C134 Virus Therapy for Glioblastoma

(C134-HSV-1 Trial)

Overseen By Natalie Lane, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Must not be taking: Antiviral drugs

Disqualifiers: Chemotherapy, CNS infection, HIV, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 week

19 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this project is to obtain safety information in small groups of individuals, scheduled to receive escalating doses of C134, a cancer killing virus (HSV-1) that has been genetically engineered to safely replicate and kill glioma tumor cells. Safety will be assessed at each dose level before proceeding to the next dose level. A special statistical technique called the Continual Reassessment Method (CRM) will be used to determine when higher doses of virus can be administered. Other objectives of the study include characterization of the activity of C134 after inoculation into the tumor and of the local and systemic immune responses to C134. Patients will also be followed with MRI scans for potential clinical response to C134. The clinical strategy takes advantage of the virus' ability to infect and kill tumor cells while making new virus within the tumors cells; a critical enhancement of this effect is accomplished by the induction of an anti-tumor immune response; both effects are produced by the IRS-1 gene that was placed into the virus by genetic engineering. An additional important component of the research are systematic assessments of the quality of life on treated patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take any drugs active against HSV (like acyclovir) or any other investigational agents. If you're on steroids, your dose should not increase within 2 weeks before the treatment, and it should ideally be equivalent to 2mg of dexamethasone daily.

What data supports the effectiveness of the C134 treatment for glioblastoma?

Research shows that oncolytic viruses, like the C134 treatment, can effectively target and kill glioblastoma cells, reduce tumor growth, and cross the blood-brain barrier. Similar treatments have shown promise in preclinical models, suggesting potential benefits for glioblastoma patients. ^{1 2 3 4 5}

Is C134 Virus Therapy for Glioblastoma safe for humans?

Research on similar treatments, like G207 and G47∆, shows they are generally safe in humans, with some patients experiencing mild side effects like fever and headache. These treatments have been tested in people with glioblastoma, and no severe safety issues were reported. ^{4 6 7 8 9}

How does the C134 treatment differ from other glioblastoma treatments?

C134 is a unique oncolytic virus therapy that specifically targets glioblastoma by using a modified herpes simplex virus to replicate within tumor cells, sparing normal brain cells. It induces a strong immune response and creates long-lasting anti-tumor memory, which is not typically seen with standard treatments. ^{1 2 4 6 10}

Research Team

James Markert, MD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for adults over 18 with recurrent brain tumors (glioblastoma, anaplastic astrocytoma, or gliosarcoma) who've had prior radiation therapy. They must have a life expectancy over 4 weeks and be in good health otherwise. Participants need to use birth control due to unknown effects on fetuses and agree not to join if they're pregnant, have increased their steroid dose recently, or are taking anti-HSV drugs.

Inclusion Criteria

My organ and bone marrow functions are normal.

My diagnosis is a type of aggressive brain tumor.

My previous brain radiotherapy was unsuccessful, and it was over 4 weeks ago.

Exclusion Criteria

My cancer affects areas that need targeted treatment.

I am currently taking medication for herpes.

I do not have any uncontrolled illnesses.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive C134 inoculation into their tumor, with 1-5 inoculation sites

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including MRI scans and immune response assessments

12 months

Multiple visits (in-person and virtual) at day 0, day 1, day 2, day 3, day 7, day 28, month 3, month 6, month 12

Treatment Details

Interventions

• C134

Trial Overview The trial tests C134, a genetically modified herpes virus designed to target and kill tumor cells while boosting the immune response against the tumor. Patients will receive increasing doses of C134 directly into their tumors using MRI guidance. The study also monitors how the body reacts to the virus and any changes in tumor size via MRI scans.

Participant Groups

Group I: C134 Treatment Experimental Treatment 1 Intervention

All patients who enroll will receive C134 inoculation into their tumor (one time procedure with 1-5 inoculation sites)

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+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

Findings from Research

G207, a modified herpes simplex virus, has been shown to be safe for patients with recurrent malignant gliomas when administered in two doses before and after tumor resection, with no severe adverse effects reported.

Preliminary evidence suggests that G207 may have antitumor activity, as indicated by radiographic and neuropathologic findings, and it demonstrated viral replication in the treated areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. Markert, JM., Liechty, PG., Wang, W., et al.[2023]

Despite aggressive treatment options for glioblastoma, including surgery and chemotherapy, the median survival remains low at 14-16 months, highlighting the need for new therapeutic strategies.

Recent data suggest that the Optune™ device, which delivers alternating electrical field therapy, may improve survival in newly diagnosed glioblastoma patients, indicating a promising new approach alongside traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What next for newly diagnosed glioblastoma? Domingo-Musibay, E., Galanis, E.[2022]

C134, a next-generation oncolytic virus, shows improved safety and efficacy in treating malignant gliomas by inducing early interferon signaling that limits replication in non-cancerous cells while effectively targeting tumor cells.

The study demonstrated that C134 elicits a strong T cell-mediated anti-tumor response, leading to improved survival in animal models, and that repeated administration enhances its anti-tumor effects and creates lasting immune memory against the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric HCMV/HSV-1 and Δγ134.5 oncolytic herpes simplex virus elicit immune mediated antigliomal effect and antitumor memory. Ghonime, MG., Jackson, J., Shah, A., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Double Recombinant Vaccinia Virus: A Candidate Drug against Human Glioblastoma. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Vaccinia virus expressing bone morphogenetic protein-4 in novel glioblastoma orthotopic models facilitates enhanced tumor regression and long-term survival. [2021]

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

Clinical trials using oncolytic viral therapy to treat adult glioblastoma: a progress report. [2021]

4. England pubmed.ncbi.nlm.nih.gov

CD137 and PD-L1 targeting with immunovirotherapy induces a potent and durable antitumor immune response in glioblastoma models. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Recent Developments in Glioblastoma Therapy: Oncolytic Viruses and Emerging Future Strategies. [2023]

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

Toxicity and Efficacy of a Novel GADD34-expressing Oncolytic HSV-1 for the Treatment of Experimental Glioblastoma. [2019]

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

Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. [2023]

8. England pubmed.ncbi.nlm.nih.gov

A phase I/II study of triple-mutated oncolytic herpes virus G47∆ in patients with progressive glioblastoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

What next for newly diagnosed glioblastoma? [2022]

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

Chimeric HCMV/HSV-1 and Δγ134.5 oncolytic herpes simplex virus elicit immune mediated antigliomal effect and antitumor memory. [2021]