Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma (NCT02062827), a na phase 1 study. The primary outcome is Maximum Tolerated Dose (MTD) of M032.

2. Clinical Question

The trial addresses an early-stage dose and safety question rather than a comparative treatment-effect question. In a phase 1 study, dose-related safety information can help characterize tolerability and inform later research, but a single-group design does not establish how outcomes compare with another treatment or with no M032. The registry lists 29 participants enrolled and records the study as completed. It identifies time to progression, time of survival, and time of biologic assessment among secondary outcomes, but does not report their definitions or analyses in the record.

The stated population includes several glioma diagnoses, while the brief summary distinguishes patients by whether surgery is an option or would be beneficial. The record does not explain how those descriptions relate to the listed group or to each dose cohort. Consequently, the clinical question should be read as a dose-finding and safety question in the population described, not as a claim about efficacy in a specific subgroup.

3. Trial Design

This is a phase 1, completed, single-group study sponsored by the University of Alabama at Birmingham. The registry records enrollment of 29 participants. Allocation is listed as not applicable, and masking is listed as none. There is no separate control arm in the record, so the dose groups cannot serve as randomized comparisons of M032 against another intervention.

The listed intervention is M032 (NSC 733972), classified as a biological intervention. The arm description says that a single dose of HSV-1 (M032) was infused through catheters into tumor region or regions defined by MRI. Adverse-event records are organized by dose: 10^5, 10^6, 10^7, 10^7.5, 10^8, 10^8.5, and 10^9. These are dose groups, not independent control arms. The registry record does not give the method used to assign participants to dose groups, the rules for moving between doses, or the criteria used to stop dose escalation.

The trial began on 2013-11-25 and has a primary completion date of 2022-09 in the record. These administrative dates and the completed status do not establish that every planned outcome was analyzed or reported. The registry lists a primary endpoint titled “Maximum Tolerated Dose (MTD) of M032,” measured in plaque-forming units (PFU), with the timeframe recorded as “baseline to12 months.” It does not give a numeric MTD result.

The record’s summary describes safety and tolerability aims in patients who would not be eligible for surgical resection and patients who would benefit from surgical resection. How those aims were implemented in the study groups is not reported in the registry record. The record also does not describe eligibility criteria in detail, the treatment administration schedule beyond the single dose, follow-up procedures, or the statistical plan. Those details should not be inferred from the dose-group listing or the study’s phase.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of M032, measured over baseline to12 months.

The primary endpoint is titled “Maximum Tolerated Dose (MTD) of M032.” Its measurement unit is plaque-forming units (PFU), and its recorded timeframe is “baseline to12 months.” The registry does not provide a numeric MTD, a definition of dose-limiting toxicity, or the rule used to decide that a dose was tolerated. Therefore, the endpoint’s title describes the target of measurement, but the posted record does not show the endpoint’s result or how it was determined.

General statistical context: dose-finding studies often seek a tolerable dose while monitoring safety, because the decision concerns the balance between dose and observed toxicity. An MTD is not automatically the most effective dose; it is a safety-oriented dose concept. The exact operational definition matters. For example, the protocol would need to specify which events count toward dose-limiting toxicity, the observation period for those events, and how the dose decision uses the observed data. Those protocol details are not reported in the registry record and cannot be reconstructed from the adverse-event counts alone.

A dose estimate is more informative when accompanied by the underlying event definition, the number of participants evaluated at each dose, and a measure of uncertainty. The registry reports safety counts by dose group, but does not connect them to an MTD decision or provide an uncertainty interval for the primary endpoint. The listed secondary outcomes include time to progression, time of survival, and time of biologic assessment; their definitions and numerical results are not reported in the registry record. As a result, the endpoint can be described, but its estimate and precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design is single-group, with no randomized control arm listed. The allocation field is not applicable and masking is listed as none. Those features matter because dose groups are not equivalent to treatment and control groups: participants in each group received a listed dose of M032, and the record does not describe random assignment among doses. Differences in observed events across these groups cannot be attributed to dose alone from the registry counts.

What does an MTD endpoint represent?

General statistical context: a maximum tolerated dose is a dose-finding target based on observed safety, rather than a direct measure of benefit. To interpret an MTD, readers need the protocol’s definition of a dose-limiting event, the window in which it is counted, the number of participants evaluated at each dose, and the decision rule for selecting a dose. The registry names the MTD endpoint and gives PFU as its unit, but does not report those operational details or the numeric endpoint result. The listed adverse-event counts are not enough to reconstruct the protocol’s dose decision.

How should dose-group counts be read?

General statistical context: a count reports how many participants met a recorded event category among those assessed or at risk. It does not convey when an event happened, how long participants were followed, whether a participant had more than one event, or whether the event was attributed to treatment. The record gives at-risk and affected counts for serious and other adverse events by dose, but does not define the “other” category or provide event-level timing and attribution. For small cohorts, counts can vary markedly with the experience of an individual participant. They should be treated as descriptive unless a suitable analysis and its assumptions are reported.

For the serious adverse-event measure, the record lists at-risk and affected counts separately for every dose group. It also lists deaths within those groups. These are distinct pieces of descriptive safety information: the death counts should not be read as treatment-related deaths, and the serious-event counts do not state that every recorded event was caused by M032. The record does not provide the clinical adjudication or causal-attribution details needed to make those interpretations.

What would uncertainty measures add?

General statistical context: a confidence interval describes a range of values compatible with the data under a specified statistical model. It makes the uncertainty around an estimate visible; a point estimate alone does not. With small groups and count outcomes, uncertainty can be substantial. No confidence interval for the MTD or adverse-event comparisons is reported in the registry record. It is therefore not possible to assess the precision of a dose estimate or to determine whether apparent differences among the listed dose groups would remain after accounting for sampling variability.

General statistical context: over-dispersion occurs when count variability exceeds what a simple count model assumes. When present, it can make standard errors too small if the model does not account for the extra variation. Whether over-dispersion is relevant depends on the outcome and analysis model. The registry record does not report a count-model analysis, its assumptions, or any assessment of over-dispersion, so this issue cannot be evaluated for the trial’s reported results.

What do the secondary outcomes add?

The registry names time to progression, time of survival, and time of biologic assessment as secondary outcomes. General statistical context: time-to-event outcomes concern the time until an event occurs and may require methods that account for differing follow-up or participants who have not experienced the event by the end of observation. Interpretation depends on the event definition, follow-up, censoring rules, and analysis population. Those details and outcome estimates are not reported in the registry record. The listed outcome names alone do not establish how progression, survival, or biologic assessment was defined or analyzed.

The record lists four outcome measures and no analysis records. This indicates that the registry record does not present analyses for those outcomes; it does not establish whether analyses were performed outside the registry or whether results were unavailable for another reason. Statistical methods, model specifications, adjustment variables, interim analyses, and the handling of missing data are not reported in the registry record.

How should planning illustrations be distinguished from trial results?

General statistical context: sample-size planning asks how many participants a future study might need under specified assumptions. The record’s planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set as a stated fraction of the observed effect. It describes participants per arm for 80% power and for 90% power for non-time-to-event outcomes, and a total number of events for time-to-event outcomes. These are planning illustrations based on an observed effect, not the trial’s own design justification and not observed power. The record does not report the protocol’s sample-size justification. Since this study is single-group and not a randomized two-arm comparison, such two-arm planning assumptions should not be mistaken for a description of its actual design.

In general, an analysis should be interpreted alongside its prespecified endpoint, population, missing-data approach, and model assumptions. Those components are not reported in the registry record. Without them, the posted counts can be described, but the rationale, precision, and robustness of any underlying analysis cannot be assessed.

10. Multiplicity, Missing Data and Analysis Populations

The registry names a primary MTD endpoint and lists secondary outcomes for time to progression, time of survival, and time of biologic assessment. It does not report a statistical analysis plan, the hierarchy among secondary outcomes, or any adjustment for multiple testing. When several outcomes are tested, multiplicity can increase the chance of a false-positive finding if the analyses are interpreted without an appropriate strategy. That is a general statistical concern; the record does not indicate whether or how it was addressed in this trial.

The record lists four outcome measures and no analysis records. It therefore does not present outcome-analysis results from which to assess multiplicity, model choice, or consistency across endpoints. It also does not report interim analyses, stopping rules, or any prespecified distinctions between confirmatory and exploratory analyses. Their presence or absence in the conduct of the trial cannot be inferred from the registry information.

Missing-data methods and analysis populations are not reported in the registry record. The record does not specify how many participants contributed to each outcome analysis, how participants with incomplete follow-up were handled, or whether the analysis population was defined by treatment received, eligibility, or another rule. For time-to-event outcomes, censoring rules and follow-up completeness are also not reported. These omissions limit interpretation because the number and characteristics of participants contributing to an outcome can affect the estimate and its precision.

General statistical context: multiplicity concerns are distinct from missing-data concerns. A prespecified testing strategy addresses how evidence is interpreted across outcomes, whereas missing-data methods address incomplete outcome information. Neither can be judged from outcome names and safety counts alone. The record does not provide enough analysis detail to evaluate either issue.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypertension (100.0%), surgical wound not healing (100.0%), fatigue (50.0%), headache (50.0%), aspiration (16.7%).

The safety record reports serious and other adverse-event counts by dose group, with the number at risk and the number affected. For serious adverse events, the affected counts are 0 among 4 at 10^5, 0 among 1 at 10^6, 0 among 1 at 10^7, 1 among 2 at 10^7.5, 1 among 6 at 10^8, 1 among 1 at 10^8.5, and 2 among 6 at 10^9. These counts describe the registry entries for each group; they do not show that an event was caused by M032.

The record lists serious-event terms including hypertension and surgical wound not healing, each with 100.0%; fatigue and headache, each with 50.0%; and aspiration and cerebral herniation, each with 16.7%. The denominator and dose-group context for these percentages are not reported in the registry record, so they should not be treated as dose-specific rates or compared directly with the at-risk counts. The record also lists deaths by dose group, but does not report their cause, timing, or attribution. A death count alone does not establish treatment causality.

General statistical context: adverse-event counts are descriptive and depend on definitions, observation periods, and the participants assessed. The record does not provide enough detail to infer severity patterns beyond the serious-event label, event duration, recurrence, or causal relation. Small dose groups also make counts an imprecise basis for comparing safety across doses. The listed figures should therefore be read as reported events within the registry record, not as proof of a dose-response pattern or of treatment-related harm.

12. What the Result Does, and Does Not, Mean

The record establishes that the study was completed, enrolled 29 participants, and evaluated a single-dose M032 intervention in a phase 1, single-group design. It reports the primary endpoint as maximum tolerated dose, measured in PFU, and records safety counts across dose groups. The adverse-event entries provide a descriptive account of participants at risk and affected in the registry’s categories. They do not include a reported numeric MTD result or a reported analysis connecting the event counts to a dose-selection decision.

The record does not establish that M032 improved survival, delayed progression, or changed biologic outcomes. Time to progression, time of survival, and time of biologic assessment are named as secondary outcomes, but numerical results and analysis details are not reported in the registry record. Nor does a single-group study provide a concurrent control comparison for estimating what would have happened without M032 or under another treatment.

The adverse-event figures should not be read as causal evidence. The registry lists affected counts and deaths by dose group, but does not provide attribution, timing, or a comparison group. The serious-event terms and percentages are not accompanied by a clear denominator in the record. As a result, they do not support a direct comparison of event rates across groups or a conclusion about treatment-related risk.

General statistical context: a result is most informative when its estimate, uncertainty, endpoint definition, analysis population, and analysis method are reported together. A missing registry result does not prove that no analysis was performed; it means the result is not available in the registry record. Likewise, completion status means the study is recorded as completed, not that all outcomes are reported. The statistical meaning of this record is therefore bounded: it describes the design and posted safety information, while leaving the primary endpoint result and secondary outcome analyses unreported.

13. Why This Trial Matters Statistically

This trial is statistically important as an example of a dose-finding question that should not be confused with a comparative efficacy question. The registry identifies an MTD endpoint and records several M032 dose groups, but lists no separate control arm. Consequently, the dose-group adverse-event counts are descriptive observations, not randomized evidence that one dose produced more or fewer events than another. This distinction is central when interpreting early-phase studies.

The record also illustrates why an endpoint title is not a result. “Maximum Tolerated Dose (MTD) of M032” identifies what the study sought to determine, but the registry does not report the numeric dose selected or the rule used to select it. Without the dose-limiting event definition, decision procedure, and uncertainty around the estimate, readers cannot assess how firmly the endpoint was determined from the posted record.

Safety reporting is valuable, but its interpretation depends on denominators and context. The registry gives counts by dose group and lists serious-event terms with percentages. The percentages’ denominators and relationship to specific dose groups are not clear in the record, and deaths are not accompanied by causal attribution. This makes careful separation of recorded events from treatment-related conclusions especially important.

Finally, the record names time-to-event and biologic secondary outcomes without reporting analyses. Statistical transparency requires more than listing outcomes: definitions, follow-up, analysis populations, missing-data handling, and uncertainty help readers understand what the estimates mean. Their absence in the registry record does not show that no work was done, but it limits what can be evaluated from the posted information. The study therefore matters statistically as a reminder to distinguish design intent, observed counts, endpoint estimates, and comparative evidence.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several trial-specific limitations constrain interpretation of the registry record. The study is listed as single-group, with allocation not applicable and no masking. There is no separate control arm, so outcomes cannot be compared against a concurrent control group. Although adverse-event counts are reported across dose groups, the method for assigning participants to those groups is not reported in the registry record. The groups therefore cannot be assumed to be exchangeable or to differ only by dose.

The primary endpoint is named but its numeric result is not reported. The record also does not provide the definition of dose-limiting toxicity, the decision rule for selecting an MTD, or uncertainty around the endpoint. Without those details, the reported safety counts cannot independently establish the MTD. The secondary outcomes are listed without definitions or numerical analyses.

The safety data have limited context. The record does not define the “other” adverse-event category, specify event timing or duration, or explain causal attribution. It lists deaths by dose group without reporting cause or relationship to intervention. Serious-event terms and percentages appear without a clear denominator or dose-group mapping. The small cohort counts make descriptive differences particularly difficult to interpret, and the record does not report statistical comparisons across dose groups.

Further details that are not reported in the registry record include the eligibility criteria in full, the relationship between the surgery-related descriptions in the summary and the listed group, the analysis populations, missing-data handling, follow-up completeness, interim analyses, and the statistical analysis plan. The registry’s completed status does not resolve these reporting gaps. These limitations concern what can be concluded from the record; they do not establish that the underlying study did not collect additional information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Genetically Engineered HSV-1 Phase 1 Study for the Treatment of Recurrent Malignant Glioma — NCT02062827.
• Registry record last updated 2026-11-04; status last verified 2026-10.
• Results first posted 2024-02-02.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT02062827 is a completed phase 1 study sponsored by the University of Alabama at Birmingham. It enrolled 29 participants with recurrent or progressive glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma. The intervention was a single dose of M032 (NSC 733972), a genetically engineered HSV-1 expressing IL-12, infused through catheters into MRI-defined tumor region or regions.

The study is recorded as single-group, with allocation not applicable and masking none. Its primary endpoint is maximum tolerated dose, measured in PFU, with the timeframe recorded as “baseline to12 months.” The registry does not report a numeric MTD result. It lists time to progression, time of survival, and time of biologic assessment as secondary outcomes, without reporting their analyses.

Adverse-event counts are reported across dose groups, along with serious-event terms, percentages, and deaths. The record does not provide enough context to infer treatment causality or compare event rates reliably. Statistical analysis details, analysis populations, and missing-data methods are not reported in the registry record.