Dasatinib in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dasatinib in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma (NCT00423735), a na phase 2 study. The primary outcome is Number of Patients Achieving 6-month Progression-free Survival (6mPFS).

2. Clinical Question

The trial is titled “Dasatinib in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma,” and its official title describes a phase II trial of dasatinib in patients with recurrent glioblastoma multiforme. Its stated purpose was to study how well dasatinib works in this setting. The registry rationale says dasatinib may stop tumor-cell growth by blocking some enzymes needed for cell growth; that rationale is not itself evidence of a clinical outcome.

The primary question is about the proportion of treated eligible patients who meet a time-specific status, rather than change in a continuous measurement. A patient must be alive and without progression at the specified assessment to count toward 6-month progression-free survival. The registry describes the population as eligible patients who started protocol treatment. It does not report the observed number meeting that endpoint, so the result of the primary question cannot be determined from the registry record.

3. Trial Design

This was a phase II, single-group, unmasked study sponsored by the National Cancer Institute (NCI). The registry records enrollment of 64 and a completed status. The recorded start date is 2007-01-24, and the primary completion date is 2011-03-09. The registry does not describe a randomized allocation or a concurrent control group.

Patients received dasatinib by mouth twice daily on days 1-28. Courses were to repeat every 28 days unless disease progression or unacceptable toxicity occurred. A pharmacological study was also listed. The registry’s primary endpoint description refers to a two-stage phase II design, labeled Stage 1B and 2. It states that the primary endpoint would be assessed among patients combined from those stages if the study continued to Stage 2. Separate safety groups are labeled Stage 1: Dasatinib 200mg/Day and Stage 1B: Dasatinib up to 400mg/Day. These labels describe dose stages, not randomized treatment arms with a control group.

The design description gives a null hypothesis of 11% and an alternative hypothesis of 25% for 6-month progression-free survival. It identifies Simon's minmax 2-stage design and states that type I and type II error were both set at 10%. The first-stage decision was intended to determine whether accrual continued; the exact continuation criterion is not reported in the registry record. After Stage 2 accrual and 6 months of follow-up, the specified rule was to reject the null hypothesis in favor of the alternative if 9 or more patients were alive without progression at 6 months.

The record does not report the actual stage-by-stage accrual, whether the study proceeded through all planned stages, or the observed primary endpoint count. The listed enrollment does not by itself establish which patients entered a particular dose stage or contributed to the primary analysis.

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: Per protocol criteria, the study did not continue to Stage 2 and therefore no patients were accrued to this arm.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Eligible patients who started protocol treatment.

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: Eligible patients who started protocol treatment.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients Achieving 6-month Progression-free Survival (6mPFS), measured over Registration to 6 months.

The primary endpoint is the number of patients achieving 6-month progression-free survival (6mPFS), measured from registration to 6 months. The registry defines the relevant status as alive without progression at 6 months. The stated analysis population is eligible patients who started protocol treatment.

This endpoint combines two clinically relevant aspects of a patient’s status at a specified time: whether the patient is alive and whether disease progression has occurred. It is a binary outcome for each patient—meeting the endpoint or not—and the reported primary measure is a count of patients meeting it. In general, a fixed-time progression-free survival endpoint can be used to assess whether a treatment merits further study in a phase II setting, while avoiding the implication that every patient has the same follow-up duration beyond the assessment point.

The registry’s design compares the planned endpoint rate with a null hypothesis of 11% and an alternative hypothesis of 25%. Those values are design assumptions, not observed results. The stated rule requires 9 or more patients to be alive without progression by 6 months after Stage 2 accrual and follow-up are complete to reject the null in favor of the alternative. The record does not report whether that rule was met or the observed endpoint count. It also does not report a confidence interval or other estimate of uncertainty for the actual 6mPFS result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical plan described in the registry is a two-stage phase II design. Stage 1B and Stage 2 patients would be combined for the primary endpoint if the study continued to Stage 2. The design’s purpose is to make an early decision about whether further accrual is warranted, then assess the endpoint using the planned rule after later accrual and follow-up. The exact first-stage continuation criterion is not reported in the registry record.

What the hypotheses mean

The null hypothesis is stated as 11%, and the alternative hypothesis as 25%, for 6-month progression-free survival. In general, the null is the reference rate the design is set up to challenge; the alternative is the rate the study is designed to distinguish from that reference. These are planning hypotheses, not estimates of what occurred in the trial. The registry says Simon's minmax 2-stage design was used and that type I and type II error were both set at 10%.

In general, type I error is the chance of rejecting a null hypothesis when it is true under the assumptions of a statistical design. Type II error is the chance of failing to reject the null under the alternative specified for planning. These design properties describe the planned decision procedure, not the probability that the observed conclusion is correct. Their interpretation depends on the design assumptions and on carrying out the specified analysis.

How the decision rule works

The registry states that if the first stage met its criteria, accrual would continue; otherwise, there would be no further accrual and the alternative hypothesis would be rejected. The first-stage criterion is not reported in the registry record. For the later assessment, the registry specifies that after Stage 2 accrual completion and 6 months of follow-up, 9 or more patients alive without progression by 6 months would lead to rejection of the null hypothesis in favor of the alternative. This is a planned threshold. The registry does not report the observed count or whether the threshold was reached.

A two-stage design uses an interim decision point as part of its planned structure. In general, early stopping can avoid continuing a study when the observed results do not satisfy the continuation rule. That feature does not mean that an interim analysis was actually performed as intended: the record does not report stage-specific accrual or whether the study proceeded to Stage 2.

What a confidence interval would add

In general, a confidence interval expresses uncertainty around an estimated quantity, such as a proportion. A narrower interval indicates greater precision under the method’s assumptions, while a wider interval indicates more uncertainty. The registry record does not report an observed primary endpoint estimate or a confidence interval, so the precision of the endpoint result cannot be assessed from this record.

The endpoint is binary at the patient level: a patient either meets the specified 6-month status or does not. The registry’s primary measure is the number achieving that status. Interpreting a count requires knowing the analysis population and how missing or unevaluable endpoint status was handled. The stated population is eligible patients who started protocol treatment, but the missing-data handling and actual analysis denominator are not reported in the registry record.

Why the design is not a comparative trial

The study is identified as single-group, unmasked, and with allocation not applicable. In general, a randomized control group helps distinguish treatment-related differences from differences arising from patient characteristics, time trends, or other factors. This design does not offer that randomized comparison. The Stage 1 and Stage 1B dose groups are not described as randomized, and the registry explicitly does not support treating the arms as a like-for-like control comparison.

Accordingly, the trial’s planned statistical decision concerns whether the single-group endpoint result crosses a prespecified benchmark, not whether dasatinib outperforms a concurrent control. Even if the observed endpoint result were available, a one-group design would require cautious interpretation about causation. In this record, the missing endpoint result makes even the planned benchmark decision unavailable.

Other outcomes and analyses

The registry lists several secondary outcomes, including overall survival, response rates at six months, progression-free survival, adverse-event rate, molecular-marker correlations, and pharmacokinetic correlations. In general, examining several outcomes raises a multiplicity question: when multiple statistical tests are conducted, the chance of at least one apparently notable result can increase. The registry record does not report a multiplicity adjustment or describe how these secondary analyses were to be interpreted together.

The record lists one analysis, but it does not provide a detailed statistical analysis plan, the methods for estimating secondary outcomes, or the results of those analyses. It also does not report whether analyses were prespecified beyond the primary design description. The registry does not describe covariate adjustment, subgroup analyses, model diagnostics, or sensitivity analyses. These methods should not be inferred from the general description of a phase II design.

In general, a sample-size calculation is a planning tool based on assumptions about the endpoint, design, and desired operating characteristics. It is not an observed outcome and cannot show that a study had a particular level of power after results are known. The registry gives the two-stage design assumptions for the primary endpoint, but a separate sample-size justification beyond those details is not reported in the registry record.

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("Stage 1: Dasatinib 200mg/Day", "Stage 1B: Dasatinib up to 400mg/Day")
n      <- c(21, 29)
events <- c(1, 2)
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  Stage 1: Dasatinib 200mg/Day  21  1  4.8  0.1  23.8  0.8  22.7  1.1  22.8
ARM  Stage 1B: Dasatinib up to 400mg/Day  29  2  6.9  0.8  22.8  1.9  22.0  2.1  22.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes alongside the primary 6-month progression-free survival endpoint. They include overall survival, treatment response rates at six months, progression-free survival, adverse-event rate, molecular-marker correlations, and pharmacokinetic correlations. The record does not report an adjustment for multiple testing or a hierarchy specifying how secondary outcomes should be interpreted relative to one another. In general, when several outcomes are examined, the chance of observing at least one apparently notable finding can increase; a prespecified approach can help control or contextualize that issue.

The registry describes the primary population as eligible patients who started protocol treatment. It does not report the actual number included in the primary endpoint analysis, the number with evaluable 6-month status, or the handling of missing endpoint data. It is therefore not possible to determine from this record whether missing observations were excluded, treated as failures, or handled by another method. No imputation or sensitivity-analysis approach is reported in the registry record.

The registry does not provide detailed analysis populations for the secondary outcomes, nor does it say whether the safety summaries use all treated patients or another defined group. The description of two-stage accrual does not supply stage-specific analysis counts. The record also does not report a full statistical analysis plan, such as prespecified subgroup methods, adjustment variables, or rules for incomplete follow-up. These omissions limit reproducibility and make it difficult to assess how closely the observed analyses, if available elsewhere, would correspond to the planned methods.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: disease progression nos (13.8%), convulsions nos (10.3%), dehydration (9.5%), anorexia (6.9%), headache (6.9%).

The registry reports two safety groups: Stage 1: Dasatinib 200mg/Day and Stage 1B: Dasatinib up to 400mg/Day. In the first group, 21 participants were at risk for serious adverse events and 8 were recorded as affected; 21 were at risk for other adverse events and 21 were recorded as affected. In the Stage 1B group, 29 participants were at risk for serious adverse events and 14 were recorded as affected; 29 were at risk for other adverse events and 23 were recorded as affected.

These are descriptive counts within the registry’s labeled groups. The groups are dose stages, not randomized comparison arms, and their counts should not be interpreted as a controlled comparison of safety. The record does not report detailed event-level information such as timing, duration, recurrence, severity grading beyond the serious-event category, or attribution to treatment for each event.

Selected serious adverse-event terms are listed with percentages: Disease progression NOS, 13.8%; Convulsions NOS, 10.3%; Dehydration, 9.5%; Anorexia, 6.9%; Headache, 6.9%; and Peripheral motor neuropathy, 6.9%. The registry does not state the denominator or provide enough detail to infer how these percentages relate to the two dose-stage groups. They should be read as listed serious-event summaries, not as a complete account of all adverse events or as a comparative risk estimate.

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

The registry establishes that a phase II, single-group study of dasatinib was conducted for recurrent glioblastoma multiforme or gliosarcoma and was marked completed. It also records a planned primary endpoint, a two-stage decision framework, the intervention schedule, and selected safety summaries. Those details explain what the study set out to assess and how its primary decision was intended to be made.

The record does not report the observed number of patients achieving 6-month progression-free survival, whether the design’s threshold of 9 or more was met, or a corresponding estimate of uncertainty. It therefore does not show whether the primary endpoint met the planned criterion. The stated null hypothesis of 11% and alternative hypothesis of 25% are design assumptions, not trial results. Completion status is not a substitute for a reported endpoint analysis.

The trial’s single-group design also means it was not set up as a randomized comparison with a control group. The registry’s dose-stage labels do not create such a comparison. In general, evidence from a single group can describe outcomes among treated participants, but it cannot by itself separate treatment effects from other explanations for those outcomes. Here, the missing primary endpoint result further restricts what can be said about the observed clinical course.

The listed secondary outcomes and safety terms should likewise not be mistaken for reported efficacy findings or a complete assessment of harms. The record names outcomes of interest but does not provide their results. Selected serious adverse-event counts and percentages describe registry entries; they do not establish comparative safety or the overall balance of benefit and risk.

The defensible conclusion is about the study’s design and reporting: the registry describes a planned phase II endpoint test and selected adverse-event summaries, but the primary outcome result and several details needed to interpret it are not reported in the registry record. No conclusion that dasatinib did or did not meet the endpoint criterion is supported by the information recorded.

14. Why This Trial Matters Statistically

This trial illustrates how a phase II study can use a prespecified benchmark and a staged design to structure an early decision. The registry names a null hypothesis of 11%, an alternative hypothesis of 25%, and a rule requiring 9 or more patients alive without progression at 6 months after Stage 2 accrual and follow-up. Those design elements make the intended decision framework explicit, even though the observed result is not reported.

It also highlights the importance of distinguishing a planned design from a reported finding. A completed status does not reveal whether the first-stage continuation criterion was met, whether Stage 2 was completed, or whether the primary endpoint threshold was reached. Without the outcome count and analysis denominator, the primary decision cannot be reconstructed from the registry record.

The single-group structure is another important statistical feature. A single-group phase II study can be organized around whether an outcome rate appears promising relative to a benchmark, but it does not provide a randomized control comparison. The separate dose-stage labels should not be mistaken for such a comparison. This distinction matters when readers consider whether an outcome, if reported, could be attributed to treatment.

Finally, the record demonstrates why outcome definitions, analysis populations, missing-data methods, and uncertainty estimates matter. It defines the population and endpoint in broad terms, but does not report the actual endpoint result, its precision, or the handling of missing status. The listed secondary outcomes and safety summaries cannot fill that gap. Statistical interpretation depends not only on the planned decision rule, but also on complete reporting of the data and analysis to which that rule was applied.

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 most important limitation for interpreting this registry record is that the observed primary endpoint result is not reported. The record does not state how many eligible patients who started treatment were alive without progression at 6 months, whether the planned decision threshold was reached, or the precision of any endpoint estimate. Although enrollment is recorded as 64, the number included in the primary analysis and the endpoint denominator are not reported in the registry record.

The design information is incomplete for reconstructing trial conduct. The primary endpoint description refers to Stage 1B and 2, while safety groups are labeled Stage 1 and Stage 1B. The record does not explain the relationship between these labels, report stage-specific accrual, or state whether the study proceeded through all planned stages. The exact first-stage continuation criterion is not reported in the registry record.

The single-group, unmasked design has no randomized control group. The dose-stage groups do not provide a like-for-like control comparison. Consequently, the design cannot support a randomized treatment contrast, and the registry does not describe methods to address potential confounding in comparisons between dose stages.

Further limitations include the absence of reported secondary outcome results, the lack of a detailed missing-data approach, and no reported multiplicity adjustment or comprehensive analysis plan. The safety summaries list affected counts and selected serious-event percentages, but the record does not report event-level details or the percentage denominators. These gaps constrain assessment of outcome precision, reproducibility, and the completeness of the benefit and safety picture.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dasatinib in Treating Patients With Recurrent Glioblastoma Multiforme or Gliosarcoma — NCT00423735.
• Registry record last updated 2019-07-24; status last verified 2019-07.
• Results first posted 2015-01-06.
• 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

NCT00423735 is a completed phase II, single-group, unmasked trial sponsored by the National Cancer Institute (NCI), with enrollment recorded as 64. It studied dasatinib in patients with recurrent glioblastoma multiforme or gliosarcoma. The treatment schedule was oral dasatinib twice daily on days 1-28, with 28-day courses continuing in the absence of disease progression and unacceptable toxicity.

The primary endpoint was the number of eligible patients who started protocol treatment and achieved 6-month progression-free survival. The registry describes a two-stage design with a null hypothesis of 11%, an alternative hypothesis of 25%, and a decision threshold of 9 or more patients alive without progression at 6 months after Stage 2 accrual and follow-up. It does not report the observed primary endpoint result or whether the threshold was met.

Selected serious adverse-event summaries are recorded for Stage 1 and Stage 1B dose groups. The registry also lists secondary outcomes, but their results are not reported in the registry record. Missing-data methods, a detailed analysis plan, and a randomized comparator are not reported.