Bavituximab With Radiation and Temozolomide for Patients With Newly Diagnosed Glioblastoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bavituximab With Radiation and Temozolomide for Patients With Newly Diagnosed Glioblastoma (NCT03139916), a na phase 2 study. The primary outcome is Overall Survival at 12 Months (OS12).

2. Clinical Question

3. Trial Design

This was a phase II, single-group clinical trial sponsored by Massachusetts General Hospital. The registry record lists the study as completed, with enrollment of 36. Its recorded start date is 2017-09-13 and its primary completion date is 2022-08-31. Allocation is listed as NA and masking as none. Those design features mean the record describes a treatment group rather than a randomized, masked comparison between treatment groups.

The regimen combined bavituximab with radiation and temozolomide for patients with newly diagnosed glioblastoma. The arm description specifies a 6-week chemoradiation cycle: radiation was administered per standard of care, bavituximab 3 mg/kg was given by intravenous administration weekly starting during the first week, and temozolomide 75/m2 was taken orally once daily. The description then begins to describe a 4-week cycle but ends before its treatment details are complete. The remaining schedule is not reported in the registry record.

The listed outcomes include radiographic response rate, progression-free survival, and overall survival, in addition to the primary 12-month overall-survival endpoint. Although these outcomes describe different aspects of disease status and time to events, their numerical results and analysis details are not reported in the record available for this analysis. The record lists 0 analyses.

Because there is no concurrent control group, the design can describe outcomes and events observed in the treated group, but it cannot by itself separate treatment effects from other explanations for those outcomes. The registry record does not report a statistical analysis plan, randomization procedure, or masking procedure beyond the design entries noted above. Any such details beyond those entries are 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.

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.

6. Primary Endpoint

The registry lists the primary outcome as Overall Survival at 12 Months (OS12), measured over 12 months.

The primary endpoint is overall survival at 12 months, expressed as a percentage of participants. Overall survival is defined as time from study entry to death from any cause. The endpoint asks whether a participant is alive 12 months after study entry, and the reported percentage would describe the proportion meeting that status under the registry’s endpoint definition.

The record specifies a 95% confidence interval as the measure of dispersion. A confidence interval communicates statistical uncertainty around an estimated percentage: a narrower interval indicates greater precision, while a wider interval indicates less precision. It does not guarantee that the true value lies within the interval, and it does not address possible bias in how participants were selected, followed, or analyzed.

The endpoint definition states that participants lost to follow-up before a documented death are counted as deaths at the last assessment date when they were known to be alive. This is part of the stated endpoint rule, not a numerical result. The registry record does not report the primary endpoint estimate or its confidence interval, so neither the observed percentage nor its precision can be assessed from this record.

Overall survival is a clinically interpretable time-to-event outcome because it concerns death from any cause rather than a measure requiring attribution to a particular cause. In this trial, however, the endpoint definition alone does not establish what the observed survival was. The numerical result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how observations are converted into estimates and how uncertainty is expressed. The registry record identifies the primary endpoint as a percentage of participants and names a 95% confidence interval for dispersion. It does not report the numerical estimate, the interval, or the calculation method. The explanations below are general statistical context, not claims about an unreported analysis used in this study.

What does a percentage endpoint describe?

For a binary endpoint, each participant is classified according to whether the specified condition is met. A percentage summarizes the share meeting that condition in the group being analyzed. For this trial’s primary endpoint, the condition is being alive 12 months after study entry. The percentage would be an estimate for the study group, not a guaranteed value for every person with glioblastoma and not a direct comparison with another treatment.

Such an estimate depends on how the analysis population is defined and how outcome status is established. The record gives the endpoint rule for participants lost to follow-up before a documented death: they are counted as deaths at the last assessment date when known to be alive. It does not state the number of participants affected by that rule, how follow-up was completed, or whether additional handling of missing data was used. Those details are not reported in the registry record.

What does a confidence interval add?

A confidence interval expresses uncertainty arising from sampling variability under a statistical method. It gives a range of values compatible with the data and that method, rather than a single point estimate alone. The stated 95% confidence level describes the long-run performance of the interval procedure under its assumptions; it is not a 95% probability statement about this particular interval after it has been calculated. No interval endpoints are reported for the primary outcome, so its width and the precision of the estimate cannot be assessed.

Confidence intervals do not remove systematic sources of error. For example, incomplete follow-up, differences between enrolled participants and a wider clinical population, or differences in outcome assessment may affect how representative an estimate is. A statistical interval generally reflects uncertainty according to the calculation, not every possible source of bias or uncertainty in study conduct.

Why does the single-group design matter?

In a randomized comparison, treatment groups can be compared under a design intended to balance measured and unmeasured characteristics on average. This study is listed as single-group, with allocation recorded as NA and masking as none. There is therefore no randomized control group within the trial. A percentage estimated among treated participants can describe that group, but it cannot by itself show what would have happened to the same participants under a different treatment.

External comparisons require caution because studies may differ in who was eligible, how outcomes were defined, how follow-up was conducted, and when care was delivered. Statistical adjustment can address measured differences only when the necessary information and methods are available; it cannot ensure that all differences have been removed. The registry record does not report an external comparison or an adjustment analysis.

What does the sample-size planning note mean?

The registry record includes a planning illustration based on the observed effect. It describes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. It also distinguishes planning for a time-to-event outcome using a total event count from planning for other outcomes using participants per arm. These are assumptions for an illustration, not a description of this trial’s single-group design.

A planning calculation asks how much information a hypothetical study might need to detect a specified effect under stated assumptions. It is not evidence that the trial achieved a particular level of power, and it does not show that an effect was observed. Sample-size calculations based on an observed effect can also be sensitive to how that effect was estimated. The registry record does not report numerical planning results in the information available for this analysis, and the illustration should not be read as the trial’s own design or as observed power.

How should time-to-event outcomes be understood?

Overall survival and progression-free survival are time-to-event outcomes: they concern the time until a defined event. General methods for these outcomes can account for participants whose event has not been observed by the end of follow-up, provided the necessary follow-up and censoring information is available and the method’s assumptions are appropriate. The registry record names these outcomes but does not report their estimates, event definitions beyond the primary overall-survival definition, follow-up summaries, or analysis methods. It is therefore not possible to determine which time-to-event methods were used.

The stated sample-size note refers to a total number of events for time-to-event planning. That is a planning convention in the note, not a reported event target or a result. The record does not identify a statistical plan, interim analyses, or a sample-size justification. Those details are not reported in the registry record.

Finally, a statistical test and an estimate answer different questions. A test evaluates data relative to a null hypothesis under specified assumptions; an estimate describes the size of an outcome, while an interval communicates precision. No primary estimate, confidence interval, or test result is reported in the registry record. Statistical concepts can explain how such results would be read, but cannot fill in the unreported values.

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("Bavituximab + Standard of Care Radiation + Temozol")
n      <- c(33)
events <- c(24)
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  Bavituximab + Standard of Care Radiation + Temozol  33  24  72.7  54.5  86.7  55.8  84.9  55.6  84.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary endpoint of overall survival at 12 months and names radiographic response rate, progression-free survival, and overall survival among the secondary outcomes. It records 4 outcome measures and 0 analyses. The numerical results for these endpoints, the order in which they were analyzed, and any distinction between confirmatory and exploratory analyses are not reported in the registry record.

Multiplicity arises when several outcomes or statistical tests are considered. In general, testing many hypotheses can increase the chance of at least one apparently unusual result if each is assessed without accounting for the others. Researchers may address this through a prespecified hierarchy, adjustment procedures, or by treating secondary analyses as exploratory. The registry record does not report whether any multiplicity strategy was planned or used, so no conclusion can be drawn about adjustment of statistical inference.

The primary endpoint definition specifies how participants lost to follow-up before a documented death are classified: they are counted as deaths at the last date they were known to be alive. The record does not state how many participants were affected, whether other missing-data methods were applied, or how missing information was handled for the secondary outcomes. Those details are not reported in the registry record.

The analysis population is also not described in the information available. It is not reported whether analyses included all enrolled participants, only participants meeting additional criteria, or another defined group. The registry record does not describe an intention-to-treat population or a per-protocol population. Without these details, it is difficult to assess how closely an outcome estimate would correspond to the enrolled group or whether exclusions could affect interpretation.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: seizure (8.3%), hydrocephalus (5.6%), somnolence (5.6%), cognitive disturbance (2.8%), general disorders and administration site conditions - other, specify (2.8%).

The registry record reports one treatment group, with 36 participants at risk for serious adverse events and 9 affected. For other adverse events, it reports 36 at risk and 33 affected. These are descriptive counts for the listed group; no concurrent comparison group is reported. The record also lists 29 deaths, but does not provide enough information to determine their timing, causes, or relationship to treatment. The death count should not be treated as the primary 12-month survival result.

The most frequent serious adverse event terms listed are Seizure at 8.3%, Hydrocephalus at 5.6%, and Somnolence at 5.6%. Cognitive disturbance is listed at 2.8%, as are General disorders and administration site conditions - Other, specify and Nervous system disorders - Other, specify. These are registry-reported percentages; the record does not give participant counts for each term or explain how the percentages were calculated.

Event terms are not necessarily mutually exclusive: a participant may experience more than one kind of event. The record does not indicate whether that occurred for these terms. Counts of participants affected also do not convey severity, duration, timing, or attribution. Without a control group, these figures describe events recorded during the study but do not establish whether the regimen caused them or how the rates compare with another treatment.

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

The record identifies a phase II study of bavituximab with radiation and temozolomide in newly diagnosed glioblastoma, and it defines overall survival at 12 months as the primary endpoint. It also records adverse-event counts and names secondary outcomes. These details establish what the study set out to assess and provide some descriptive safety information.

However, the registry record does not report the numerical primary endpoint estimate or its 95% confidence interval. It therefore does not show what percentage of the study group was alive 12 months after study entry, or how precise that estimate was. Secondary outcome results are also not reported in the information available. A completed study status alone does not indicate the direction, size, or certainty of any outcome.

The single-group design is another important boundary. Even if an outcome estimate were available, it would describe the treated group rather than provide a randomized comparison against another regimen. The study record cannot establish from its design alone what would have happened to the same participants under an alternative treatment. It also cannot establish that an observed event was caused by treatment simply because it occurred during the study.

The reported serious and other adverse-event figures are counts within the treatment group. They do not supply comparative risks, and the term percentages do not by themselves describe event timing or severity. The record does not report enough detail to link the listed 29 deaths to a specific cause or to infer the 12-month overall-survival percentage.

In short, the available record supports a description of the design, regimen, endpoint definition, and selected safety figures, but not a quantitative conclusion about the primary survival outcome. It neither demonstrates benefit nor establishes lack of benefit. Interpreting treatment effects would require outcome estimates and uncertainty measures, and a suitable comparison would be needed to support a causal contrast.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a clear endpoint definition and a study design constrain what can be concluded. Overall survival at 12 months is an interpretable endpoint, and the registry record specifies how it is defined and how one form of loss to follow-up is handled. Yet without the numerical estimate and confidence interval, readers cannot assess the observed survival percentage or its precision. A well-defined question and a reported answer are both needed for quantitative interpretation.

The single-group design also makes the distinction between description and comparison especially important. Outcomes among treated participants can characterize what was recorded in the study, but they do not supply a randomized counterfactual. This matters whenever the clinical question concerns whether an intervention changes outcomes compared with another approach. The design should shape the language used to describe any result, not merely the statistical calculation applied to it.

The record’s planning note offers another useful distinction: a sample-size illustration is not the trial’s observed power and is not itself evidence of an outcome. Its assumptions describe a hypothetical planning exercise, including equal allocation between two arms, even though the trial is listed as single-group. Keeping planning calculations separate from trial results prevents a hypothetical design scenario from being mistaken for evidence generated by the study.

Finally, outcome counts and adverse-event descriptions need context. Counts, percentages, definitions, follow-up, and analysis populations each contribute different information. When details such as numerical survival results, analysis methods, missing-data handling, and comparison groups are absent, the correct statistical conclusion is limited rather than speculative. This trial record illustrates why design, estimation, precision, and transparent reporting must be considered together.

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 limitation for interpreting outcomes is that the registry record does not report the numerical primary endpoint result or its 95% confidence interval. It also does not report numerical results for the named secondary outcomes. The primary question is therefore identifiable, but its answer and precision cannot be assessed from the record available for this analysis.

The study is listed as single-group, with allocation NA and masking none. There is no concurrent randomized control group in the described design, which limits causal comparison. The record does not report a control regimen or an external comparator. Any comparison with outcomes from another source would need to account for differences in participants, care, follow-up, and outcome definitions, and no such analysis is described.

The treatment description is incomplete after the start of the 4-week cycle. The registry record states the first 6-week chemoradiation cycle and gives the listed dosing details, but it does not provide the remainder of the schedule in the available arm description. It also does not describe participant characteristics, eligibility details, follow-up completeness, or the analysis population. These details are not reported in the registry record.

For safety, the record reports group-level counts and selected serious adverse-event terms but does not provide event timing, attribution, term-specific counts, or comparative rates. It lists 29 deaths, but their timing and causes are not reported in the information available. The record does not describe a multiplicity strategy, a statistical analysis plan, interim analyses, or sample-size justification. These omissions limit interpretation and should not be filled with assumptions about how the study was conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Bavituximab With Radiation and Temozolomide for Patients With Newly Diagnosed Glioblastoma — NCT03139916.
• Registry record last updated 2024-05-16; status last verified 2024-05.
• Results first posted 2024-05-16.
• 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

NCT03139916 is a completed phase II, single-group trial sponsored by Massachusetts General Hospital. It studied bavituximab with standard-of-care radiation and temozolomide for newly diagnosed glioblastoma and lists enrollment of 36. The recorded study start date is 2017-09-13, and the primary completion date is 2022-08-31. Allocation is listed as NA and masking as none.

The primary endpoint is overall survival at 12 months, expressed as a percentage, with a 95% confidence interval specified for dispersion. The registry record defines the endpoint but does not report its numerical estimate or confidence interval. Secondary outcomes include radiographic response rate, progression-free survival, and overall survival. The record lists 4 outcome measures and 0 analyses.

For the treatment group, the adverse-event record reports 9 participants with serious adverse events among 36 at risk, 33 with other adverse events among 36 at risk, and 29 deaths. These are descriptive figures without a control group. Numerical results for the primary and secondary efficacy outcomes are not reported in the registry record.