Phase II Imatinib + Hydroxyurea in Treatment of Patients With Recurrent/Progressive Grade II Low-Grade Glioma (LGG): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Imatinib + Hydroxyurea in Treatment of Patients With Recurrent/Progressive Grade II Low-Grade Glioma (LGG) (NCT00615927), a non-randomized phase 2 study. The primary outcome is 12-month Progression Free Survival (PFS).

2. Clinical Question

The secondary objectives concerned progression-free survival, overall survival, objective response, and safety and tolerability. These objectives describe what the investigators planned to assess; they do not establish that numerical findings or analyses are available. The registry lists secondary outcome measures, but the posted record does not give their results.

3. Trial Design

This is a Phase II study of imatinib mesylate plus hydroxyurea in patients described in the title and objectives as having recurrent or progressive grade II low-grade glioma. The registry classifies the allocation as non-randomized, the masking as none, and the model as single-group. It lists Duke University as the sponsor and records the study as completed. The recorded enrollment is 64.

The registry describes grade II astrocytoma and grade II oligodendroglioma or oligoastrocytoma groups. Those labels describe histology, not separate randomized treatment arms. Both groups are associated with the combination intervention, and the registry warns that the arms are not a like-for-like control comparison. Consequently, differences between group results, if reported elsewhere, could not be read as a randomized estimate of one treatment versus another from this design alone.

The study start is recorded as 2006-02, and primary completion as 2009-04. The intended primary outcome was 12-month progression-free survival. Secondary outcomes listed include median progression-free survival, median overall survival, objective response rate, and safety and tolerability. The record lists five outcome measures, but it reports zero analyses. The numerical primary endpoint result, secondary efficacy estimates, and associated confidence intervals are not reported in the registry record.

The record does not report a separate control group, a randomization procedure, or masking. It also does not report the treatment schedule, dose details, protocol deviations, or a statistical analysis plan. These omissions limit what can be concluded about how the trial was conducted and how endpoint estimates would have been derived. The completion status indicates the registry's administrative status for the study, not that any particular efficacy or safety conclusion follows.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as 12-month Progression Free Survival (PFS), measured over 12 months.

The primary endpoint is the percentage of participants who remain alive without disease progression through 12 months from the start of cycle 1. The registry defines progression-free survival as the time from that cycle start to the first documented progression under modified Macdonald criteria, or to death from any cause. Counting death as an event means that a participant does not need to have documented tumor progression for the endpoint to be reached.

A fixed-time progression-free survival percentage offers a direct description of the proportion meeting the endpoint at a clinically specified follow-up point. It can be easier to communicate than a time-to-event curve, while the underlying outcome still depends on follow-up and on the recorded timing of progression or death. The percentage alone does not describe when events occurred or how long participants were followed beyond the stated endpoint time.

The registry identifies the unit as a percentage of participants and the intended dispersion measure as a 95% confidence interval. However, neither the endpoint percentage nor its interval is reported in the registry record. The record also does not state how participants with incomplete follow-up were handled for this result, whether any were censored before the endpoint time, or which analysis population was used. Those details matter when interpreting a fixed-time estimate, because an observed proportion and an estimate that accounts for incomplete follow-up need not represent the same calculation.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group, non-randomized Phase II study without masking. These design labels determine the kinds of statistical conclusions that are supportable. A single-group study can describe outcomes among participants who receive the intervention, but it does not provide a concurrent randomized estimate of what would have happened under a different treatment. Non-random allocation also means that comparisons between the histology groups should not be treated as balanced treatment comparisons. The registry itself cautions that the arms are not a like-for-like control comparison.

What does the primary endpoint estimate?

The primary endpoint is the percentage of participants alive without progression at 12 months. The underlying time-to-event definition begins at the start of cycle 1 and ends at the first documented progression according to modified Macdonald criteria or death from any cause. The endpoint therefore treats either progression or death as an event. A fixed-time percentage is a snapshot of event-free status at the stated follow-up point; it is not the same as a median time to progression-free survival, which describes the time at which the estimated event-free proportion reaches a specified point.

The registry identifies a 95% confidence interval as the intended measure of dispersion. In general, a confidence interval conveys the uncertainty associated with an estimate under the method used to calculate it. A narrower interval indicates greater precision than a wider interval, while neither an interval nor a point estimate alone establishes a causal treatment effect. Here, no endpoint estimate or interval is reported, so precision cannot be judged.

Why does time-to-event follow-up matter?

Time-to-event methods are useful when participants may have different lengths of observation or when follow-up ends before an event is observed. In general, censoring means that an event time is not fully observed for a participant, even though information up to a last known follow-up time may be available. A time-to-event analysis can use that partial follow-up under its assumptions. The registry record does not report the censoring method, follow-up distribution, or handling of incomplete data for the primary endpoint. It is therefore not possible to determine from the record whether the reported endpoint, if any, was calculated as a simple proportion or through a time-to-event estimate.

The definition includes death from any cause as an event. This prevents a participant who dies without a prior documented progression from being counted as progression-free after death. The endpoint consequently combines progression and death into one outcome and does not distinguish their separate contributions. The registry does not report event counts or separate estimates for progression and death.

What does the design allow researchers to compare?

Randomization is a way to allocate participants so that, on average, treatment groups can be compared with less risk of systematic differences at baseline. This study is not randomized and is listed as a single-group model. The two histology descriptions identify participant categories, not a randomized control arm. Thus, even if separate group results were available, a difference between them could reflect differences in disease type or other characteristics rather than an effect of treatment. No comparative treatment estimate is reported.

In a single-group study, the observed endpoint can be described for the participants included in the analysis. A treatment effect, however, is a comparison against an appropriate alternative outcome, which is not available from the design described in the registry. Historical or external comparisons would require information and assumptions not reported in the registry record and should not be inferred.

What can be said about analysis and planning?

The record lists five outcome measures and zero analyses. It gives no statistical analysis plan, no method for calculating the primary endpoint, and no account of interim analyses or sample-size justification. These items are not reported in the registry record. The enrollment entry is a registry fact; it should not be mistaken for proof of a particular power calculation or of the number included in an endpoint analysis.

In general, sample-size planning considers the endpoint, expected effect, variability, significance level, and desired power. A planning illustration based on an observed effect is not observed power and does not describe the trial's original design unless the record establishes that it was used prospectively. No numerical planning result is available in the registry record. It is not possible to reconstruct the investigators' assumptions or their rationale.

Finally, statistical significance and clinical importance are distinct ideas. A confidence interval can help show which effect sizes are compatible with the data under the analysis assumptions, while a prespecified threshold or clinical context is needed to judge importance. Neither the endpoint estimate nor a decision threshold is reported. Statistical interpretation must therefore remain limited to the design and definitions that the registry actually records.

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("Astrocytoma", "Oligodendroglioma")
n      <- c(32, 32)
events <- c(14, 11)
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  Astrocytoma  32  14  43.8  26.4  62.3  28.2  60.7  28.1  60.8
ARM  Oligodendroglioma  32  11  34.4  18.6  53.2  20.4  51.7  20.4  51.8

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes or analyses are examined: the more opportunities there are to identify an apparently notable result, the more important it is to understand which outcomes were prespecified and how the analysis addressed multiple testing. The registry lists a primary endpoint and secondary outcomes covering progression-free survival, overall survival, objective response, and safety and tolerability. It records five outcome measures and zero analyses. The analysis methods and any multiplicity adjustment are not reported in the registry record.

The primary endpoint is identified as 12-month progression-free survival, but the record does not provide its result or a statistical analysis plan. Without the plan, it is not possible to determine whether secondary outcomes were confirmatory or exploratory, whether there were additional analyses, or how the investigators handled repeated testing. No correction or testing hierarchy should be assumed.

Missing-data handling is also not reported in the registry record. The endpoint depends on follow-up through 12 months, and the record does not describe how participants with incomplete follow-up were classified, censored, or included in an analysis. It does not identify the analysis population, describe exclusions, or report the amount or pattern of missing outcome information. These omissions make it impossible to assess whether incomplete follow-up could affect the endpoint estimate or its uncertainty.

The registry does not report interim analyses, protocol deviations, or a prespecified statistical plan. Their absence from the record does not establish that they did or did not occur; their status is not reported in the registry record. As a result, the scope of outcome selection and the robustness of any analysis cannot be evaluated from these entries.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nausea (9.4%), vomiting (6.2%), death nos (6.2%), seizure (6.2%), anemia (3.1%).

The registry separates serious adverse events from other adverse events and reports figures by histology group. For astrocytoma, serious adverse events affected 10 of 32 participants at risk, while other adverse events affected 28 of 32. For oligodendroglioma, serious adverse events affected 3 of 32 participants at risk, while other adverse events affected 28 of 32. These are group-specific entries, not a randomized safety comparison.

The registry's listed serious-event terms include nausea at 9.4%, vomiting at 6.2%, death NOS at 6.2%, seizure at 6.2%, anemia at 3.1%, and cardiac disorders—other, specified as coronary artery disease, at 3.1%. A listed event term and percentage do not show whether an event was considered related to treatment, how severe it was, or when it occurred. Attribution and detailed clinical context are not reported in the registry record.

The group fields for deaths are null, while death NOS appears among the serious-event terms. These entries should not be merged into a conclusion about treatment-related mortality: the record does not explain the relationship between the term list and the group death fields. Serious adverse-event counts also do not describe all tolerability outcomes, and the registry does not report a complete safety narrative or exposure-adjusted analysis.

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

The record supports a description of the research question and study structure. It describes a Phase II investigation of imatinib mesylate plus hydroxyurea for progressive or recurrent grade II low-grade glioma, with 12-month progression-free survival selected as the primary endpoint. It also identifies secondary objectives involving survival, response, and safety. These details explain what the study set out to evaluate.

The record does not report the primary endpoint percentage or its 95% confidence interval. It also does not report numerical results for the listed secondary efficacy outcomes. Without those estimates, neither the direction nor size of the observed efficacy findings can be described, and their statistical precision cannot be assessed. The absence of posted results is not evidence that the intervention had a particular effect or that it had no effect.

The design places an additional limit on interpretation. Because the study is non-randomized and single-group, outcomes among treated participants would not by themselves establish what would have occurred under another treatment or no treatment. The histology groups do not provide the randomized control comparison needed to attribute differences to treatment. The registry explicitly cautions against treating them as like-for-like control arms.

The safety entries provide some event counts and serious-event terms, but they do not establish causality. They do not give a full account of timing, severity, treatment exposure, or attribution. The death-related entries are not reconciled in the record. Safety conclusions should therefore be limited to the listed categories and counts, rather than extended to an overall judgment about the combination.

More complete interpretation would require outcome estimates, uncertainty intervals, analysis methods, follow-up details, and an explanation of missing data and analysis populations. Those elements are not reported in the registry record. The record's completion status and enrollment entry do not fill these evidentiary gaps. The statistics available establish what was intended and some reported safety categories, not a comparative treatment effect or a clinical recommendation.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a registered research question and a reported result. The record identifies a fixed-time progression-free survival endpoint and gives a definition that includes both documented progression and death from any cause. That definition is essential for understanding what the endpoint is intended to capture. Yet the numerical result and its confidence interval are not reported, leaving the central estimate and its precision unavailable.

Its design also makes clear why a treatment outcome is not automatically a treatment effect. A single-group, non-randomized study can describe outcomes in the participants studied, but it does not establish the outcome under a concurrent alternative. The histology categories are not a substitute for randomized controls. The registry's explicit warning about comparability is important when considering any group-level safety figures or potential comparisons.

The record also shows why outcome listings should not be confused with analyses. Several efficacy and safety outcomes are named, but zero analyses are reported. No statistical plan, missing-data approach, analysis population, or multiplicity strategy is reported. These details help determine what estimates mean, how uncertainty should be interpreted, and how much confidence to place in selected findings.

For clinical researchers, the main statistical lesson is that endpoint definition, study design, and result reporting must be read together. A clearly defined endpoint does not reveal its numerical value, and a completed study does not by itself establish a result. The registry record supplies some design and safety details but leaves major elements needed for efficacy interpretation unreported.

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.

Several limitations specific to this record restrict interpretation. The stated target population is recurrent or progressive grade II low-grade glioma, and the arm descriptions identify grade II astrocytoma and grade II oligodendroglioma or oligoastrocytoma. However, the condition list names glioblastoma and gliosarcoma. The registry record does not explain how these labels relate to the intended population or whether they represent coding choices, eligibility categories, or another distinction. The discrepancy should not be resolved by assumption.

The primary endpoint result, its confidence interval, and numerical secondary efficacy findings are not reported in the registry record. The entry lists five outcome measures and zero analyses. Statistical methods for the endpoint, analysis populations, missing-data handling, censoring, follow-up, and multiplicity are not reported. Consequently, the record cannot support assessment of estimate precision, robustness, or consistency across outcomes.

The single-group, non-randomized design does not provide a randomized control comparison. The two histology groups cannot be treated as equivalent treatment arms, as the registry itself cautions. The record also does not describe treatment dose or schedule, protocol deviations, interim analyses, or sample-size justification. These details are not reported in the registry record.

Safety information is partial. Serious and other adverse-event counts are listed by histology group, with a separate list of serious-event terms and percentages. The record does not report event attribution, timing, severity detail, exposure-adjusted rates, or a complete reconciliation of death-related entries. These limits mean that the listed figures describe only the recorded categories and cannot establish an overall causal safety profile.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Imatinib + Hydroxyurea in Treatment of Patients With Recurrent/Progressive Grade II Low-Grade Glioma (LGG) — NCT00615927.
• Registry record last updated 2013-03-15; status last verified 2012-12.
• Results first posted 2013-03-15.
• 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.

19. Record Summary

The registry record describes a completed, non-randomized, unmasked, single-group Phase II study sponsored by Duke University. It records enrollment of 64 and an intervention combining imatinib mesylate with hydroxyurea. The intended population is described as progressive or recurrent grade II low-grade glioma, with astrocytoma and oligodendroglioma or oligoastrocytoma groups.

The primary outcome is the percentage of participants alive without progression at 12 months, with progression-free survival defined from the start of cycle 1 to documented progression or death from any cause. Secondary outcomes include progression-free survival, overall survival, objective response, and safety and tolerability. The record lists five outcome measures and zero analyses.

The primary endpoint result, confidence interval, secondary efficacy findings, statistical analysis plan, and missing-data methods are not reported in the registry record. Some serious and other adverse-event counts and serious-event terms are listed, but the record does not establish causality or provide a complete safety interpretation.