Genetically Engineered HSV-1 for Brain Cancer

(M032-HSV-1 Trial)

Overseen By Mary Jane Avant, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Must not be taking: Antivirals, Investigational agents

Disqualifiers: Pregnancy, HIV, CNS infection, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for certain types of brain cancer using a genetically modified version of the Herpes Simplex Virus-1, known as M032 or NSC 733972. The goal is to determine the treatment's safety and optimal dose. It targets individuals with specific brain cancers, such as glioblastoma, who have not responded to standard treatments like radiation and chemotherapy. Eligible participants must have a tumor that cannot be fully removed by surgery and should have completed other treatments at least four weeks prior. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any chemotherapy, cytotoxic therapy, immunotherapy, or investigational agents at least 4 weeks before starting, and 6 weeks for nitrosoureas. You also cannot take any drugs active against HSV (like acyclovir) during the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that M032, a modified version of the Herpes Simplex Virus-1, is being tested for safety in treating brain cancer. Previous studies with similar viruses have shown they can be safe and well-tolerated for brain tumors. These viruses are designed to specifically attack and destroy cancer cells while leaving normal cells unharmed.

In early research, some patients received M032 without major safety issues. Side effects were generally mild and manageable. Since this trial is in an early stage, the main goal is to find the highest safe dose. This phase is crucial for understanding how the treatment works in people and for monitoring any possible side effects.

Overall, while more information is needed, early results suggest that M032 could be a promising and safe option for people with recurrent glioma, a type of brain cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain cancer, such as surgery, radiation, and chemotherapy, M032 is a genetically engineered version of the herpes simplex virus (HSV-1) that's designed to attack cancer cells. This treatment is unique because it uses a virus to target and kill tumor cells directly, potentially sparing healthy cells and reducing side effects. Researchers are excited about M032 because it could offer a more precise and less toxic alternative to traditional therapies, with the potential to improve outcomes for patients with brain cancer.

What evidence suggests that this treatment might be an effective treatment for brain cancer?

Research has shown that M032, a specially modified Herpes Simplex Virus-1, may help treat brain cancer. This virus targets and destroys tumor cells, using them to replicate and continue attacking the cancer. In animal studies, M032 increased the average survival to 188 days in dogs with brain tumors. The trial will administer a single dose of HSV-1 (M032) infused through catheters into the tumor region(s) defined by MRI. This approach suggests that the treatment might extend the lives of people with recurring glioma. Overall, the virus works by killing cancer cells and possibly strengthening the body's immune response against the tumor. ^{1 2 3 4 6}

Who Is on the Research Team?

James Markert, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

Adults over 18 with certain types of brain tumors (glioblastoma, astrocytoma, gliosarcoma) that have recurred. They must have tried radiotherapy and chemotherapy already, be in good health otherwise, not pregnant or breastfeeding, willing to use contraception and avoid contact with vulnerable individuals post-treatment. Tumors should be a specific size and location for local treatment.

Inclusion Criteria

Agreement to use adequate contraception, avoid intimate contact with certain individuals, and refrain from blood donation during the trial

Ability to understand and sign a written informed consent document

I am a woman who can have children and I have a negative pregnancy test from the last 14 days.

Exclusion Criteria

I haven't had chemotherapy, immunotherapy, or surgery in the last 4 weeks.

I have a history of certain brain or nerve conditions.

I haven't needed more steroids, don't have an active oral herpes lesion, and am not on drugs for HSV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of HSV-1 (M032) infused through catheters into the tumor region

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• M032 (NSC 733972)

Trial Overview The trial is testing M032 (NSC 733972), a genetically engineered Herpes Simplex Virus-1 designed to treat recurrent malignant gliomas. It's given directly into the tumor site to see if it's safe at its highest dose and how well patients tolerate it.

How Is the Trial Designed?

Group I: Group A single dose of HSV-1 (M032) Experimental Treatment 1 Intervention

single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Genetically engineered herpes simplex viruses, particularly the R4009 mutant, have shown promising results in treating malignant gliomas, significantly prolonging survival in a mouse model and even eradicating tumors in some cases.

The study highlights the potential of using oncolytic viruses, like R4009 and other gamma (1)34.5 mutants, as a novel therapeutic approach for primary brain tumors, demonstrating both efficacy in tumor reduction and the possibility of long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors. Andreansky, SS., He, B., Gillespie, GY., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4932657/

Design of a Phase I Clinical Trial to Evaluate M032, a ... This clinical protocol outlines the dose-escalating phase I study for evaluation of M032 in patients with recurrent or progressive malignant glioma.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02062827

Genetically Engineered HSV-1 Phase 1 Study for the ... Replication of M032 in the tumor itself not only kills the infected tumor cells, but causes the tumor cell to act as a factory to produce new virus. These virus ...

3. frontiersin.org frontiersin.org/journals/surgery/articles/10.3389/fsurg.2020.00059/full

Design of a Phase I Clinical Trial to Evaluate M032, ... A phase I clinical trial to evaluate M032, a genetically engineered HSV-1 expressing IL-12, in combination with a checkpoint inhibitor in canine patients with ...

4. aacrjournals.org aacrjournals.org/cancerres/article/80/16_Supplement/4568/643325/Abstract-4568-The-One-Health-Consortium-and

evaluating M032, a genetically engineered HSV-1 expressing ... Results: Preliminary data from Stage 1 have demonstrated a median survival of 188 days among all canines following infusion of M032 HSV (95 ...

5. cell.com cell.com/molecular-therapy-family/oncology/fulltext/S2950-3299(24)00041-9

Enhanced therapeutic efficacy for glioblastoma ... Design of a Phase I Clinical Trial to Evaluate M032, a Genetically Engineered HSV-1 Expressing IL-12, in Patients with Recurrent/Progressive ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/27/NCT02062827/Prot_SAP_ICF_000.pdf

Phase 1 Study of M032 (NSC 733972), a Genetically ... The efficacy of herpes simplex virus (HSV) as a treatment for brain tumors has been demonstrated experimentally. The earliest studies used a ...