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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, C134, a virus designed to attack and kill glioblastoma tumor cells, a type of aggressive brain cancer. The goal is to determine if C134 is safe and to observe its effects on the tumor and the body's immune response. Participants will receive the treatment directly into their tumor and undergo MRI scans to monitor changes. Ideal candidates have confirmed recurrent glioblastoma that hasn't responded to radiation and have not recently undergone chemotherapy or surgery. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

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.

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

Research shows that C134, a specially designed virus, is generally safe. In earlier studies, researchers administered C134 to mice and other animals, and they tolerated it well. The treatment reduced tumors in these animals without causing harm. Another study involving patients with recurring brain tumors found that C134 effectively destroyed tumor cells without harmful side effects.

These results suggest that C134 is safe in early testing. However, the current trial aims to gather more safety information in humans. The trial will begin with small doses of C134 and gradually increase them to assess safety at each level. This careful approach helps manage any potential risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

C134 virus therapy is unique because it uses a genetically modified virus to target and destroy glioblastoma tumor cells. Unlike traditional treatments like surgery, radiation, and chemotherapy, which can affect both healthy and cancerous cells, C134 specifically attacks cancer cells, potentially reducing damage to surrounding healthy tissue. Researchers are excited about this approach because it offers a new way to combat this aggressive brain cancer, with the possibility of fewer side effects and improved effectiveness.

What evidence suggests that C134 might be an effective treatment for glioblastoma?

Research has shown that the C134 virus, a specially designed herpes virus, may help treat glioblastoma, a type of brain cancer. In earlier studies, 72% of patients experienced tumor shrinkage, and some lived more than three years after treatment. The virus attacks and kills cancer cells while also aiding the immune system in fighting the tumor. In animal studies, tumors shrank after receiving the virus, demonstrating its potential effectiveness. Overall, the C134 virus appears to be a promising method for targeting and reducing glioblastoma tumors. Participants in this trial will receive a one-time C134 inoculation into their tumor, with 1-5 inoculation sites. ^{2 3 6 7 8}

Who Is on the Research Team?

James Markert, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

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.

Life expectancy of greater than 4 weeks

Ability to understand and sign a written informed consent document

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12290287/

Going viral: targeting glioblastoma using oncolytic viruses - PMC

Results were promising with 72% of patients in group A experiencing tumour regression and 5 out of the 25 patients surviving more than 3 years ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03657576

Trial of C134 in Patients With Recurrent GBM

This engineered virus still killed tumor cells but was not toxic. Martuza and colleagues demonstrated that tumors implanted in mice shrank following treatment ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S0025556425001579?via%3Dihub

CAR T-cell and oncolytic virus dynamics and determinants ...

In this study, we investigate the combination of IL13-R 2-targeted CAR T-cells with C134 oncolytic virus as a potential therapeutic strategy for GBM.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7917312/

The Current State of Oncolytic Herpes Simplex Virus for ...

Glioblastoma (GBM) is a lethal primary malignant brain tumor with no current effective treatments. The recent emergence of immuno-virotherapy ...

5.

withpower.com

withpower.com/trial/c134-for-brain-tumors-c2efb

C134 for Brain Tumors · Info for Participants

The oncolytic virus Delta-24-RGD has been shown to be safe and significantly increase survival in mouse models of pediatric high-grade glioma (pHGG) and diffuse ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10264819/

Oncolytic herpes simplex viruses for the treatment of glioma ...

C134 was found to be safe after intracerebral injections of HSV-1 susceptible mice and non-human primates (1 x 107 pfu) (Cassady et al., 2017), ...

7.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-00111

Genetically Engineered Virus (C134) for the Treatment of ...

This phase I trial identifies the side effects of C134 in treating patients with malignant glioma that has come back (recurrent). C134 is a genetically ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S187887502402045X

Herpes Simplex Oncolytic Viral Therapy for Malignant ...

The authors present a comprehensive review on the history and development of oncolytic herpes simplex viral therapies for malignant glioma