C134 for Brain Tumors

Overseen By James Markert, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: James Markert, MD

Must not be taking: Antivirals, others

Disqualifiers: Chemotherapy, Immunotherapy, CNS infections, others

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

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerance of a new experimental drug, C134, for treating certain types of brain tumors. All participants will receive the C134 treatment, administered directly to the tumor area in the brain. The trial aims to assess patient tolerance without using a placebo. It is suitable for individuals with specific brain tumors, such as recurrent glioblastoma, who have previously undergone radiation but still have a tumor. Participants must have a tumor at least 1 cm in diameter and should not have had recent chemotherapy or certain other treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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 (a type of virus) or any other investigational agents. If you're on steroids, your dose should not increase within 2 weeks before starting the trial, and it should ideally be equivalent to 2mg of dexamethasone daily.

Is there any evidence suggesting that the treatment C134 is likely to be safe for humans?

Research has shown that the investigational drug C134 appears to be safe. Animal studies tested C134 and found it safe, even in sensitive areas like the brain that are prone to infection. These tests help researchers predict how the treatment might work in humans.

In another study, researchers administered different doses of C134 to humans, focusing on safety. They aimed to assess how well people could tolerate the treatment, especially when delivered directly into brain tissue.

This is an early phase trial, one of the first steps to check the treatment's safety in humans. Early phase trials usually involve a small number of participants, allowing for close monitoring to ensure safety. This stage is crucial for identifying any potential side effects and ensuring the treatment does not cause harm. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain tumors?

Unlike the standard treatments for brain tumors, such as surgery, radiation, and chemotherapy, IRS-1 HSV C134 introduces a novel approach by utilizing a genetically modified virus. This virus is designed to specifically target and destroy tumor cells, sparing healthy brain tissue. Researchers are excited because this targeted method could potentially reduce side effects and improve precision in attacking the tumor, offering a fresh hope for better outcomes in brain tumor treatment. Additionally, the localized delivery method via stereotactic biopsy allows for direct application to the tumor, potentially enhancing the effectiveness of the treatment.

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

Research has shown that IRS-1 HSV C134, the investigational treatment in this trial, uses a modified virus to attack brain tumors. In earlier studies, tumors in mice shrank after treatment with this type of virus. Another study found that a similar virus not only reduced tumor size but also extended the lifespan of mice. This method is part of a new research area that uses viruses to target and destroy cancer cells while sparing healthy cells. Early results suggest that IRS-1 HSV C134 could be a promising treatment for brain tumors, but further research is needed to confirm its effectiveness in humans. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for a small group of 4-12 patients with recurrent malignant glioma, which includes specific brain tumors like glioblastoma and astrocytoma. Participants must have a tumor that can be reached to administer the treatment directly.

Inclusion Criteria

Residual lesion must be ≥1.0 cm in diameter as determined by MRI

Patients must agree to use adequate contraception

My diagnosis is a type of aggressive brain tumor.

Exclusion Criteria

My tumor is larger than 5.5 cm.

I have had a condition where my lymphocytes grow abnormally.

I currently have an active cold sore.

Timeline for a Trial Participant

Initial Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive the first dose of the study drug C134 administered intratumorally

1 week

1 visit (in-person)

Initial Treatment Follow-up

Participants are monitored for safety and effectiveness after the initial treatment

4 weeks

2 visits (in-person)

2nd Treatment Screening

Participants are assessed for eligibility for the second dose of treatment

2 weeks

2nd Treatment

Participants receive the second dose of the study drug C134 if eligible

1 week

1 visit (in-person)

2nd Treatment Follow-up

Participants are monitored for safety and effectiveness after the second treatment

4 weeks

2 visits (in-person)

Long-term Follow-up

Participants are monitored for long-term safety and survival outcomes

12 months

What Are the Treatments Tested in This Trial?

Interventions

• IRS-1 HSV C134

Trial Overview The study is testing the safety and tolerability of an experimental drug called C134 when injected twice into the brain tissue where the tumor is located. There's no placebo; all participants receive the actual drug in their tumor infiltrated tissue.

How Is the Trial Designed?

Group I: Initial Treatment Experimental Treatment 1 Intervention

Patients will undergo a contrasted MRI scan to determine the site for stereotactic biopsy. For dose #1, patients will be treated under monitored local anesthesia, or at the surgeon's discretion, under general anesthesia. Patients will then undergo stereotactic biopsy of their tumor. While evidence of radiation damage or necrosis may be present on the frozen section, inoculation with C134 will only proceed if viable, recurrent glioma is also present on the frozen section. The dose level of C134 will be 1 x 105 plaque forming units (pfu). Virus will be inoculated via catheters placed stereotactically in enhancing regions of tumor or immediately adjacent in non-enhancing tumor infiltrated regions at up to 5 different loci (each injection over 2 minutes). Catheters will be removed directly after administration for treatment 1.

Group II: 2nd Treatment Experimental Treatment 1 Intervention

Before dose #2 administration, patients will undergo preoperative assessment of their disease status. If they are deemed to have had a complete response (CR), no treatment will be undertaken until there is evidence of a possible recurrence. If this does not occur until after week 16, the patient's situation will be discussed with the DSMB and a decision made about possible second treatment. If the patient has had a partial response or stable disease, and their tumor remains less than 5.5 cm in size, they wil lbe treated with stereotactic biopsy using the same technique described for dose #1 If the patient has suffered progression or peudoprogression, or if in the estimation of the surgeon it is not safe to perform inoculation alone, they will undergo craniotomy for resection of the tumor.

Who Is Running the Clinical Trial?

James Markert, MD

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

G207, a genetically engineered herpes simplex virus, was found to be non-toxic when administered to the cerebellum of mice, showing no harmful effects on brain or organ health after 7 and 30 days.

The treatment with G207 significantly increased survival rates in mice with aggressive MYC-overexpressed group 3 medulloblastoma, suggesting its potential as an effective therapy for children with difficult-to-treat cerebellar tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of oncolytic HSV-1 G207 inoculated into the cerebellum of mice. Bernstock, JD., Vicario, N., Li, R., et al.[2021]

A Phase 1 clinical trial is being conducted to evaluate the safety and tolerability of the oncolytic herpes simplex virus G207 combined with low-dose radiation in treating recurrent malignant pediatric cerebellar tumors, which are challenging to treat and often lead to poor outcomes.

The trial aims to not only assess safety but also to gather data on the efficacy of this treatment approach by monitoring tumor response, survival rates, and quality of life, potentially paving the way for more effective and less harmful therapies for children with brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and Rationale for First-in-Human Phase 1 Immunovirotherapy Clinical Trial of Oncolytic HSV G207 to Treat Malignant Pediatric Cerebellar Brain Tumors. Bernstock, JD., Bag, AK., Fiveash, J., et al.[2021]

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 intrinsic pontine gliomas (DIPGs), indicating its potential as a treatment option.

The therapeutic effect of Delta-24-RGD is attributed to both its ability to directly kill tumor cells and to stimulate an immune response against the tumors, leading to the initiation of a phase I/II clinical trial for newly diagnosed DIPG patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models. Martínez-Vélez, N., Garcia-Moure, M., Marigil, M., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03657576

Study Details | NCT03657576 | Trial of C134 in Patients ... Martuza and colleagues demonstrated that tumors implanted in mice shrank following treatment with varying doses of this virus. Additional modified viruses based ...

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

The Current State of Oncolytic Herpes Simplex Virus for ... OHSVULBP3 inhibited tumor growth and prolonged median survival (18 days) compared to unarmed oHSV (8 days).

3. trials.braintumor.org trials.braintumor.org/trials/NCT06614855

A Phase IB 2 Dose Trial of IRS-1 HSV C134 (IND 17296 ... The purpose of this study is to determine how safe and how well-tolerated the experimental study drug, C134 is when administered twice into the brain where the ...

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

C134 for Brain Tumors · Info for Participants What data supports the effectiveness of the treatment IRS-1 HSV C134 for brain tumors? Research on similar treatments, like the oncolytic herpes simplex virus ...

5. 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

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5363760/

Pre-clinical Assessment of C134, a Chimeric Oncolytic ... Here we present data demonstrating the safety of C134, a chimeric oHSV construct, in CBA mice as well as in a limited number of the HSV-sensitive non-human ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1936523317303510

Chimeric HCMV/HSV-1 and Δγ134.5 oncolytic herpes ... It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells. We sought to identify how C134 ...

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/76/NCT03657576/Prot_SAP_ICF_000.pdf

A Phase I Trial of IRS-1 HSV C134 (IND 17296) ... HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: safety data and long-term survival.