Phase 2a Study of CAN-2409 With Standard Radiation Therapy for Malignant Glioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2a Study of CAN-2409 With Standard Radiation Therapy for Malignant Glioma (NCT00589875), a na phase 2 study. The primary outcome is Number of Participants With Treatment Related Adverse Events.

2. Clinical Question

The central question is whether this combined treatment could be evaluated for safety in a population with malignant glioma, while also exploring potential clinical outcomes. In a single-group study, observations can describe what happened among participants receiving the regimen, but they cannot isolate the contribution of CAN-2409 from valacyclovir, radiation, temozolomide, surgery, or other influences. Without a concurrent comparator, changes in outcomes cannot establish how the same participants would have fared under a different treatment strategy.

The registry lists 52 participants enrolled. The adverse-event record uses a group of 43 participants at risk for its serious and other event summaries. The registry does not report why these denominators differ or give participant-level details that would explain the difference. The study was completed, but completion status alone does not establish that every planned outcome was measured or reported.

3. Trial Design

This is a Phase 2 study recorded as single group, with allocation marked not applicable and masking marked none. The registry lists an enrollment of 52 and a status of completed. The start is recorded as 2007-03 and primary completion as 2015-12. These dates describe the registry record; they do not, by themselves, explain the length of individual follow-up or the timing of every assessment.

The single arm is described as an extension of evaluation of the surgical resection arm, Arm B, from a Phase Ib study in which dose escalation on that arm had been completed. The registry does not report further details about the earlier study's results or how its participants relate to this study's participants. There is no randomized control arm in this record, so the design supports descriptive reporting of outcomes within the treated group rather than a randomized treatment-effect estimate.

The intervention list includes CAN-2409, valacyclovir, temozolomide and radiation therapy. The brief description says CAN-2409 was injected into the resection bed after standard tumor surgery, followed by valacyclovir pills for 14 days, with standard radiation and chemotherapy also administered. It describes CAN-2409 as an adenoviral vector engineered to express the Herpes thymidine kinase gene. Further details of dose, treatment schedules beyond the 14-day valacyclovir course, eligibility criteria, and protocol deviations are not reported in the registry record.

Overall survival is listed as a secondary outcome, and the primary endpoint is a count of participants with treatment-related adverse events over 2 months. The record lists four outcome measures but does not provide numerical overall-survival results or a complete set of analyses. The number of analyses recorded is 0. This does not establish why results are absent; the reason is not reported in the registry record.

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.

Enrollment to Treatment Initiation

Reasons for not completing this period:

Treatment Initiation to Completion

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.

Population: All patient who initated experimental treatment in the study

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Related Adverse Events, measured over 2 months.

The primary endpoint is the number of participants with treatment-related adverse events during a 2-month timeframe. It is a participant count: it concerns whether participants experienced an event, rather than the total number of separate episodes. The registry gives the endpoint title and unit but does not report an endpoint-specific numerical result, an operational definition of treatment-relatedness, or details on how events were assessed.

Safety endpoints of this kind are used to characterize the kinds and frequency of harms observed during a treatment regimen. Counting participants can make the measure more interpretable than counting every event when one participant may experience multiple events. However, a participant count does not convey the number, duration, severity, or clinical course of all events. Those details require separate reporting.

The posted adverse-event summary lists serious and other events for 43 participants at risk. It reports 20 participants affected by serious events and 40 affected by other events. Those summaries are not, by themselves, a complete account of the primary endpoint's treatment-related classification: the registry does not report whether those event counts use the same attribution criteria or timeframe as the primary endpoint. They should therefore be read as the posted safety summaries, not assumed to be an endpoint-specific result without further definition.

The endpoint can describe safety observations in this group, but a single-group count cannot determine how many events would have occurred under another regimen or without the study treatments. It also cannot establish that any event was caused by a particular component of this combination.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What can a single-group design estimate?

In general, a single-group study describes outcomes among participants who receive the study regimen. For a binary outcome, the basic descriptive information is how many participants experienced an event and how many were assessed or at risk. A comparison of treatment strategies requires a suitable contrast, usually a concurrent control group or another defensible design. This study is recorded as single group, with no allocation to different study arms, so its reported counts are not a randomized comparison.

Without a concurrent comparator, differences from an external expectation or from other studies can be affected by differences in participant characteristics, care, assessment, follow-up, and time. The registry record does not report a comparative analysis. Consequently, the event counts should be interpreted as observations in this study group, not as estimates of how many events the regimen prevented or caused relative to another option.

How should participant counts be understood?

In general, a count of participants with an event records each participant as affected or not affected under the endpoint definition. This differs from an event count, which may include multiple episodes in one participant. The primary outcome is titled as a number of participants with treatment-related adverse events, while the safety summary separately lists serious and other adverse-event counts. The record does not give enough endpoint-definition detail to establish that every item in the safety summary maps directly to the primary endpoint.

When interpreting any count, its denominator and observation window matter. The posted summaries identify 43 participants at risk for both serious and other events. The primary endpoint's timeframe is 2 months. The registry does not report a fuller account of the observation window used for the safety-summary counts, nor why the at-risk groups are smaller than the enrolled group of 52. No additional denominator should be inferred.

What does precision mean?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical model and indicates the uncertainty around an estimate. It does not show that all values in the interval are equally plausible, and it does not correct biases caused by study design or missing data. The registry does not report confidence intervals for the safety counts or numerical estimates for overall survival. Precision therefore cannot be assessed from the registry record beyond the fact that the reported summaries are based on the stated at-risk group.

In general, binary-outcome methods often use a binomial model, which treats each participant's outcome as an event or no event over a defined period. Such methods rely on a clear outcome definition and an appropriate denominator. If participants' outcomes are dependent, or if event risk varies substantially across unaccounted groups, simple models may not reflect all uncertainty. Over-dispersion is a general term for variation greater than a model expects; addressing it can matter when such a model is used. The registry does not report a fitted model, an over-dispersion assessment, or any adjustment for clustering or differing risk.

How do planning calculations differ from observed results?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, allocation, and analysis method. It is not a finding from enrolled participants, and it is not observed power. The planning assumptions described for this record use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. Those assumptions describe a hypothetical two-arm calculation, not the actual single-group design recorded for this trial.

The record does not report the trial's own sample-size justification, target effect, or a statistical plan that would establish how those planning assumptions relate to the study. Any illustrative calculation using such assumptions should not be read as evidence that the completed study had a particular power or was designed to detect a particular clinical effect. Sample-size illustrations are not observed treatment effects and cannot supply the missing randomized comparison.

What analyses are documented?

The registry lists four outcome measures and records zero analyses. The analysis populations, statistical methods for overall survival, handling of censored observations, missing-data methods, and adjustment for multiple outcomes are not reported in the registry record. These omissions limit assessment of how outcome summaries were constructed and whether the analyses followed a prespecified plan. They do not establish that no analyses were conducted outside the information in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Single Arm")
n      <- c(43)
events <- c(21)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Single Arm  43  21  48.8  33.3  64.5  34.6  63.2  34.6  63.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, including the primary adverse-event endpoint and overall survival as a secondary outcome. The number of analyses recorded is 0. The record does not report a statistical plan specifying which outcomes were confirmatory, how multiple outcomes or repeated analyses were handled, or whether any adjustment for multiplicity was used. It is therefore not possible to determine how the chance of a false-positive finding across multiple tests was addressed.

Missing-data methods and analysis populations are also not reported in the registry record. In particular, the reason that 43 participants are listed at risk for safety summaries while enrollment is 52 is not reported. The record does not state whether these figures reflect different analysis populations, unavailable assessments, exclusions, or another explanation. No assumption about the missing participants' outcomes is justified by the posted information.

Overall survival is named as a secondary outcome, but the record does not provide a numerical result, follow-up distribution, censoring details, or analysis method. In general, time-to-event analyses account for participants whose outcome is not observed by the end of follow-up, but the methods used are not reported. The reported deaths cannot be treated as an overall-survival estimate because the record does not specify the relevant timing or provide the analysis.

These gaps restrict reproducibility and make it difficult to evaluate selective outcome reporting, the effect of missing observations, and the precision of any result. They do not establish that outcomes were omitted deliberately or that the analysis was inappropriate; the reasons are not reported in the registry record.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fever (9.3%), thrombosis embolism (9.3%), cerebral edema (7.0%), seizure (7.0%), cognitive disturbance (4.7%).

The adverse-event summary reports a single group. For serious events, 43 participants are listed as at risk and 20 as affected. For other events, 43 are listed as at risk and 40 as affected. It also reports 41 deaths. The registry does not explain the relationship between the enrolled group of 52 and these at-risk counts, or give enough information to interpret the deaths by timing, cause, or treatment relationship.

The listed serious-event terms are Fever (9.3%), Thrombosis Embolism (9.3%), Cerebral Edema (7.0%), Seizure (7.0%), Cognitive Disturbance (4.7%), and Mood Alteration - Depression (4.7%). These percentages should be read as reported, not recalculated. The record does not state in this summary whether the same participant could appear under multiple terms or provide a term-specific denominator.

Serious and other event categories are not interchangeable, and the affected-participant counts do not represent the total number of episodes. The registry's primary endpoint specifies treatment-related adverse events over 2 months, but the safety summary does not provide enough detail to confirm that every count uses that same definition and timeframe. The counts describe what the record reports in the study group; without a comparator, they do not establish how the frequency would differ under another treatment.

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

The record supports a limited descriptive reading: a completed, single-group Phase 2 study enrolled 52 participants, and its adverse-event summary reports counts among 43 participants at risk. It also lists several serious-event terms and their reported percentages. Those observations help describe what was recorded in this group, but they do not by themselves establish the cause of an event, the risk attributable to an individual component, or how outcomes compare with another treatment.

The primary endpoint is treatment-related adverse events over 2 months, but the registry does not provide a detailed endpoint-specific result or operational definition of treatment-relatedness. The serious and other event counts should therefore be interpreted as posted safety summaries rather than assumed to be a complete numerical answer to the primary endpoint. The registry also lists overall survival as a secondary outcome without reporting a numerical estimate or analysis.

The single-group design cannot show what would have happened to similar participants under standard therapy alone or another regimen. This matters because the described treatment combines CAN-2409, valacyclovir, radiation therapy and temozolomide, following surgery. Any observed outcome could reflect several parts of care and other influences. The registry does not report a concurrent randomized control, so a treatment effect relative to another option cannot be estimated from this record.

The absence of a reported survival result should not be interpreted as evidence of benefit, lack of benefit, or no change. Likewise, the posted safety counts should not be converted into a claim that the regimen is safe or unsafe in a broader population. They are summaries for the recorded group, with limited information about denominators, follow-up, and event attribution.

Overall, the registry record documents the study's design, treatment components, primary safety question, and selected safety counts. It does not provide the comparative or outcome detail needed to establish efficacy or to quantify the precision of survival findings. The registry's stated hypothesis is a study rationale, not a result.

14. Why This Trial Matters Statistically

This study is statistically notable because it asks safety and potential-efficacy questions in a single-group setting, while the treatment includes several components. This design can be useful for recording outcomes during an intervention, but it places an important boundary on interpretation: without a concurrent comparator, observed outcomes cannot identify the effect of CAN-2409 separately from valacyclovir, radiation therapy, temozolomide, surgery, or other factors.

The record also illustrates why denominators and endpoint definitions are essential. Enrollment is 52, while the safety summaries list 43 participants at risk. Without an explanation, readers cannot determine why those denominators differ or whether the safety counts represent the same population and observation period as the primary endpoint. The primary endpoint focuses on treatment-related events over 2 months, while the safety summary presents serious and other events without enough detail to verify equivalence of definitions.

Overall survival is listed as a secondary outcome, but numerical survival results and analytic details are not reported. This gap prevents interpretation of that outcome and highlights the distinction between naming an outcome and publishing an analyzable result. The registry lists four outcome measures but records zero analyses, leaving the statistical approach, missing-data handling, and multiplicity strategy unclear.

These features make the record a useful example of how design and reporting determine what can be concluded. Descriptive counts can convey the reported experience of participants, but they are not substitutes for a controlled comparison, a clearly defined analysis population, and uncertainty estimates. The record's treatment hypothesis and completion status do not fill those statistical gaps. Careful reading therefore separates the documented safety observations from conclusions that require comparative or more complete outcome data.

15. 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.

The main design limitation is the absence of a comparator. Allocation is recorded as not applicable, masking as none, and the study model as single group. As a result, the record does not support a randomized contrast with another regimen. The combination includes CAN-2409, valacyclovir, radiation therapy and temozolomide, and the brief description also refers to tumor surgery. The contribution of any one component cannot be isolated from the posted design.

The registry does not explain why the safety summaries list 43 participants at risk when enrollment is 52. It does not report participant flow, reasons for non-inclusion in a safety summary, or the analysis population for each outcome. This prevents assessment of how the difference affects interpretation. Event definitions, attribution procedures, and follow-up details beyond the primary timeframe are also not reported in the registry record.

The record lists overall survival as a secondary outcome but provides no numerical result or analysis details. It does not report confidence intervals or other measures of precision for the posted event summaries. The number of analyses is recorded as 0, and the statistical plan, missing-data handling, and multiplicity approach are not reported. These omissions limit reproducibility and prevent evaluation of whether the reported outcomes were analyzed as planned.

The registry gives an enrollment of 52, but does not report detailed participant characteristics, subgroup results, or sufficient information to judge how broadly the observations apply beyond the study group. The reason for the long interval between the recorded start and primary completion dates is not reported. These limitations do not determine the direction of any treatment effect; they define what can be inferred from the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 2a Study of CAN-2409 With Standard Radiation Therapy for Malignant Glioma — NCT00589875.
• Registry record last updated 2024-04-03; status last verified 2024-03.
• Results first posted 2024-04-03.
• 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.

19. Record Summary

NCT00589875 is a completed Phase 2 study titled “Phase 2a Study of CAN-2409 With Standard Radiation Therapy for Malignant Glioma.” It is recorded as a single-group study with no masking, an enrollment of 52, a start of 2007-03, and primary completion in 2015-12. The sponsor is Candel Therapeutics, Inc.

The listed interventions are CAN-2409, valacyclovir, temozolomide and radiation therapy. The primary endpoint is the number of participants with treatment-related adverse events over 2 months. Overall survival is listed as a secondary outcome. The safety summary lists 43 participants at risk for serious and other events, with 20 affected by serious events, 40 affected by other events, and 41 deaths. Serious-event terms and reported percentages are listed in the safety summary.

The registry does not report numerical overall-survival results, a concurrent control comparison, or the statistical analysis details needed to assess outcome precision. It also does not explain the difference between enrollment and the safety at-risk group.