Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma (NCT00795665), a na phase 2 study. The primary outcome is Progression-free Survival.

2. Clinical Question

The clinical question was whether progression-free survival could be characterized among patients receiving the combination. The outcome definition uses progression criteria based on RECIST version 1.0: an increase in the summed longest diameters of target lesions, measurable growth in a non-target lesion, or new lesions. Death from any cause also counted as an event.

The registry describes the study as a phase II trial of bevacizumab and carmustine for relapsed or progressive high-grade glioma. It also lists radiographic response, the distinction between response due to tumor shrinkage and response due to reduced vasogenic edema, safety and toxicity, and overall survival as secondary outcomes. Results for those outcomes are not reported in the registry record.

This is a description of a treatment group, not an estimate of the difference between two treatments. Without a concurrent comparator, the record cannot establish how outcomes under the combination compare with outcomes under another treatment or under no study treatment. Further, the primary outcome has no reportable results in the registry, so the record does not answer the progression-free survival question with an estimated outcome.

3. Trial Design

The registry identifies NCT00795665 as a phase II study of bevacizumab and carmustine in patients with relapsed or progressive high-grade glioma. The listed study title describes treatment with the two drugs, and the official title identifies the study as a phase II study of bevacizumab and BCNU, another name used in the title for carmustine.

The design is recorded as single-group. Allocation is listed as not applicable, and masking is listed as none. The registry therefore does not describe random assignment or a masked comparison. The arm is named Bevacizumab and Carmustine; no separate control arm is recorded. The listed enrollment is 7.

The study status is completed. The registry records a start date of 2008-06 and a primary completion date of 2015-12. These dates describe the study record and do not establish how long each participant was followed. The primary outcome timeframe is stated as time from the first treatment day to progression or death from any cause, up to 7 years.

Several design details that would help interpret the treatment course are not reported in the registry record, including drug doses, administration schedules, eligibility criteria beyond the disease description, follow-up visit schedule, and the number of participants contributing data to each outcome. The registry also does not report a protocol-level statistical plan or a sample-size justification. The planning assumptions associated with sample-size illustrations are not the same as evidence that the trial was designed to achieve a particular power.

Because the study has one treatment group and only 7 enrolled participants, its design is descriptive rather than a like-for-like controlled comparison. The record can describe the registered intervention, outcome definitions, and reported safety counts. It cannot separate treatment-associated outcomes from other explanations using a randomized control comparison. Most importantly, the registry reports that the imaging procedure needed for the planned volumetric analysis could not be performed, and no primary outcome data can be reported.

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

Analysis population for the primary outcome, as defined in the registry: Procedure for fusing PET and MRI images could not be performed; as such the volumetrics of areas of tumor versus cerebral edema could not be analyzed or interpreted, therefore, no data can be reported.

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 Progression-free Survival, measured over Time from first day of treatment to the first observation of disease progression or death due to any cause (up to 7 years)..

Progression-free survival is the primary endpoint. It measures the time from the first day of treatment until the first recorded disease progression or death from any cause. The registry specifies that the timeframe was up to 7 years. The progression definition follows RECIST version 1.0: progression could be based on an increase in the summed longest diameters of target lesions, measurable growth in a non-target lesion, or the appearance of new lesions.

As a general statistical concept, a time-to-event endpoint uses both whether an event occurs and when it occurs. This can be useful when participants have different lengths of observation, because the timing of progression or death is part of the outcome rather than a simple yes-or-no status at one visit. Interpretation depends on clearly defining the event, follow-up, and how observations without a recorded event are handled. Those analysis details are not reported in the registry record.

The endpoint has no reported result in the registry. The registry explains that the procedure for fusing PET and MRI images could not be performed; consequently, the volumetrics of tumor areas versus cerebral edema could not be analyzed or interpreted, and no data can be reported. This prevents a numerical summary of the primary endpoint from being interpreted from the record. The intended timeframe is not evidence that every participant was followed for that duration, and the registry does not report individual follow-up or event times.

Radiographic response and overall survival are listed as secondary outcomes, along with safety and toxicity and assessment of whether a radiographic response reflected tumor shrinkage or reduced vasogenic edema. Their results are not reported in the registry record either. Thus, the endpoint definition is available, but an estimate of progression-free survival or its precision is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Progression-free survival is a time-to-event outcome. As a general statistical concept, each participant contributes information about the time from a defined starting point until an event, with progression or death serving as the event in this study. The registry sets the starting point at the first day of treatment and defines progression using RECIST version 1.0. It does not report how follow-up ended for participants without a recorded event or how such observations were handled analytically.

What does the endpoint definition establish?

The definition identifies which clinical events were intended to count. Progression could be an increase in the sum of the longest diameters of target lesions, measurable increase in a non-target lesion, or appearance of new lesions. Death from any cause was also included in the primary endpoint. A clear event definition is important because changing what qualifies as progression can change when an event is considered to have occurred.

However, an endpoint definition is not an endpoint result. The registry does not provide event counts or event times for progression-free survival. It reports that PET and MRI image fusion could not be performed, so tumor-versus-edema volumetrics could not be analyzed or interpreted, and no data can be reported. The record does not explain how this technical limitation affected every component of the endpoint assessment, so its full effect on the analysis cannot be determined from the registry.

How should time-to-event estimates be understood?

In general, time-to-event methods can use partial follow-up when a participant has not had an event by the last observation. Such observations are often described as censored, meaning that the event time is not observed within the available follow-up. Valid interpretation depends on how censoring is defined and on assumptions about the relationship between follow-up and the event process. The registry record does not report censoring rules, a time-to-event estimator, or related assumptions for this study.

A confidence interval, as a general statistical concept, gives a range of values compatible with the data under a specified method and its assumptions. It communicates uncertainty around an estimate, not the probability that a treatment is effective. No progression-free survival estimate or confidence interval is reported in the registry, so neither the outcome level nor its statistical precision can be assessed.

What does the single-group structure mean?

The study is recorded as single-group, with allocation not applicable and no masking. There is no concurrent control group in the registry record. As a general principle, a one-group outcome can describe the participants studied but cannot, by itself, provide a randomized estimate of the difference between the study treatment and a comparator. This distinction remains important even when outcome data are available; in this record, the primary outcome data are not reported.

The enrollment of 7 is the total listed for the study. The registry does not state the number contributing to each outcome, the number with complete imaging, or an analysis population definition. Those details matter because the enrolled cohort and the set included in a particular analysis may differ. No intention-to-treat, per-protocol, or other analysis population is specified in the registry record.

How should planning calculations be read?

The stated sample-size assumptions describe planning illustrations, not the original trial's design justification. They use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. Time-to-event illustrations give the total number of events using the Schoenfeld approach, while other illustrations give participants per arm. These are conventions for the planning illustrations and do not change the fact that the registered study is single-group.

As a general concept, a significance level is a threshold used in a specified hypothesis-testing procedure. It does not measure the probability that a finding is true, and it does not guarantee that a study will detect an effect. Equal allocation between two arms is a calculation assumption here, not a description of this trial's allocation. The registry does not report that the trial used those assumptions to set its enrollment target, and its record does not include a sample-size justification.

Planning calculations based on an observed effect should not be interpreted as observed power. Observed power is not a substitute for reporting the estimated outcome and its uncertainty. In this case, the primary endpoint result is absent from the registry record, so readers cannot connect the planning illustration to an outcome estimate for progression-free survival. The calculations also cannot turn a single-group study into a two-arm comparison.

What analysis details remain unknown?

The registry records zero analyses. It does not report a statistical model, adjustment variables, significance tests, confidence intervals, missing-data procedures, interim analyses, or a multiplicity strategy. These details are not inferable from the endpoint definition or the study phase. No protocol-specific analysis plan is reported in the registry record.

In general, analysis choices should follow the outcome structure and study design. For a time-to-event endpoint, methods need to address event definitions, duration of observation, and observations without an event. For multiple outcomes or repeated tests, the interpretation of nominal statistical evidence can depend on whether and how multiplicity is handled. These are general methodological considerations, not claims about analyses conducted in this study.

The registry's stated imaging problem is especially consequential for interpreting the primary endpoint information. It prevents the planned separation of tumor volume from cerebral edema, and the record says no data can be reported. The record does not provide an alternate analysis, a sensitivity analysis, or a description of any substitute measurement. Consequently, statistical methods cannot recover a result that the registry does not report.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies progression-free survival as the primary outcome and lists radiographic response, differentiation of response due to tumor shrinkage versus reduced vasogenic edema, safety and toxicity, and overall survival as secondary outcomes. It does not report a multiplicity plan. The registry record does not say whether hypotheses were tested in a prespecified order, whether significance levels were adjusted, or whether any secondary outcomes were treated as exploratory.

As a general statistical principle, when multiple outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase if each is assessed independently. Adjustment strategies or a prespecified hierarchy can help define how evidence is interpreted. This is a general concern and does not imply that any particular procedure was used in this study.

The registry reports that the PET and MRI image-fusion procedure could not be performed, preventing the volumetric analysis of tumor areas versus cerebral edema. It states that no data can be reported. The record does not describe whether this represents missing measurements for some or all participants, whether another measurement was available, or whether any missing-data method was used. The effect of the technical problem on the analysis cannot be reconstructed from the record.

Analysis populations are also not specified. The registry does not report whether results were based on all enrolled participants, participants who began treatment, participants with evaluable imaging, or another group. It gives no outcome-specific denominators. Thus, the enrollment of 7 should not be assumed to be the denominator for every endpoint.

No imputation method, complete-case procedure, sensitivity analysis, interim analysis, or statistical analysis plan is reported in the registry record. These omissions limit assessment of how missing outcome information and multiple outcomes were handled. The absence of such details should not be filled by assuming a conventional approach.

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 non-serious adverse event terms

The registry's safety fields report 0 participants affected by serious adverse events among 7 at risk in the Bevacizumab and Carmustine group. It reports 7 participants affected by other adverse events among 7 at risk. The registry count for deaths is 0. No serious adverse event terms are listed.

These are registry counts, not a detailed description of event types, timing, severity grades, duration, or relationship to study treatment. The distinction between the serious adverse event count and the other adverse event count should be retained; the registry does not provide enough detail to infer what the reported other events were. It also does not report exposure duration or outcome-specific follow-up, so the counts should not be converted into rates over time.

A count of 0 serious adverse events in this small enrolled group does not establish that serious events cannot occur, nor does the other adverse event count establish a causal relationship to either drug. The record reports the figures but does not provide a comparative safety analysis. There is no control group in the registered design, and the registry does not report additional statistical analyses of these safety data.

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

The record documents a completed phase II, single-group study of bevacizumab and carmustine in relapsed or progressive high-grade glioma, with 7 participants enrolled. It defines progression-free survival and the criteria intended to identify progression. It also records serious and other adverse event counts. These registry entries describe the registered study and its available registry results; they do not constitute an estimate of treatment benefit.

The most important limit is the absence of reportable primary outcome data. The registry states that PET and MRI image fusion could not be performed, preventing analysis or interpretation of the tumor-versus-edema volumetrics, and therefore no data can be reported. No progression-free survival estimate, event count, confidence interval, or time-to-event analysis is included. The record therefore cannot show the observed progression-free survival pattern or how precisely it was estimated.

The absence of a primary outcome result should not be interpreted as a result of no progression, no deaths, or no difference. Those conclusions are not reported. Nor does the record establish that the intervention did or did not change outcomes. The study has no concurrent comparator, so even a reported outcome in the treatment group would not provide a randomized treatment contrast.

The registry lists secondary outcomes, but does not report their results. Their inclusion in the record's outcome list is not evidence that a response, survival, or safety analysis was completed. Safety counts can be described as reported, but they do not establish treatment causation or comparative risk.

For readers, the appropriate interpretation is bounded: the registry describes the design, endpoint definition, enrollment, and certain safety counts, while the primary outcome data are unavailable in the record. Any conclusion about the magnitude, direction, or precision of a treatment effect would go beyond the reported information. The registry also does not provide the full protocol or analysis methods needed to resolve remaining design and analysis questions.

13. Why This Trial Matters Statistically

This study is statistically notable because it illustrates the difference between an endpoint being defined and an endpoint result being available. Progression-free survival has a stated start point, event definition, and timeframe, but the registry reports no data for it after a technical imaging limitation prevented the planned volumetric analysis. Without outcome estimates, readers cannot assess the result's magnitude or precision.

The single-group design is another important feature. It can describe an enrolled treatment group, but it does not create a randomized contrast with another treatment. This matters when interpreting any observed outcome, because a descriptive result and a comparative treatment estimate answer different questions. In this record, no primary outcome estimate is available for even a descriptive progression-free survival summary.

The enrollment of 7 also highlights why denominators and uncertainty matter. Small studies may be useful for describing feasibility or generating questions, but estimates from small cohorts can be unstable in general. The registry does not provide endpoint estimates or intervals, so the potential uncertainty cannot be quantified for this study's primary outcome.

Finally, the record distinguishes planning assumptions from actual trial results. Planning illustrations based on an observed effect are not evidence of observed power, and assumptions for equal allocation across two arms do not describe this single-group design. Keeping design, planning, and analysis separate prevents a calculation convention from being mistaken for a feature of the trial or an outcome finding.

Together, these points show why a careful registry reading should attend to the outcome actually reported, the study's comparison structure, and the availability of analysis details. Here, the endpoint definition is informative, but the absence of reportable primary outcome data sharply limits what can be concluded statistically.

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.

The primary limitation is specific to the endpoint measurement: the registry says the procedure for fusing PET and MRI images could not be performed. As a result, tumor areas and cerebral edema could not be separated through the planned volumetric analysis, and no data can be reported. The registry does not explain whether an alternative assessment was attempted or whether another analysis could address the issue.

The cohort is small, with 7 participants enrolled, and the study is single-group. There is no concurrent control arm in the record, so comparative treatment effects cannot be estimated from this design. The registry also does not give outcome-specific denominators, event counts, follow-up summaries, or analysis populations.

Although the primary outcome timeframe extends up to 7 years, individual follow-up durations and censoring details are not reported. The timeframe alone does not show that all participants were observed for the full period. The record does not provide a statistical analysis plan, missing-data method, multiplicity approach, interim analysis information, or sample-size justification.

The listed secondary outcomes do not have reported results in the registry. Safety information is limited to event counts and does not include event terms, timing, severity detail, exposure duration, or a comparison group. These gaps prevent a detailed assessment of the broader outcome profile.

These limitations are limitations of what the registry record reports. They do not establish what may have been measured or analyzed outside the record, and those unreported details cannot be inferred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma — NCT00795665.
• Registry record last updated 2020-05-12; status last verified 2020-05.
• Results first posted 2020-05-12.
• 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

NCT00795665 is a completed phase II, single-group study of bevacizumab and carmustine for relapsed or progressive high-grade glioma. The registry lists enrollment of 7, no masking, and no separate comparator. The recorded start date is 2008-06 and the primary completion date is 2015-12.

The primary outcome is progression-free survival, defined from the first treatment day to progression or death from any cause, with progression criteria based on RECIST version 1.0. The registry reports that PET and MRI image fusion could not be performed, so tumor-versus-edema volumetrics could not be analyzed or interpreted and no data can be reported. No primary outcome analysis result is included.

Safety counts list 0 participants with serious adverse events among 7 at risk, 7 with other adverse events among 7 at risk, and 0 deaths. Serious adverse event terms are not listed. Secondary outcomes include radiographic response, response differentiation, safety and toxicity, and overall survival, but their results are not reported in the registry record.