GlioblastomaPhase 1NCT06614855
A Phase IB 2 Dose Trial of IRS-1 HSV C134 (IND 17296) Administered Intratumorally in Patients With Recurrent Malignant Glioma
A Phase 1 study testing C134 in people with Glioblastoma and Glioblastoma (GBM), run by James Markert, MD 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 administered twice into the brain where the tumor is located. This is a Phase IB 2 dosing study. All the patients who take part in this study will receive the same type of experimental treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Glioblastoma (GBM), Astrocytoma
- What is being tested?
- C134
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jun 2025to 1 Jan 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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, Grade 3 or Grade 4 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 initial C134 administration. Whenever possible, the patient should be on a steroid dose that is equivalent to a dexamethasone dose of ≤ 2mg daily at study entry and initial treatment.
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 unless approved by DSMB). 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 agents (except C134 per protocol).
- Enhancing tumor diameter larger than 5.5 cm for initial treatment or subsequent treatment if only stereotactic biopsy is planned. If resection is planned at the time of second treatment, there is no limit to tumor size at that time. In other words, if the tumor enlarges from less than 5.5 cm to larger than 5.5 cm during the interval between treatment one and two, as long as a resection is planned along with treatment two, no limit in size is present (Note: this size limitation has been derived from experience with prior oHSV therapeutics in malignant glioma).
- 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, occipital lobe, or posterior fossa inoculation or would require access through a ventricle in order to deliver treatment. Additionally, patients with bilateral enhancing tumor are not eligible.
- Prior history of encephalitis, multiple sclerosis. Patient with other active CNS infections are also excluded.
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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 initial 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 that preclude MRI.
- 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
The University of Alabama at Birmingham Hospital
Birmingham, Alabama, 35294
About this study
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 tumor is located. This is a Phase IB 2 dosing study. All the patients who take part in this study will receive the same type of experimental treatment. There is no "placebo" in this study. The patient will receive the dose of C134 administered, which will be added in the tumor infiltrated tissue in the area of the resection cavity. Anywhere from 4-12 patients are expected to take part in the study; the final number will depend on the safety results.
Read the detailed description
This study is divided into the following sections, also called phases: the Initial Screening Phase, Initial Treatment Phase, Initial Treatment Follow-up Phase, 2nd Treatment Screening Phase, 2nd Treatment Phase, 2nd Treatment Follow-up Phase. Before the subject can participate in the study, tests will be performed to make sure that the subject qualifies for the study. This is called the Initial Screening Phase. If the subject qualifies for the study they will then enter the Initial Treatment Phase which is the phase where they will receive the study drug and then enter the Initial Follow-up Phase. If there are signs of progression, the subject will be entered into the 2nd Treatment Phase.
- Conditions
- Glioblastoma, Glioblastoma (GBM), Astrocytoma, Astrocytoma, Grade III, Astrocytoma, Grade IV, Gliosarcoma, Adult
- Being tested
- C134
- Medical subject headings
- Glioblastoma, Astrocytoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C134Drug
Initial Treatment . C134 Dose #1
C134Drug
2nd Treatment. C134 Dose #2
| Study group | Role | What they receive |
|---|---|---|
| Initial Treatment | Experimental | 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. Receives: Drug: C134 |
| 2nd Treatment | Experimental | 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. Receives: Drug: C134 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of a two dose intracerebral injection of C134 virus
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: Enrollment - 12 Month
Secondary outcomes (5)
Time to survival
Patients survival will be recorded (Kaplan-Meier)
Measured: Enrollment - 12 Month
Time to progression
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: Enrollment - 12 Month
Composition of the white blood cells
White blood cell subset analysis by FACS, as a percent of total white blood cell number.
Measured: Enrollment - 12 Month
Measurement of HSV Titer
Detection and quantification of HSV antibody titer via ELISA, pfu/mL.
Measured: Enrollment - 12 Month
Measure interferon levels
Intracellular lymphocyte interferon levels will be assessed by FACS analysis ng/mL
Measured: Enrollment - 12 Month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2024
- Study start2 Jun 2025
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- James Markert, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, James Markert, MD, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06614855
- Sponsor's protocol ID
- IRB-300013560
- Other IDs
- HT94252310805
- Status last verified
- Aug 2026
- First submitted
- 24 Sep 2024
- Last updated
- 13 Aug 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 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB 2 Dose Trial of IRS-1 HSV C134 (IND 17296) Administered Intratumorally in Patients With Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT06614855
- Acronym / sponsor ID
- IRB-300013560
- Conditions
- Glioblastoma, Glioblastoma (GBM), Astrocytoma, Astrocytoma, Grade III, Astrocytoma, Grade IV, Gliosarcoma, Adult
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- James Markert, MDUniversity, hospital or other
- Study start
- 2 Jun 2025 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2028 (estimated)
- First posted
- 26 Sep 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 administered twice into the brain where the tumor is located. This is a Phase IB 2 dosing study. All the patients who take part in this study will receive the same type of experimental treatment. There is no "placebo" in this study. The patient will receive the dose of C134 administered, which will be added in the tumor infiltrated tissue in the area of the resection cavity. Anywhere from 4-12 patients are expected to take part in the study; the final number will depend on the safety results.
Detailed description
This study is divided into the following sections, also called phases: the Initial Screening Phase, Initial Treatment Phase, Initial Treatment Follow-up Phase, 2nd Treatment Screening Phase, 2nd Treatment Phase, 2nd Treatment Follow-up Phase. Before the subject can participate in the study, tests will be performed to make sure that the subject qualifies for the study. This is called the Initial Screening Phase. If the subject qualifies for the study they will then enter the Initial Treatment Phase which is the phase where they will receive the study drug and then enter the Initial Follow-up Phase. If there are signs of progression, the subject will be entered into the 2nd Treatment Phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Initial Treatment | Experimental | Drug: C134Patients 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. |
| 2nd Treatment | Experimental | Drug: C134Before 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 may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients must have histologically or cytologically confirmed recurrent/progressive glioblastoma multiforme, Grade 3 or Grade 4 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 (16 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 unless approved by DSMB). 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 agents (except C134 per protocol).
- Enhancing tumor diameter larger than 5.5 cm for initial treatment or subsequent treatment if only stereotactic biopsy is planned. If resection is planned at the time of second treatment, there is no limit to tumor size at that time. In other words, if the tumor enlarges from less than 5.5 cm to larger than 5.5 cm during the interval between treatment one and two, as long as a resection is planned along with treatment two, no limit in size is present (Note: this size limitation has been derived from experience with prior oHSV therapeutics in malignant glioma).
- 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, occipital lobe, or posterior fossa inoculation or would require access through a ventricle in order to deliver treatment. Additionally, patients with bilateral enhancing tumor are not eligible.
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 |
|---|---|---|
| C134Initial Treatment . C134 Dose #1 | Drug | Initial Treatment |
| C1342nd Treatment. C134 Dose #2 | Drug | 2nd Treatment |
Primary outcome
Safety of a two dose intracerebral injection of C134 virus
Time frame: Enrollment - 12 Month
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
Time to survival
Time frame: Enrollment - 12 Month
Time to progression
Time frame: Enrollment - 12 Month
Composition of the white blood cells
Time frame: Enrollment - 12 Month
Measurement of HSV Titer
Time frame: Enrollment - 12 Month
Measure interferon levels
Time frame: Enrollment - 12 Month
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 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.
The record lists no contact. Use the official record to reach the sponsor.
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 in people with Glioblastoma and Glioblastoma (GBM), run by James Markert, MD 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 17 inclusion and 16 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: under way, not looking for participants, as of the sponsor's last update on 13 Aug 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?
This study is still under way. Results are not available in the source record yet.
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?
Safety of a two dose intracerebral injection of C134 virus (time frame: Enrollment - 12 Month). 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 13 Aug 2026; AzTrials last refreshed its copy on 6 Nov 2026.