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

29 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment M032 for brain cancer?

Research shows that genetically engineered herpes simplex viruses, like M032, have been effective in killing brain tumor cells in lab studies and animal models. These viruses are designed to target and destroy cancer cells while being safe for normal brain cells, making them a promising treatment for brain cancer. ^{1 2 3 4 5}

Is the genetically engineered HSV-1 treatment M032 safe for humans?

Research on M032, a genetically engineered herpes simplex virus, shows it is generally safe in nonhuman primates, with only mild and temporary inflammation observed. Elevated white blood cell counts were noted shortly after administration, but no significant long-term adverse effects were found. ^{1 4 5 6 7}

What makes the treatment M032 (NSC 733972) unique for brain cancer?

M032 is a genetically engineered herpes simplex virus (HSV-1) designed to selectively target and kill brain tumor cells while sparing normal brain cells. This treatment is unique because it uses a virus that has been modified to be safe for the brain and can directly destroy cancer cells, potentially offering a new approach compared to traditional therapies like surgery, radiation, or chemotherapy. ^{1 2 5 8 9}

What is the purpose of this trial?

To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simplex Virus-1 in patients who would not be eligible for surgical resection of recurrent glioma To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simples Virus-1 in patients who would benefit from surgical resection of recurrent glioma

Research Team

James Markert, MD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Therapy of experimental human brain tumors using a neuroattenuated herpes simplex virus mutant. [2023]

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

Evaluation of genetically engineered herpes simplex viruses as oncolytic agents for human malignant brain tumors. [2022]

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

The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors. [2022]

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

Evaluation of the safety and biodistribution of M032, an attenuated herpes simplex virus type 1 expressing hIL-12, after intracerebral administration to aotus nonhuman primates. [2021]

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

Comparison of genetically engineered herpes simplex viruses for the treatment of brain tumors in a scid mouse model of human malignant glioma. [2023]

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

Engineered herpes simplex virus expressing bacterial cytosine deaminase for experimental therapy of brain tumors. [2019]

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

Preclinical evaluation of a genetically engineered herpes simplex virus expressing interleukin-12. [2023]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Herpesvirus vectors for therapy of brain tumors. [2021]

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

"Armed" oncolytic herpes simplex viruses for brain tumor therapy. [2021]