Optune(NOVOTTF-100A)+ Bevacizumab+ Hypofractionated Stereotactic Irradiation Bevacizumab-Naive Recurrent Glioblastoma (GCC 1344): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Optune(NOVOTTF-100A)+ Bevacizumab+ Hypofractionated Stereotactic Irradiation Bevacizumab-Naive Recurrent Glioblastoma (GCC 1344) (NCT01925573), a na na study. The primary outcome is Number of Participants With a Grade 3 or High Toxicity/Adverse Event (Primary Measure).

2. Clinical Question

The study description frames the work as a pilot intended to generate preliminary safety and activity data. The combination brings together tumor treating fields delivered with Optune, bevacizumab, and focused, abbreviated-course brain irradiation. The registry’s primary measure emphasizes toxicity rather than a comparison of tumor outcomes. Although the study description refers to activity, the registry record does not report a primary activity outcome or statistical result for one.

The central statistical question is consequently descriptive: what toxicity observations were recorded among people treated in this single group, and how much information do those observations provide about the safety of the regimen? Without a control group, differences attributable to the combination cannot be separated from other explanations through a randomized comparison. The record also does not report the primary measure’s participant count or an analysis estimating its uncertainty.

3. Trial Design

This was a single-group pilot study sponsored by the University of Maryland, Baltimore. The registry lists the phase as NA, allocation as NA, and masking as none. Enrollment is recorded as 7. The study started in 2014-05, had a primary completion date of 2019-08, and is listed as terminated. The reason for termination is not reported in the registry record.

The listed treatment arm is Optune+RT+Bevacuzimab. Its description specifies bevacizumab every 2 weeks plus daily Optune in 4 week cycles. Radiotherapy was to begin after 3 rounds of bevacizumab, with the hypofractionated course chosen by the physician: 30 Gy in 5 fractions or 35 Gy in 10 fractions. The final described phase was adjuvant bevacizumab and Optune. The intervention list separately names Optune(NOVOTTF-100A) as a device. The registry does not provide further detail about how treatment was delivered or adherence was assessed.

A single-group design records outcomes in people receiving the regimen but does not assign participants to a concurrent control arm. It can describe events in the treated group, but it does not establish what would have happened to comparable participants under a different treatment or no study treatment. Allocation is not applicable as a between-arm assignment procedure in this record, and there is no masking.

The registry describes the work as a proposed pilot intended to generate preliminary data about safety and activity in bevacizumab-naive recurrent glioblastoma. However, the record does not report a statistical analysis plan, a sample-size justification, or the reason the study was terminated. Those details should not be inferred from the pilot label or the enrollment entry. The listed status and dates describe the registry record; they do not explain the conduct or outcome of the study.

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

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 Number of Participants With a Grade 3 or High Toxicity/Adverse Event (Primary Measure), measured over 6 months.

The primary measure is the number of participants with a Grade 3 or higher toxicity or adverse event, with a timeframe of 6 months. It is a count of participants, not a measure of event frequency per unit of follow-up. A participant-level count records whether participants met the specified event criterion; it does not by itself show how many separate events occurred or when they occurred.

The endpoint description connects this measure to the ability to complete the protocol’s three-modality treatment without undue acute toxicity. It defines thresholds for Grade 3 or higher nonhematologic toxicity, Grade 4 or higher nonhematologic toxicity, Grade 4+ scalp dermatitis, and Grade 2-3 scalp dermatitis. It also lists early stopping rules involving symptomatic CNS hemorrhages and treatment-related toxicities. These thresholds and rules describe the protocol’s safety criteria; they are not reported outcomes.

Safety endpoints are used to characterize harms observed during treatment and to assess whether the treatment burden fits the study’s stated tolerability criteria. A participant count can be easy to interpret, but it depends on the event definitions, observation period, and completeness of follow-up. The registry record does not report the primary endpoint result, the number who completed treatment, or how missing follow-up was handled. It therefore does not establish whether the stated thresholds were met.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods should be interpreted in relation to the design and the endpoint actually reported. This record describes a single-group study, a participant-count primary measure, and no listed statistical analyses. The registry record does not report the statistical analysis plan, endpoint analysis method, confidence intervals, or a model used for any outcome. The appropriate interpretation is therefore descriptive rather than inferential: the available results do not establish a treatment effect or a comparison with an alternative.

What does a participant count tell us?

The primary endpoint is a count of participants meeting the Grade 3 or higher toxicity or adverse-event criterion within the stated 6-month timeframe. General statistical explanation: a participant-level outcome treats each participant as having met or not met the defined criterion. This differs from counting every event, because one participant may experience more than one event. The registry record does not explain how repeated events were handled or provide a primary endpoint count.

For an event count to be interpretable, the event definition and observation period need to be clear. The record names grades and toxicity categories and gives a 6-month timeframe. It also describes thresholds for several categories and early stopping rules. The registry does not report whether those rules were triggered, how toxicity grades were assigned, or how outcomes were assessed. These are not details that can be inferred from the threshold definitions.

Why does the single-group design matter?

General statistical explanation: a control group can help distinguish outcomes associated with an intervention from outcomes that might also occur under another treatment or in the absence of that intervention. Random allocation, when used, supports comparability between groups on average, though it does not guarantee identical groups. This study is listed as single-group, so it has no concurrent comparator and no randomized between-group contrast. A within-group count can describe what was observed, but cannot estimate a controlled treatment difference.

The absence of a comparator also limits causal interpretation. The record describes bevacizumab-naive recurrent glioblastoma and a combination regimen, but it does not provide a basis for attributing every event in the group to one component or to the combination. The intervention includes Optune, bevacizumab, and radiotherapy, with radiotherapy schedule selected by physician choice. The record does not report analyses that separate the contributions of these components or schedules.

How should precision be understood?

General statistical explanation: a point estimate is a concise description of an observed outcome, while an interval estimate communicates uncertainty around that estimate under stated assumptions. Wider intervals indicate less precision. A small amount of observed information generally leaves more uncertainty than a larger amount, although the amount of uncertainty also depends on the event frequency and analysis method. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed from a reported interval.

Over-dispersion is a general issue when counts vary more than a statistical model expects. For example, repeated or clustered events can make observations less independent than a simple model assumes, which may make standard errors too small if the model ignores that structure. That concept does not establish that over-dispersion occurred in this trial. The primary measure is described as a count of participants, and the registry record does not report a model for participant counts or repeated events.

What can planning illustrations establish?

General statistical explanation: sample-size calculations describe planning under specified assumptions; they are not evidence that an observed trial had a particular probability of detecting an effect. Planning illustrations based on an observed effect are particularly dependent on that estimated effect and the assumptions used in the calculation. The listed assumptions describe two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and effects set as a stated fraction of the observed effect. They also distinguish participant counts per arm for most outcomes from total event counts for time-to-event calculations.

Those assumptions do not turn this single-group study into a two-arm comparison. Nor should a planning illustration be read as observed power or as proof that an effect is real. The registry record does not report an original sample-size justification or the trial’s own design calculations. No new sample-size result or power estimate can be inferred from the study enrollment alone.

What is not reported?

The registry record does not report the analysis population, missing-data approach, treatment of participants who discontinued, censoring rules, or a statistical model. It also does not report whether any interim analyses were planned or conducted. Since no statistical analyses are listed, no p-value, adjusted estimate, or inferential comparison is available for the primary measure. These absences do not establish that the study team did not consider these issues; they mean the details are not reported in the registry record.

General statistical explanation: multiplicity arises when several outcomes, comparisons, time points, or subgroup analyses are tested. If many hypotheses are examined without accounting for that process, the chance of at least one apparently notable result can rise. The record lists one primary outcome measure and does not list analyses, but it does not provide enough information to evaluate a prespecified testing strategy or any multiplicity adjustment. The intended primary measure and listed adverse-event terms should therefore not be treated as evidence of a formal hypothesis-testing plan.

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("Optune+RT+Bevacuzimab")
n      <- c(7)
events <- c(7)
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  Optune+RT+Bevacuzimab  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure, identifies it as primary, and lists no statistical analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, or an approach to multiple testing. Multiplicity therefore cannot be assessed beyond noting that the record does not describe a testing strategy. The presence of several toxicity thresholds and adverse-event terms does not, by itself, show whether these were planned as separate statistical hypotheses.

General statistical explanation: multiplicity can arise when investigators test multiple outcomes, comparisons, subgroups, or time points. Without a prespecified strategy, interpreting isolated results from many tests can be misleading. A plan may define a primary endpoint, set an order for testing, or adjust inference to account for multiple comparisons. The registry record does not say whether any such procedures were used.

The analysis population is not reported. The record does not say whether the primary measure was assessed among all enrolled participants, only participants who began treatment, or another defined group. It also does not report how withdrawals, incomplete follow-up, or missing toxicity assessments were handled. These details matter because missing outcomes can affect the interpretation of a participant count, especially when the endpoint has a specified 6-month timeframe.

Missing information should not be treated as proof that data were missing or that a particular method was used. The registry record simply does not report the analysis population or missing-data procedures. It also does not describe censoring, interim analyses, or a statistical plan. The reason for termination is not reported, and no conclusion about its effect on data collection is warranted.

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: hypertension (28.6%), seizure (28.6%), muscle weakness (14.3%), encephalopathy (14.3%), cranial- cn ii vision (14.3%).

The registry lists 7 participants at risk in the group for serious adverse events and 5 affected. It separately lists 7 at risk and 5 affected for other adverse events. These are separate registry categories, and the record does not say whether the people represented in the two affected counts overlap. The counts should not be added or interpreted as a count of unique participants.

The listed serious-event terms include hypertension and seizure at 28.6% each, and muscle weakness, encephalopathy, and cranial- CN II vision at 14.3% each. The registry also lists 1 death. It does not report the cause of death, its timing, or whether it was considered related to treatment. The record does not provide details about event duration, recurrence, or severity beyond the category names and the listed percentages.

These entries are descriptive safety information, not a comparison with another treatment. The record does not report a statistical analysis of these events or the primary toxicity endpoint result. It also does not establish that every listed event was caused by the regimen. General statistical point: event counts from a small group can be imprecise as estimates of how often events would occur in a wider population, and uncertainty cannot be fully judged without a defined analysis and its interval estimates.

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

The record documents a pilot study of a three-modality regimen for bevacizumab-naive recurrent glioblastoma. Its main stated safety question concerns higher-grade toxicity over 6 months and whether participants could complete protocol treatment without the specified undue acute toxicity. The registry record does not report a result for that primary measure. It therefore does not show whether the stated toxicity thresholds were met.

The adverse-event listing gives a descriptive account of events in the study group, including affected counts for serious and other adverse events, selected serious-event terms and one death. Those entries do not constitute a controlled comparison, and the record does not establish whether events were caused by treatment. They should not be interpreted as an estimate of the regimen’s safety relative to another approach.

The study description refers to preliminary safety and activity data, but the registry record does not report a statistical result for activity. It also does not give a treatment-effect estimate, confidence interval, or hypothesis test for the primary measure. The available entries therefore cannot support a conclusion about the size or precision of a treatment effect.

General statistical explanation: a pilot study can help describe feasibility, event types, and the practical uncertainties that might matter in further research. Its role is distinct from a controlled trial designed to estimate comparative effects. In this record, the single-group design and limited reported analysis mean that observed events can be described, but cannot be cleanly separated from background risks or other explanations.

The terminated status does not explain why the study ended. The registry record does not report whether termination was related to safety, activity, enrollment, or another reason. No conclusion about the reason or its consequences for the results should be drawn from status alone. The most defensible reading is limited: the registry describes the intended treatment and provides some adverse-event listings, while leaving the primary endpoint result and statistical analysis unreported.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a safety question and a comparative treatment question. Its primary measure is framed around whether treatment can be completed without specified toxicity, which is a descriptive safety objective. The study is single-group, however, so it cannot compare the regimen with a control treatment. That distinction matters whenever a reader moves from describing observed events to making claims about treatment effects.

The regimen combines Optune, bevacizumab, and hypofractionated stereotactic irradiation. Its treatment description also allows a physician choice between two radiotherapy schedules. Statistical interpretation must therefore keep the treatment package and its implementation in view: the registry does not report an analysis separating effects attributable to an individual component or schedule. A single pooled group description cannot answer those component-specific questions.

The record also illustrates the importance of reporting endpoint results and uncertainty. It defines a primary measure and toxicity thresholds, but does not report the primary result or an interval estimate. Without those, readers cannot tell from the record how many participants met the endpoint or how precise an estimate would be. Adverse-event listings offer useful descriptive detail, but they do not replace the endpoint analysis.

General statistical explanation: pilot studies can identify questions for further investigation, while estimates from small studies are often highly uncertain. A planning calculation is not a substitute for observed evidence, and a planning illustration based on an observed effect should not be described as observed power. Here, the record’s listed planning assumptions do not change the single-group design or establish a comparative result.

These distinctions are important for clinical researchers reading registry entries. Design, outcome definitions, missing-data handling, and analysis reporting jointly determine what conclusions are warranted. In this case, the available registry information permits a cautious description of the intended safety focus and posted adverse events, but not a comparative claim.

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 trial-specific limitation is the single-group design. There is no concurrent control arm, and allocation is listed as NA. The record therefore does not support a like-for-like comparison of the regimen against another strategy. It also cannot show whether observed events differ from what would have occurred under another treatment.

Enrollment is recorded as 7, and the registry does not report the primary endpoint result or any statistical analyses. This prevents assessment of the primary toxicity measure and its precision. The serious and other adverse-event groupings each list 5 affected, but the record does not state whether those groupings overlap. The listed terms and percentages do not include the event-level detail needed to interpret timing, recurrence, duration, or attribution.

The registry does not report the reason for termination, the analysis population, missing-data procedures, protocol adherence, or the statistical analysis plan. It is therefore not possible to determine from this record how incomplete follow-up, treatment discontinuation, or other analysis decisions affected the results. No interim-analysis details or sample-size justification are reported.

The intervention description includes physician choice between the specified radiotherapy schedules. The record does not report how many participants received each schedule or provide an analysis by schedule. It also does not report an analysis separating the effects of Optune, bevacizumab, and irradiation. The listed adverse events should not be attributed to a specific component on the basis of this record.

The registry’s terminated status is another point of uncertainty, but the reason is not reported. It should not be interpreted as evidence of a particular safety or efficacy outcome. These limitations constrain conclusions from the registry record; they do not establish what additional information may exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Optune(NOVOTTF-100A)+ Bevacizumab+ Hypofractionated Stereotactic Irradiation Bevacizumab-Naive Recurrent Glioblastoma (GCC 1344) — NCT01925573.
• Registry record last updated 2022-02-03; status last verified 2022-01.
• Results first posted 2022-02-03.
• 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

The registry describes a single-group pilot study of Optune, bevacizumab, and hypofractionated stereotactic irradiation for bevacizumab-naive recurrent glioblastoma. Enrollment is recorded as 7; the study is listed as terminated, with a start date of 2014-05 and primary completion date of 2019-08. The reason for termination is not reported in the registry record.

The primary measure is the number of participants with a Grade 3 or higher toxicity or adverse event over 6 months. The registry record does not report its result or any statistical analyses. Adverse-event listings report 5 affected in each of the serious and other categories, selected serious-event terms with percentages, and 1 death. The record does not provide a control comparison or establish event attribution. Its results are therefore descriptive and limited.