Recurrent Glioblastoma MultiformePhase 1M032-HSV-1NCT02062827
Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma
A Phase 1 study testing M032 (NSC 733972) in people with Recurrent Glioblastoma Multiforme and Progressive Glioblastoma Multiforme, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simplex Virus-1 in patients who would not be eligible for surgical resection of recurrent glioma To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simples Virus-1 in patients who… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Glioblastoma Multiforme, Progressive Glioblastoma Multiforme, Anaplastic Astrocytoma or Gliosarcoma
- What is being tested?
- M032 (NSC 733972)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Nov 2013to Sep 2027
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma.
- Prior therapy: Patients must have failed external beam radiotherapy to the brain, and if eligible and tolerated, undergone appropriate treatment with temozolomide chemotherapy. All radiation and additional chemotherapies must have been completed at least 4 weeks prior to enrollment. Prior therapy with nitrosoureas must have been completed at least 6 weeks prior to enrollment.
- Age ≥18 years (age of majority for clinical trials in Alabama). Because no dosing or adverse event data are currently available on the use of M032 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)(aspartate aminotransferase)/ALT(SGPT)(alanine aminotransferase): <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 and < 5.5 cm in diameter without bilateral extension through the corpus callosum as determined by MRI as this is a locally delivered treatment. These parameters will be re-evaluated on imaging done on the day of catheter implantation and if the lesion no longer meets.
- The effects of M032 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 M032. Because it is currently unknown if M032 can be transmitted by sexual contact, a barrier method of birth control must be employed and for six (6) months following the administration of the study drug. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. For two weeks after receiving M032, subjects should avoid intimate contact with pregnant women, infants and young children and individuals with decreased immunity (ability to fight infection). Subjects should also refrain from donating blood during the trial
- 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 M032 administration. Whenever possible, the patient should be on a steroid dose that is equivalent to a dexamethasone dose of ≤ 2mg daily at the time of treatment.
Who cannot join
- Patients who have had chemotherapy, cytotoxic therapy, immunotherapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas), surgical resection within 4 weeks prior to entering the study, or have received experimental viral therapy or gene therapy at any time (e.g., adenovirus, retrovirus or herpes virus protocol). However, this does not preclude re-treatment with M032 at a later date.
- Patients 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.
- History of allergic reactions attributed to compounds of similar biologic composition to M032 or to IL-12.
- 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. Also, since M032 is a local treatment, patients whose tumors have bilateral extension through the corpus callosum, those with actively growing multifocal disease by MRI, and/or CSF dissemination/ leptomeningeal disease, are ineligible.
- Prior history of encephalitis, multiple sclerosis, or other CNS infection.
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- Required steroid increase within 2 weeks of scheduled M032 administration. When possible, the patient should be on a dexamethasone equivalent dose of ≤ 2mg daily at the time of treatment.
- Active oral herpes lesion.
- Concurrent therapy with any drug active against HSV (acyclovir, valacyclovir, penciclovir, famciclovir, gancyclovir, 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.
- Excluded patient groups
- Pregnant women are excluded from this study because M032 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 M032, breastfeeding women will not be included in the study.
- 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.
- Patients with known history of allergic reaction to IV contrast material that is not amenable to pre-treatment by University of Alabama at Birmingham protocol.
- Patients with pacemakers, ferro-magnetic aneurysm clips, metal infusion pumps, metal or shrapnel fragments or certain types of stents.
- Receipt of Gliadel Therapy.
- (Receipt of Bevacizumab (Avastin) therapy within 4 weeks of scheduled M032 administration. (Receipt of Bevacizumab (Avastin) greater than 4 weeks of scheduled M032 administration does not exclude patient.)
- Any other reason the investigator deems subject is unfit for participation in the study.
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 1 Study of M032 (NSC 733972), a Genetically Engineered HSV-1 Expressing IL-12, in Patients With Recurrent/Progressive Glioblastoma Multiforme, Anaplastic Astrocytoma, or Gliosarcoma
To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simplex Virus-1 in patients who would not be eligible for surgical resection of recurrent glioma To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simples Virus-1 in patients who would benefit from surgical resection of recurrent glioma
Read the detailed description
M032 is a second-generation oncolytic herpes simplex virus (oHSV) that is conditionally replication competent; that is, similar to G207, a first generation oHSV, it can replicate in tumor cells, but not in normal cells, thus killing the tumor cells directly through this process. Replication of M032 in the tumor itself not only kills the infected tumor cells, but causes the tumor cell to act as a factory to produce new virus. These virus particles are released as the tumor cell dies, and can then proceed to infect other tumor cells in the vicinity, and continue the process of tumor kill. In addition to this direct oncolytic activity, the virus carries a therapeutic payload--acting as a gene therapy vector, too--and causes the tumor cell to synthesize and secrete an immunity-stimulating protein called Interleukin-12 (IL-12) before it is killed. This IL-12 is released and promotes an immune response against surviving tumor cells, which increases the antitumor effect of the therapy. The IL-12 that is expressed can also produce an anti-angiogenic effect, by interfering with the production of new tumor blood vessels necessary to allow tumor growth. Anti-angiogenic therapies potentially starve the tumor of necessary oxygen and nutrients. Thus, the M032 oHSV produces three different potential mechanisms for antitumor effects. The virus has also been genetically-engineered to minimize the production of any toxic effects for the patient receiving the therapy.
- Conditions
- Recurrent Glioblastoma Multiforme, Progressive Glioblastoma Multiforme, Anaplastic Astrocytoma or Gliosarcoma
- Being tested
- M032 (NSC 733972)
- Keywords
- Glioma, Virus, Oncolytic virus, Gene therapy, Immunotherapy, Brain Tumors
- Medical subject headings
- Glioblastoma, Astrocytoma, Gliosarcoma, Glioma, Virus Diseases, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
M032 (NSC 733972)Biological
A single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI
| Study group | Role | What they receive |
|---|---|---|
| Group A single dose of HSV-1 (M032) | Experimental | single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI Receives: Biological: M032 (NSC 733972) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of M032
Measured: baseline to12 months
Secondary outcomes (3)
Time to Progression Assessment
Measured: baseline to 12 months
The Time of Survival Assessment
Measured: baseline to 12 months
The Time of Biologic Assessment
Measured: baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2014 (estimated)
- Study start25 Nov 2013
- Primary completionSep 2022
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Glioblastoma MultiformeStudies 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
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, James Markert, MD, University of Alabama at Birmingham
- Investigators
- James M. Markert, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02062827
- Sponsor's protocol ID
- UAB-1317
- Other IDs
- R01CA217179
- Acronym
- M032-HSV-1
- Status last verified
- Sep 2025
- First submitted
- 9 Feb 2014
- Last updated
- 2 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of M032 (NSC 733972), a Genetically Engineered HSV-1 Expressing IL-12, in Patients With Recurrent/Progressive Glioblastoma Multiforme, Anaplastic Astrocytoma, or Gliosarcoma
- ClinicalTrials.gov ID
- NCT02062827
- Acronym / sponsor ID
- M032-HSV-1 / UAB-1317
- Conditions
- Recurrent Glioblastoma Multiforme, Progressive Glioblastoma Multiforme, Anaplastic Astrocytoma or Gliosarcoma
- Keywords
- Glioma, Virus, Oncolytic virus, Gene therapy, Immunotherapy, Brain Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 25 Nov 2013 (actual)
- Primary completion
- Sep 2022 (actual)
- Study completion
- Sep 2027 (estimated)
- First posted
- 14 Feb 2014 (estimated)
- Results
- Posted 2 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simplex Virus-1 in patients who would not be eligible for surgical resection of recurrent glioma To determine the safety and tolerability of the maximum dose for laboratory engineered Herpes Simples Virus-1 in patients who would benefit from surgical resection of recurrent glioma
Detailed description
M032 is a second-generation oncolytic herpes simplex virus (oHSV) that is conditionally replication competent; that is, similar to G207, a first generation oHSV, it can replicate in tumor cells, but not in normal cells, thus killing the tumor cells directly through this process. Replication of M032 in the tumor itself not only kills the infected tumor cells, but causes the tumor cell to act as a factory to produce new virus. These virus particles are released as the tumor cell dies, and can then proceed to infect other tumor cells in the vicinity, and continue the process of tumor kill. In addition to this direct oncolytic activity, the virus carries a therapeutic payload--acting as a gene therapy vector, too--and causes the tumor cell to synthesize and secrete an immunity-stimulating protein called Interleukin-12 (IL-12) before it is killed. This IL-12 is released and promotes an immune response against surviving tumor cells, which increases the antitumor effect of the therapy. The IL-12 that is expressed can also produce an anti-angiogenic effect, by interfering with the production of new tumor blood vessels necessary to allow tumor growth. Anti-angiogenic therapies potentially starve the tumor of necessary oxygen and nutrients. Thus, the M032 oHSV produces three different potential mechanisms for antitumor effects. The virus has also been genetically-engineered to minimize the production of any toxic effects for the patient receiving the therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group A single dose of HSV-1 (M032) | Experimental | Biological: M032 (NSC 733972)single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically or cytologically confirmed glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma.
- Prior therapy: Patients must have failed external beam radiotherapy to the brain, and if eligible and tolerated, undergone appropriate treatment with temozolomide chemotherapy. All radiation and additional chemotherapies must have been completed at least 4 weeks prior to enrollment. Prior therapy with nitrosoureas must have been completed at least 6 weeks prior to enrollment.
- Age ≥18 years (age of majority for clinical trials in Alabama). Because no dosing or adverse event data are currently available on the use of M032 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 (18 listed)
- Patients who have had chemotherapy, cytotoxic therapy, immunotherapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas), surgical resection within 4 weeks prior to entering the study, or have received experimental viral therapy or gene therapy at any time (e.g., adenovirus, retrovirus or herpes virus protocol). However, this does not preclude re-treatment with M032 at a later date.
- Patients 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.
- History of allergic reactions attributed to compounds of similar biologic composition to M032 or to IL-12.
- 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. Also, since M032 is a local treatment, patients whose tumors have bilateral extension through the corpus callosum, those with actively growing multifocal disease by MRI, and/or CSF dissemination/ leptomeningeal disease, are ineligible.
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 |
|---|---|---|
| M032 (NSC 733972)A single dose of HSV-1 (M032) infused through catheters into region(s) of tumor defined by MRI | Biological | Group A single dose of HSV-1 (M032) |
Primary outcome
Maximum Tolerated Dose (MTD) of M032
Time frame: baseline to12 months
3 secondary outcomes
Time to Progression Assessment
Time frame: baseline to 12 months
The Time of Survival Assessment
Time frame: baseline to 12 months
The Time of Biologic Assessment
Time frame: baseline to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 M. Markert, MD principal investigator
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 M032 (NSC 733972) in people with Recurrent Glioblastoma Multiforme and Progressive Glioblastoma Multiforme, 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 18 inclusion and 18 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 2 Oct 2025. 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?
Yes. Results are posted in the registry (first posted 2 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose (MTD) of M032 (time frame: baseline to12 months). 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 2 Oct 2025; AzTrials last refreshed its copy on 27 Oct 2026.