Re-Administration of C134 in Patients With Recurrent GBM (C134-HSV-1)

NCT06193174 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: IRB-300012182HT9425-23-1-0805
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine how safe and how well-tolerated the experimental study drug, C134 is when re-administered into the brain where the tumor is located.

Conditions

Recurrent Malignant Glioma; Glioblastoma Multiforme of Brain; Gliosarcoma of Brain; Anaplastic Astrocytoma of Brain

Keywords

Brain Tumor; Progressive; Recurrent

Outcome Measures

Primary Outcomes (1)

• Measure of Treatment-Emergent Adverse Events

  Adverse events will be monitored and any changes in status will be recorded for each patient as outlined in CTCAE v4.0 reporting requirements.

  baseline through month 12

Secondary Outcomes (5)

• Measure of Progression Free Survival

  pre-study, day 3, day 28, month 3, month 6, month 12

• Measure Overall Survival

  day 0, day 1, day 2, day 3, day 7, day 28, month 3, month 6, month 12

• Measurement of HSV titer

  pre-study, day 28, month 3, month 6, month 12

• Composition of the white blood cells

  pre-study, day 2, day 7, day 28, month 3, month 6, month 12

• Measure interferon levels

  pre-study, day 2, day 7, day 28, month 3, month 6, month 12

Study Arms (1)

Recurrent Malignant Glioma

EXPERIMENTAL

Participants that have completed the study "Trial of C134 in Patients With Recurrent GBM (C134-HSV-1)"

Drug: C134 Re-Administration

Interventions

C134 Re-Administration DRUG

Administration of a second dose of C134 to participants that have completed the study Trial of C134 in Patients With Recurrent GBM (C134-HSV-1).

Also known as: C134-HSV-1 Re-Administration

Recurrent Malignant Glioma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed recurrent/progressive glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma.
• Prior therapy. Patients must have failed a course of external beam radiotherapy to the brain at least 4 weeks prior to enrollment.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of C134 in patients \<18 years of age, children are excluded from this study but will be eligible for future pediatric phase 1 single-agent trials.
• Karnofsky Performance Status ≥70%
• Life expectancy of greater than 4 weeks.
• Patients must have normal organ and marrow function as defined below:
• leukocytes \>3,000/ μl absolute neutrophil count \>1,500/ μl platelets \>100,000/ μl total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal Creatinine within normal institutional limits OR creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
• Residual lesion must be ≥1.0 cm in diameter as determined by MRI.
• The effects of C134 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the first six months after receiving C134. Because it is currently unknown if C134 can be transmitted by sexual contact, a barrier method of birth control should be employed. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.
• Females of childbearing potential must not be pregnant; this will be confirmed by a negative serum pregnancy test within 14 days prior to starting study treatment.
• Steroid use is allowed as long as dose has not increased within 2 weeks of scheduled C134 administration whenever possible, the patient should be on a steroid dose that is equivalent to a dexamethasone dose of ≤ 4mg daily at the time of treatment.
• Patients must have previously been treated with C134 in the Phase I dose escalation study here at UAB \> 4 weeks prior and have shown evidence of either tumor progression or pseudoprogression by MRI.

You may not qualify if:

• Patients who have had chemotherapy, cytotoxic therapy, immunotherapy or gene therapy within 6 weeks prior to entering the study, surgical resection within 4 weeks prior to entering the study, or have received experimental viral therapy at any time (e.g., adenovirus, retrovirus or herpesvirus\* protocol). Also, those who have not recovered from adverse events due to therapeutic interventions administered more than 4 weeks earlier.
• Patients may not be receiving any other investigational therapeutic agents
• Enhancing tumor diameter larger than 5.5 cm
• History of allergic reactions or CTCAE version 5.0 Grade IV toxicity attributed to C134 or compounds of similar biologic composition to C134.
• Tumor involvement which would require ventricular, brainstem, basal ganglia, or posterior fossa inoculation or would require access through a ventricle in order to deliver treatment.
• Prior history of encephalitis, multiple sclerosis, or other CNS infection.
• Active oral herpes lesion.
• Concurrent therapy with any drug active against HSV (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir).
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other medical condition that precludes surgery. Also, psychiatric illness/social situations that would limit compliance with study requirements.
• Required steroid increase within 2 weeks of scheduled C134 administration. When possible, the patient should be on a dexamethasone equivalent dose of ≤ 2mg daily at the time of treatment.
• Known history of allergic reaction to IV contrast material that is not amenable to pre-treatment by UAB protocol.
• Have a pacemaker, ferro-magnetic aneurysm clips, metal infusion pumps, metal or shrapnel fragments, or certain types of stents.
• Received Bevacizumab (Avastin) therapy within 4 weeks of scheduled C134 administration.
• Excluded patient groups Pregnant women are excluded from this study because C134 is a viral oncolytic therapy with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with C134 breastfeeding should be discontinued if the mother is treated with C134.
• Immune deficient, because patients with immune deficiency will be unable to mount the anticipated immune response underlying this therapeutic rationale, HIV-seropositive patients are excluded from this study. Other treatment studies for this disease that are less dependent on the patients' immune response are more appropriate for HIV-seropositive patients.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Glioma; Brain Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• James Markert, MD

  The University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair, Department of Neurosurgery

Study Record Dates

• First Submitted: November 28, 2023
• First Posted: January 5, 2024
• Study Start: June 21, 2024
• Primary Completion: March 7, 2025
• Study Completion: March 7, 2025
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)