Recurrent Malignant GliomaPhase 1NCT06193174
Re-Administration of C134 in Patients With Recurrent GBM (C134-HSV-1)
A Phase 1 study testing C134 Re-Administration in people with Recurrent Malignant Glioma and Glioblastoma Multiforme of Brain, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Malignant Glioma, Glioblastoma Multiforme of Brain, Gliosarcoma of Brain
- What is being tested?
- C134 Re-Administration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jun 2024to 7 Mar 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
Official title: A Phase IB (Repeat Dosing) Trial of Second Dose Oncolytic HSV Administered Intratumorally in Patients With Recurrent Malignant Glioma.
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.
Read the detailed description
C134 is a genetically engineered herpes simplex virus or "HSV" (the virus that usually causes cold sores and rarely, a severe infection of the brain). It has been known that viruses may kill tumor cells. When tumor cells are mixed with certain viruses in the laboratory, the tumor cells die. The DNA of the (HSV) virus has been modified so that tumor cells may be killed when infected by C134. The changes made to the virus (HSV) should help prevent the (C134) virus from infecting normal brain tissue. Extensive testing in both mice and monkeys has demonstrated that C134 is not able to cause HSV when injected directly into the brain. C134 may also be able to help kill tumor cells because it can prevent tumor cells from killing it more effectively than other, similar viruses can. This allows it to infect and kill more brain tumor cells. C134 has been tested in more than ten patients previously. The virus has had only two instances of known significant toxicities. In one patients with extensive disease present on both sides of the brain, the virus traveled throughout the brain and as a result, caused extensive inflammation that required treatment with an antiviral drug. The patient recovered partially, but eventually succumbed to their tumor. A second patient developed an infection of the retina (back of the eye) apparently as a result of the virus migrating to that area from the site of inoculation in the occipital lobe.
Based on these findings the investigators have amended the protocol to protect future patients from these toxicities as follows: 1) The dose of the virus being administered has been lowered; 2) patients with enhancing tumor on both sides of the brain are not eligible for the trial and 3) patients with disease in the occipital lobe which has connections to the retina are not eligible for the trial
Based on laboratory testing, the investigators believe multiple doses of C134 viral therapy in cases such as the patients, could potentially benefit from repeat treatment as this has been seen in preclinical studies, since the patients have received C134, the patients are thus eligible for retreatment under this protocol.
- Conditions
- Recurrent Malignant Glioma, Glioblastoma Multiforme of Brain, Gliosarcoma of Brain, Anaplastic Astrocytoma of Brain
- Being tested
- C134 Re-Administration
- Keywords
- Brain Tumor, Progressive, Recurrent
- Medical subject headings
- Glioma, Brain Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C134 Re-AdministrationDrug
Also called C134-HSV-1 Re-Administration
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).
| Study group | Role | What they receive |
|---|---|---|
| Recurrent Malignant Glioma | Experimental | Participants that have completed the study "Trial of C134 in Patients With Recurrent GBM (C134-HSV-1)" Receives: Drug: C134 Re-Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline through month 12
Secondary outcomes (5)
Measure of Progression Free Survival
Patients will receive contrast-enhanced MRI to monitor progression (changes in tumor volume or tumor enhancement assessed by the iRANO criteria). As indicated in the criteria, biopsy and/or resection may be performed in instances of uncertainty. Determination of time to progression (in months) will be recorded for each patient and median progression-free survival will be calculated for the entire cohort (Kaplan-Meier).
Measured: pre-study, day 3, day 28, month 3, month 6, month 12
Measure Overall Survival
Patients survival will be recorded (Kaplan-Meier)
Measured: day 0, day 1, day 2, day 3, day 7, day 28, month 3, month 6, month 12
Measurement of HSV titer
Detection and quantification of HSV antibody titer via ELISA, pfu/mL.
Measured: pre-study, day 28, month 3, month 6, month 12
Composition of the white blood cells
White blood cell subset analysis by FACS, as a percent of total white blood cell number.
Measured: pre-study, day 2, day 7, day 28, month 3, month 6, month 12
Measure interferon levels
Intracellular lymphocyte interferon levels will be assessed by FACS analysis ng/mL
Measured: pre-study, day 2, day 7, day 28, month 3, month 6, month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2024
- Study start21 Jun 2024
- Primary completion7 Mar 2025
- Study completion7 Mar 2025
Why it stopped: Not enough eligible participants to enroll.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Malignant GliomaStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James Markert, MD, University of Alabama at Birmingham
- Investigators
- James Markert, MD, Principal investigator, The University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06193174
- Sponsor's protocol ID
- IRB-300012182
- Other IDs
- HT9425-23-1-0805
- Status last verified
- Jan 2026
- First submitted
- 28 Nov 2023
- Last updated
- 22 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB (Repeat Dosing) Trial of Second Dose Oncolytic HSV Administered Intratumorally in Patients With Recurrent Malignant Glioma.
- ClinicalTrials.gov ID
- NCT06193174
- Acronym / sponsor ID
- IRB-300012182
- Conditions
- Recurrent Malignant Glioma, Glioblastoma Multiforme of Brain, Gliosarcoma of Brain, Anaplastic Astrocytoma of Brain
- Keywords
- Brain Tumor, Progressive, Recurrent
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Not enough eligible participants to enroll.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 21 Jun 2024 (actual)
- Primary completion
- 7 Mar 2025 (actual)
- Study completion
- 7 Mar 2025 (actual)
- First posted
- 5 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
C134 is a genetically engineered herpes simplex virus or "HSV" (the virus that usually causes cold sores and rarely, a severe infection of the brain). It has been known that viruses may kill tumor cells. When tumor cells are mixed with certain viruses in the laboratory, the tumor cells die. The DNA of the (HSV) virus has been modified so that tumor cells may be killed when infected by C134. The changes made to the virus (HSV) should help prevent the (C134) virus from infecting normal brain tissue. Extensive testing in both mice and monkeys has demonstrated that C134 is not able to cause HSV when injected directly into the brain. C134 may also be able to help kill tumor cells because it can prevent tumor cells from killing it more effectively than other, similar viruses can. This allows it to infect and kill more brain tumor cells. C134 has been tested in more than ten patients previously. The virus has had only two instances of known significant toxicities. In one patients with extensive disease present on both sides of the brain, the virus traveled throughout the brain and as a result, caused extensive inflammation that required treatment with an antiviral drug. The patient recovered partially, but eventually succumbed to their tumor. A second patient developed an infection of the retina (back of the eye) apparently as a result of the virus migrating to that area from the site of inoculation in the occipital lobe.
Based on these findings the investigators have amended the protocol to protect future patients from these toxicities as follows: 1) The dose of the virus being administered has been lowered; 2) patients with enhancing tumor on both sides of the brain are not eligible for the trial and 3) patients with disease in the occipital lobe which has connections to the retina are not eligible for the trial
Based on laboratory testing, the investigators believe multiple doses of C134 viral therapy in cases such as the patients, could potentially benefit from repeat treatment as this has been seen in preclinical studies, since the patients have received C134, the patients are thus eligible for retreatment under this protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Recurrent Malignant Glioma | Experimental | Drug: C134 Re-AdministrationParticipants that have completed the study "Trial of C134 in Patients With Recurrent GBM (C134-HSV-1)" |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| C134 Re-AdministrationAlso: C134-HSV-1 Re-AdministrationAdministration of a second dose of C134 to participants that have completed the study Trial of C134 in Patients With Recurrent GBM (C134-HSV-1). | Drug | Recurrent Malignant Glioma |
Primary outcome
Measure of Treatment-Emergent Adverse Events
Time frame: baseline through month 12
Adverse events will be monitored and any changes in status will be recorded for each patient as outlined in CTCAE v4.0 reporting requirements.
5 secondary outcomes
Measure of Progression Free Survival
Time frame: pre-study, day 3, day 28, month 3, month 6, month 12
Measure Overall Survival
Time frame: day 0, day 1, day 2, day 3, day 7, day 28, month 3, month 6, month 12
Measurement of HSV titer
Time frame: pre-study, day 28, month 3, month 6, month 12
Composition of the white blood cells
Time frame: pre-study, day 2, day 7, day 28, month 3, month 6, month 12
Measure interferon levels
Time frame: pre-study, day 2, day 7, day 28, month 3, month 6, month 12
Results and safety
The study was stopped early (reason given: Not enough eligible participants to enroll.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Markert, MD principal investigator
The University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing C134 Re-Administration in people with Recurrent Malignant Glioma and Glioblastoma Multiforme of Brain, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Not enough eligible participants to enroll.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure of Treatment-Emergent Adverse Events (time frame: baseline through month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2026.