Selinexor (KPT-330) in Combination With Temozolomide and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Selinexor (KPT-330) in Combination With Temozolomide and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma (NCT04216329), a na phase 1 study. The primary outcome is Maximum Tolerated Dose (MTD) of Selinexor.

2. Clinical Question

This was a phase I study intended to identify a tolerable dose in the setting of combined treatment, rather than to estimate a comparative treatment effect. The summary describes radiation for up to 6 weeks, temozolomide starting on the first day of radiation, and selinexor starting on the second day of radiation. It also notes that the timing of selinexor could change. The individual dose-level descriptions specify different selinexor schedules, so the dose and schedule must be considered together when interpreting the safety observations.

The registry reports enrollment of 11 participants. That small total is consistent with a dose-finding objective, but the exact dose-escalation rules and the rationale for the planned enrollment are not reported in the registry record. The primary endpoint is the maximum tolerated dose, not a measure of tumor response or survival. The posted results included in the registry record do not give a maximum tolerated dose value or the participant-level dose-limiting toxicity results needed to identify one.

3. Trial Design

The registry describes a phase I, sequential, non-masked study with allocation listed as not applicable. The intervention group is selinexor with temozolomide and radiation. There is no randomized comparator arm described, and the registry itself flags that the arms are not a like-for-like control comparison. Dose levels therefore represent stages of a dose-finding investigation, not independent treatment groups suitable for ordinary comparative-effect estimates.

Enrollment was 11, and the record states that the trial is completed. Its recorded start date is 2020-07-07 and its primary completion date is 2023-09-29. The summary says participants would be screened under another protocol, followed by neurological and physical evaluations, laboratory tests, possible brain imaging, and well-being surveys. During treatment, weekly blood tests are described. These are elements of the registry summary, not a complete account of all procedures or analysis populations.

The treatment schedule in the summary describes selinexor once weekly in weeks 1, 2, 4, and 5, alongside temozolomide and radiation. The arm descriptions, however, distinguish dose levels using other schedules: Dose Level 1 lists selinexor 80mg on weeks 1, 2, 4, 5; Dose Level 2 lists 60mg twice a week on those weeks; and Dose Level 3 lists 60mg twice a week in weeks 1-6. Readers should retain these arm-specific descriptions rather than treating the schedule as identical across dose levels.

The record does not report the escalation algorithm, rules for pausing enrollment, or a protocol-defined stopping boundary. It also does not state whether any interim safety review occurred. The sequential label alone does not establish the precise decisions made as participants entered successive dose levels. Consequently, the design can be characterized as dose-finding and sequential, but more specific operational details 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: No participants were enrolled in Dose Level -1.

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.

Population: No participants were enrolled in Dose Level -1.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of Selinexor, measured over 7 weeks.

The primary endpoint is the maximum tolerated dose of selinexor, with a listed timeframe of 7 weeks. The registry defines the MTD using dose-limiting toxicity during the period within 1 month of treatment completion. A dose meets the stated criterion when no more than 1 of up to 6 participants experiences a DLT at that dose; the dose is also described relative to a dose level at which at least 2 of 6 or fewer participants have a DLT attributed to selinexor, radiation therapy, or temozolomide.

This endpoint is used in early dose-finding studies to identify a dose level meeting a prespecified toxicity rule for a treatment combination. It is not an estimate of comparative efficacy, and the selected dose depends on the observed toxicities, their attribution, the escalation design, and the rule used to classify a DLT. The registry specifies a count-based threshold rather than reporting a continuous toxicity measure.

The posted record does not state the number of DLTs at each dose level, the dose finally selected as the MTD, or whether the stated criterion was met. Adverse-event counts alone cannot substitute for this endpoint: the registry’s serious and other adverse-event summaries do not establish which events qualified as protocol-defined DLTs or whether they occurred in the specified assessment window.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a dose-selection rule based on dose-limiting toxicities, rather than a comparison of average outcomes between randomized groups. Its interpretation requires knowing which participants were treated at each dose, which events met the DLT definition, whether each event occurred in the assessment window, and how toxicity was attributed. The registry gives a rule involving no more than 1 DLT among up to 6 participants at a dose and a higher level with at least 2 DLTs among 6 or fewer participants. The observed DLT counts and selected MTD are not reported in the registry record.

What does a sequential dose-finding design imply?

In general, a sequential design uses information accumulating during enrollment to guide which dose is studied next. That is different from assigning participants randomly among fixed treatment arms. Dose-level groups can reflect decisions made in response to earlier safety observations, and later groups may have different treatment schedules. For those reasons, differences in raw event counts across dose levels should not be treated as causal comparisons. The registry identifies the model as sequential but does not report the specific escalation algorithm, decision boundaries, or rules for replacing participants whose toxicity information is incomplete.

The record lists three dose-level schedules. Dose Level 1 is selinexor 80mg on weeks 1, 2, 4, 5 with temozolomide and radiation. Dose Level 2 is 60mg twice a week on weeks 1, 2, 4, 5 with the combination, and Dose Level 3 is 60mg twice a week in weeks 1-6. Because both dose and schedule vary, a level is not simply a higher or lower version of an otherwise identical exposure. The registry summary also describes a general schedule that differs in its wording from the arm-specific schedules. The record does not explain this discrepancy, so the arm descriptions should not be reconciled by assumption.

How should adverse-event counts be read?

Counts of participants affected are useful descriptive summaries, but they are not event rates per unit of follow-up unless the denominator and observation time support that interpretation. The registry reports participants at risk and participants affected for serious and other adverse events by dose level. Those totals do not describe event severity beyond the serious-versus-other grouping, the duration of events, recurrent events, or exposure-adjusted rates. A participant can experience more than one event, and the record does not explain whether event totals refer to people or event episodes for every summary.

In general, small groups yield imprecise estimates: a change in the experience of a single participant can substantially alter a group’s observed proportion. That general point is particularly relevant to groups with only 2 or 3 participants. It does not justify constructing additional percentages from the counts, and it does not indicate what would occur in a larger population. The registry percentages attached to selected serious-event terms should be interpreted as posted, while recognizing that the denominator and handling of overlapping terms are not reported.

What can confidence intervals and recalculations contribute?

In general, a confidence interval expresses statistical uncertainty around an estimate under a specified model and sampling assumptions. It is not a guarantee that the true value lies within the interval, nor does it account automatically for bias, missing observations, or a mismatch between the model and the design. No confidence intervals for the primary MTD result are included in the information available, and the result required to calculate or interpret such an interval is not reported.

In general, an unadjusted recalculation from posted summary statistics can help readers check arithmetic, but it cannot reproduce an adjusted sponsor analysis or recover information absent from summaries. No recalculated primary endpoint estimate is available in the record information described. If a posted sponsor analysis and a simple recalculation disagree, the sponsor’s own analysis takes precedence, as it may use participant-level information or prespecified methods unavailable in the summary. No such discrepancy is established by the registry entries stated.

The sample-size assumptions described for planning illustrations use a two-sided significance level of 0.05, equal allocation, a normal approximation, and fractions of an observed effect. In general, these calculations answer a hypothetical planning question under their assumptions; they are not observed power and do not establish that the original study was designed with those assumptions. The record does not report the original sample-size justification. Also, a dose-finding study without a randomized control comparison is not naturally interpreted through a conventional two-arm treatment-effect calculation. Any illustration should therefore remain separate from the trial’s actual dose-selection objective.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and 9 analyses. Those counts indicate that multiple outcomes and analyses are present in the record, but they do not identify how many statistical hypotheses were tested, which analyses were confirmatory, or whether any adjustment for multiple testing was used. The multiplicity strategy is not reported in the registry record. In general, testing many hypotheses can increase the chance of at least one apparently notable result by chance; adjustment methods and a prespecified hierarchy can address some of that concern, but neither is described.

The primary endpoint is defined, but its result and the DLT counts needed to evaluate it are not reported in the available record. Results for the listed secondary outcomes, including quality of life, neurocognition, and the PROMIS Depression Scale, are also not included in the registry record for this analysis. The analysis populations are not reported: it is unclear which participants were included in each outcome analysis, how participants who discontinued treatment were handled, or how missing assessments were treated.

In general, missing data can affect interpretation when the probability of missingness is related to a participant’s health, treatment exposure, or outcome. The direction and size of any resulting bias depend on why data are missing and on the analysis method. The registry information does not state the amount or pattern of missing data, any imputation approach, or sensitivity analyses. It also does not describe interim analyses, monitoring procedures, or stopping rules beyond the endpoint’s dose-limiting toxicity criterion. These details should not be inferred from the sequential design label.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: infections and infestations - other, specify: covid-19 (33.3%), fall (33.3%), muscle weakness lower limb (33.3%), muscle weakness upper limb (33.3%), encephalopathy (33.3%).

The registry reports serious and other adverse-event counts separately for each dose level. For Dose Level 1, 3 participants were at risk; 2 were reported with serious adverse events and 3 with other adverse events. For Dose Level 2, 6 were at risk; 2 were reported with serious events and 6 with other events. For Dose Level 3, 2 were at risk; none were reported with serious events and 2 with other events. These are participant counts, not comparisons adjusted for exposure or differences in follow-up.

The recorded deaths number 1, 6, and 2 across Dose Levels 1, 2, and 3, respectively. A death count does not by itself establish a treatment-related death. The record information does not give cause, timing, follow-up context, or individual attribution for these counts.

Listed serious-event terms include COVID-19 infection, falls, muscle weakness, and encephalopathy. Several terms have a reported percentage of 33.3%, and generalized muscle weakness is listed as 16.7%. The denominator for these percentages is not stated, and a participant may have experienced more than one term. These figures should be treated as descriptive registry summaries, not as evidence that each event was distinct or caused by treatment. The record does not identify which events met the protocol’s DLT definition.

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

The registry record shows that NCT04216329 was completed as a phase I sequential study enrolling 11 participants, with the goal of defining a maximum tolerated selinexor dose alongside temozolomide and radiation. It also shows serious and other adverse-event counts by dose level, and it lists selected serious-event terms. Those data describe the reported experience in the small groups enrolled.

The posted information does not report the primary MTD result, DLT counts by dose level, or the selected dose. As a result, it does not establish whether the endpoint rule was met. The adverse-event summaries cannot fill that gap because the record does not show which events qualified as DLTs, their timing within the assessment window, or their attribution under the protocol.

The dose-level figures do not establish that one schedule is safer than another. This was not a randomized comparison, the groups were small, and the schedules differed. The counts also do not establish whether treatment caused the reported events or deaths. Such conclusions would require details on causality, timing, exposure, participant characteristics, and an appropriate analysis, none of which are reported in the available information.

More generally, a maximum tolerated dose is an operational result tied to a specific toxicity definition, observation window, and dose-finding method. It is not by itself evidence about comparative benefit, long-term safety, or outcomes in populations beyond those studied. The registry summary does not provide tumor response or survival results in the registry record for this analysis. No conclusion about those outcomes should be inferred from the dose-finding design or safety counts.

The record’s completed status means the study is marked completed in the registry; it does not mean that every result needed to interpret the primary endpoint is present in the available record. Missing statistical details, including the analysis populations and handling of missing outcomes, further limit independent assessment.

13. Why This Trial Matters Statistically

This trial illustrates a statistical distinction between dose finding and comparative effectiveness. Its primary question concerns selecting a dose under a DLT rule, not estimating whether the combination performs better than an alternative. The sequential model and lack of a randomized comparator shape what can be inferred: dose-level counts are observations from a dose-finding process, not controlled estimates of treatment differences.

The endpoint’s operational definition matters. A maximum tolerated dose depends on the toxicity criterion, the number of participants evaluated at each dose, the assessment period, and the escalation decisions. Although the registry states a threshold involving participants with DLTs, the observed DLT data and final dose are not reported. Without those elements, readers cannot independently verify the main statistical objective.

The safety figures also demonstrate why denominators and context matter. The group sizes range from 2 to 6 participants, and the treatment schedules vary by dose level. Counts can describe what was recorded in those groups, but they cannot provide stable estimates of risk or support a clean ranking of schedules. Reporting follow-up, event definitions, attribution, and uncertainty would be important for interpreting safety in a dose-finding setting.

Finally, multiple listed outcomes make transparent analysis planning relevant. The record reports 10 outcomes and 9 analyses but does not report how multiplicity was handled, which outcomes were primary in analyses, or how missing assessments were managed. Those details are necessary for judging the reliability and scope of outcome claims. In this case, the available record is more informative about study structure and selected adverse-event counts than about the primary endpoint’s result.

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 most consequential limitation is that the primary endpoint result is not reported in the registry record. The DLT counts, selected MTD, and dose-level decision pathway are unavailable in the information described, preventing independent assessment of the study’s stated dose-finding objective.

Enrollment was 11, distributed across dose levels with 3, 6, and 2 participants at risk for the adverse-event summaries. These small groups yield limited precision, and the arm-specific schedules differ. The sequential, non-randomized design further means that event counts across groups should not be treated as controlled comparisons. Allocation is listed as not applicable and masking as none.

The registry summary and dose-level descriptions use different wording for selinexor scheduling. The available record does not explain that difference. It also does not report the escalation algorithm, full DLT definition beyond the endpoint summary, event attribution procedures, follow-up context for deaths, or the analysis populations. The denominator underlying selected serious-event percentages is not specified.

Multiplicity procedures, missing-data methods, interim monitoring, stopping rules, and the original sample-size rationale are not reported in the registry record. The registry lists secondary outcomes, but the outcome-specific results are not included in the information available for this analysis. These limitations restrict evaluation of both statistical precision and the completeness of outcome reporting.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Selinexor (KPT-330) in Combination With Temozolomide and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma — NCT04216329.
• Registry record last updated 2026-10-27; status last verified 2026-10.
• Results first posted 2024-10-15.
• 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

NCT04216329 is a completed phase I study sponsored by the National Cancer Institute (NCI). The registry reports a sequential, non-masked design with allocation listed as not applicable and enrollment of 11. The recorded start date is 2020-07-07, and the primary completion date is 2023-09-29.

The intervention combines selinexor with temozolomide and radiation therapy for newly diagnosed glioblastoma. The primary endpoint is maximum tolerated dose of selinexor, with a listed timeframe of 7 weeks and a DLT-based definition. The registry also lists outcomes concerning toxicity, quality of life, neurocognition, and depression.

The available safety summaries report adverse-event counts by dose level and selected serious-event terms. The primary MTD result, dose-limiting toxicity counts, and analysis details needed to evaluate that result are not reported in the registry record.