A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma (NCT01349036), a non-randomized phase 2 study. The primary outcome is Summary of Response Rates in Participants on Treatment With PLX3397.

2. Clinical Question

The study is identified as a Phase 2 investigation of orally administered PLX3397. The record describes response assessment using Response Assessment in Neuro-Oncology criteria. It defines progression-free survival from the first day of treatment to the first documented progression or death, whichever occurred first, and specifies a six-month period for the primary PFS measure. Overall survival is described as the number of participants who survived until study exit.

These definitions identify the questions the investigators intended to examine, but they do not establish what the observed response or survival outcomes were. The registry record does not report an estimated six-month PFS rate, an overall survival estimate, a confidence interval, or a statistical test for the primary outcome. The clinical question therefore remains descriptive in the available record: it documents the intended assessment of response and survival during PLX3397 treatment, without a posted numerical efficacy result.

3. Trial Design

This was a Phase 2, non-randomized, unmasked, single-group study of PLX3397 in participants with recurrent glioblastoma. The registry record lists enrollment as 38, gives a start date of 2011-12-03, a primary completion date of 2013-11-05, and a status of terminated. It does not report the reason for termination.

The record describes two cohorts with different study contexts. The surgical cohort description concerns participants requiring reoperation who would receive PLX3397 for 7 days before surgery; tissue was to be evaluated for pharmacokinetic levels and pharmacodynamic effects. The non-surgical cohort description concerns continuous oral dosing in 28 day cycles. These are not randomized treatment groups and do not provide a like-for-like control comparison. The record does not establish that differences between cohort outcomes would be attributable to PLX3397 rather than to their different clinical and study contexts.

The registry's enrollment entry and cohort descriptions should be read as separate record details, not as a basis for inferring who contributed to each analysis. In the safety information, the surgical cohort has 14 participants at risk and the non-surgical cohort has 24 participants at risk. The reason these denominators differ from the cohort descriptions is not reported in the registry record. Nor does the record explain the relationship between enrollment, cohort assignment, treatment exposure, and the analysis populations.

The primary outcome is described as response rates, with six-month progression-free survival and overall survival also specified. Response assessment was to use RANO criteria. The record states that response rates were assessed in the modified intent-to-treat population, while the adverse-event outcome refers to a safety population. It does not give further definitions of either population or report a detailed statistical analysis plan. The numerical primary outcome results and analysis estimates 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.

Before assignment: Enrollment planned to include approximately 40 participants (10 in Cohort 1 and 30 in Cohort 2) recruited from approximately 6 clinic sites.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Response rates were assessed in the modified intent-to-treat population.

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 Summary of Response Rates in Participants on Treatment With PLX3397, measured over 6 months post dose.

The primary outcome is titled as a summary of response rates among participants treated with PLX3397, with a timeframe of 6 months post dose. Its description says that response was evaluated using Response Assessment in Neuro-Oncology criteria and that participants were evaluated for progression-free survival (PFS) and overall survival (OS). The six-month PFS measure is defined as the number of participants with PFS of at least 6-month duration, with PFS measured from Cycle 1, Day 1 to the first documented progression or death, whichever came first, over a 6-month period. The description says this was evaluated using the Kaplan Meier method. OS is defined in the record as the number of participants who survived until study exit.

These outcomes address different aspects of the clinical course. Response criteria classify tumor response, while PFS concerns time until progression or death and OS concerns survival. In general, a fixed-time PFS outcome can summarize whether participants remain alive without documented progression at a specified time. A time-to-event method can also use information about when events occur and accommodate participants whose event status is not observed through the full follow-up period, subject to its assumptions.

The record provides endpoint definitions, not numerical estimates. It does not report the number meeting the six-month PFS definition, a Kaplan-Meier estimate, response counts, or an OS result. The endpoint's results and their precision are therefore not available in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group, non-randomized study with no masking. These design labels matter for interpretation. Random allocation, when used, can make treatment groups more comparable on average; this study did not use random allocation. A single-group design does not create a concurrent randomized control arm. As a result, outcome summaries can describe what happened among participants included in an analysis, but they do not isolate the treatment's effect from other explanations such as underlying disease course, participant selection, or differences in care. The record does not report a planned or external comparison that could address those limitations.

The primary outcome description uses both a response framework and survival outcomes. RANO criteria are specified for response assessment. PFS is described as time from the first treatment day until documented progression or death, whichever occurs first. The six-month PFS outcome is the number of participants with PFS of at least 6-month duration, and the record says it was evaluated using the Kaplan-Meier method. OS is described as the number of participants surviving until study exit. The registry does not provide numerical results, confidence intervals, or statistical tests for these outcomes.

General statistical explanation: Kaplan-Meier estimation is designed for time-to-event data, where participants may have different follow-up durations. A participant who has not had a recorded event by the end of observed follow-up can contribute information up to that time; that observation is commonly described as censored. The method estimates the event-free experience over time, conditional on assumptions including that censoring is not informative in a way that distorts the estimate. The registry record does not report censoring counts, follow-up distributions, or diagnostic checks, so those features cannot be evaluated from the available information.

General statistical explanation: confidence intervals express uncertainty around an estimate under a statistical model. They are useful alongside an estimate because they indicate which values are reasonably compatible with the observed data and the method's assumptions. A point estimate alone does not show its precision. No confidence interval for the primary outcome is reported in the registry record, so the precision of any response or survival estimate cannot be assessed from this information.

The record identifies the modified intent-to-treat population for response rates and a safety population for adverse events. These labels indicate that the outcome summaries may use different analysis populations. The registry does not define the membership rules for either population, report how many participants were included in the primary efficacy analysis, or explain how participants with incomplete assessments were handled. The safety risk denominators are reported separately for the two cohorts, but the record does not explain their relationship to enrollment or the cohort descriptions.

There are no analyses listed in the record. This means that no analysis-level results, model specifications, or test details are available in the information described. The registry does not report whether analyses were adjusted, how endpoint data were handled beyond the stated PFS definition, or whether any interim analyses were conducted. It also does not report a statistical analysis plan or a sample-size justification. None of these details can be inferred from the Phase 2 designation or the fact that the study was terminated.

The planning assumptions associated with sample-size illustrations are described as a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect stated as a fraction of the observed effect. The record says time-to-event illustrations use a total event count and other illustrations use participants per arm. These are planning conventions, not evidence of the study's observed power or of its original design rationale. The registry record does not report numerical illustration results in the registry record for this analysis, and no such values can be inferred from the stated assumptions alone. General statistical explanation: a sample-size calculation depends on assumptions about effect size, variability or event rate, significance level, power, allocation, and analysis method. Changing assumptions changes the planning estimate; an illustration based on an observed effect does not retroactively establish that a completed study was adequately powered.

General statistical explanation: over-dispersion matters when binary or count outcomes vary more than a simple statistical model expects. Ignoring extra variability can make uncertainty appear too small. The primary outcome in this record is described in terms of participant counts and time-to-event measures, but no over-dispersion adjustment or other model for such variability is reported. It would be inappropriate to assume that a particular model or correction was used.

Because this was a non-randomized, single-group study, general comparisons between its outcomes and outcomes in another study would also require caution. Differences in eligibility, follow-up, endpoint definitions, participant characteristics, and care can affect cross-study comparisons. The registry record does not provide a prespecified external comparator or details that would support an adjusted comparative analysis. The available information is therefore best read as a record of the study design and selected outcome definitions, rather than a complete inferential analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome description involving response rates, PFS, and OS, and lists six outcome measures overall. It does not report a statistical analysis plan, the ordering of tests, or any adjustment for multiple comparisons. It is therefore not possible to determine from the registry record how multiplicity was handled, whether particular outcomes were considered confirmatory, or whether any reported significance level was adjusted for multiple testing. No primary-outcome test results are reported.

The response population is identified as modified intent-to-treat, and the safety outcome refers to a safety population. The record does not define who qualified for these populations or provide a participant flow showing inclusion in each analysis. It does not report how missing response assessments, incomplete follow-up, or other unavailable outcome data were treated. Although the PFS definition specifies progression or death as events and identifies Kaplan-Meier evaluation, the record does not give details about censoring decisions or the handling of participants whose status was not known at the end of observation.

The registry reports an enrollment of 38, while safety denominators are listed by cohort. It also gives cohort descriptions that do not directly match those safety denominators. The reasons for these differences, and whether they reflect eligibility, exposure, analysis inclusion, or another factor, are not reported in the registry record. These details matter because analysis populations and missing-data handling can affect both the interpretation and precision of outcome estimates.

The study status is terminated, but the record does not report why. It also does not state whether termination changed planned analyses, follow-up, or the availability of outcome data. No conclusion about the presence or direction of bias from missing data or multiplicity can be drawn from the available record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: convulsion (21.4%), pneumonia (14.3%), dysarthria (7.1%), meningitis (7.1%), hypertension (7.1%).

The registry reports serious adverse event summaries separately for the two cohorts. For the surgical cohort, 8 participants were affected among 14 at risk, and the number at risk for other serious events is also 14. For the non-surgical cohort, 11 participants were affected among 24 at risk, with 24 at risk for other serious events. The record lists 0 deaths for the surgical cohort and 1 for the non-surgical cohort. These figures are counts, not a randomized comparison of treatment strategies.

The most frequently listed serious-event terms are convulsion at 21.4% and pneumonia at 14.3%. Dysarthria, meningitis, hypertension, and thrombosis are each listed at 7.1%. These are registry-reported term percentages. The record does not provide enough detail to determine from these figures alone how events were classified, whether a participant could contribute more than one event term, or whether the listed serious events were judged related to study drug.

In general, a serious adverse event is a safety category, while an adverse event being related to treatment is a separate attribution judgment. Occurrence during a study does not establish causation. These counts also do not account, on their own, for differences in follow-up or participant characteristics between cohorts. The record's cohort descriptions differ in their study context, and allocation was not randomized. The serious-event information is therefore descriptive; it does not establish comparative risk or a causal effect of PLX3397.

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

The registry record shows that PLX3397 was studied in participants with recurrent glioblastoma in a Phase 2, non-randomized, single-group, unmasked study. It records an enrollment of 38 and describes a surgical cohort and a non-surgical cohort. It also specifies response, PFS, and OS as outcomes of interest and provides definitions for the primary outcome assessment. The record's status is terminated.

What the posted information does not show is the numerical primary outcome result. It does not report the response count, six-month PFS estimate, OS estimate, or uncertainty intervals for these outcomes. Without those results, readers cannot assess the size or precision of an observed response or survival outcome from this record. The endpoint definitions describe what was intended to be measured; they are not themselves evidence of a particular outcome.

The design does not include a randomized comparator. Any outcome observed among participants treated in a single group would be descriptive and could not, by itself, distinguish treatment effects from other explanations. Nor should the surgical and non-surgical cohorts be treated as though one were a control group for the other. Their study contexts differ, and they were not randomized to those cohorts.

The safety counts give information about serious adverse events reported by cohort, but do not establish that PLX3397 caused the events or allow a controlled comparison of risk. The registry does not state why the study was terminated, how missing outcome data were handled, or how participants were selected for the different analysis populations. Those unknowns limit what can be concluded from the available record.

Accordingly, the statistically supported reading is narrow: the record describes a clinical study design, planned outcome definitions, and selected safety counts, but does not provide numerical primary efficacy results or a controlled estimate of treatment effect. No medical recommendation follows from these registry entries.

13. Why This Trial Matters Statistically

This study illustrates why design information and outcome results need to be read together. A Phase 2 label and a clearly described endpoint do not, by themselves, supply evidence about the observed response or its precision. Here, the registry defines response assessment and describes six-month PFS and OS, but does not report their numerical results. The distinction between a planned measure and a reported estimate is central to statistical interpretation.

The non-randomized, single-group structure also highlights the difference between describing outcomes and estimating a comparative treatment effect. A single-group study can document outcomes among the participants included in its analyses. Without a randomized control group, however, those observations do not establish what would have happened under an alternative treatment or without the study treatment. The two cohort descriptions cannot fill that role because they concern different study contexts and were not randomized.

The record also demonstrates why analysis populations and denominators deserve attention. It identifies a modified intent-to-treat population for response and a safety population for adverse events, but does not define either. Cohort safety denominators are reported, while their relationship to the cohort descriptions and enrollment is not explained. Such distinctions affect which participants an estimate describes and how it should be interpreted.

Finally, reporting precision matters as much as reporting an outcome definition. Without an estimate and confidence interval, readers cannot judge the uncertainty in the primary outcome. Without a reported analysis plan or missing-data account, readers also cannot assess several important features of the analysis. These are general considerations for interpreting clinical trial records, and they are especially relevant when the available record is descriptive and lacks primary outcome estimates.

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 record is limited by the absence of numerical primary efficacy results. Although it defines response, PFS, and OS outcomes, it does not report response counts, a six-month PFS estimate, an OS estimate, confidence intervals, or outcome-specific tests. Consequently, neither the magnitude nor precision of the primary outcome can be evaluated from the registry record.

The study's single-group, non-randomized design provides no randomized comparator. The surgical and non-surgical cohorts have different descriptions and cannot be treated as interchangeable treatment groups or as a control comparison. The study was unmasked, and the record does not report other procedures for limiting assessment bias. These design features constrain causal interpretation.

There are also unresolved differences among the record's population descriptions. Enrollment is listed as 38; the cohort descriptions state 10 and 30 participants, while the safety at-risk counts are 14 and 24. The registry record does not explain how these figures relate to one another, how the modified intent-to-treat and safety populations were formed, or how many participants contributed to each primary outcome analysis.

The record does not report missing-data methods, detailed follow-up information, the statistical analysis plan, multiplicity procedures, or a sample-size justification. It gives the study status as terminated but does not report the reason or its consequences for analysis and follow-up. The available safety summaries are also descriptive and do not establish event causation or comparative risk. These omissions prevent a fuller assessment of the study's statistical conduct and interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma — NCT01349036.
• Registry record last updated 2020-03-03; status last verified 2020-02.
• Results first posted 2020-01-09.
• 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

NCT01349036 is a Phase 2 study of PLX3397 in recurrent glioblastoma. The registry describes it as non-randomized, unmasked, and single group, with enrollment listed as 38. The study started on 2011-12-03, had a primary completion date of 2013-11-05, and is recorded as terminated; the reason for termination is not reported in the registry record.

The primary outcome description concerns response rates, including six-month PFS and OS, and names RANO criteria and Kaplan-Meier evaluation. Numerical primary outcome results and their precision are not reported. Safety information includes serious adverse event counts by cohort, but it is descriptive and does not establish causation or a randomized comparison. Definitions of analysis populations, missing-data handling, and detailed statistical methods are not reported in the registry record.