyclovir treatment for brain cancer different from other treatments?

This treatment is unique because it uses a virus to deliver genes directly into brain tumor cells, which then helps the immune system attack the cancer. It combines two components: one that makes cancer cells sensitive to a drug that kills them, and another that boosts the immune response, offering a novel approach compared to traditional treatments. ^{2 3 5 6 7}

Research Team

Andrea T Franson

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

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.

I have had gene therapy before.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A novel bicistronic high-capacity gutless adenovirus vector that drives constitutive expression of herpes simplex virus type 1 thymidine kinase and tet-inducible expression of Flt3L for glioma therapeutics. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Flt3L in combination with HSV1-TK-mediated gene therapy reverses brain tumor-induced behavioral deficits. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Flt3L in Combination With HSV1-TK-mediated Gene Therapy Reverses Brain Tumor-induced Behavioral Deficits. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Viruses in the treatment of brain tumors. [2019]

5. England 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Flt3L and TK gene therapy eradicate multifocal glioma in a syngeneic glioblastoma model. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Adenovirus-mediated gene therapy of experimental gliomas. [2013]