Thalidomide and Temozolomide in Relapsed or Progressive CNS Disease or Neuroblastoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Thalidomide and Temozolomide in Relapsed or Progressive CNS Disease or Neuroblastoma (NCT00098865), a na phase 2 study. The primary outcome is Therapy Completion Rate.

2. Clinical Question

3. Trial Design

This completed study is registered as a phase II pilot study of thalidomide with temozolomide in young patients with relapsed or progressive brain tumors or recurrent neuroblastoma. The registry records enrollment as 15. Dana-Farber Cancer Institute is listed as the sponsor. The recorded start is 2002-09 and the primary completion is 2010-06.

The design is single-group, with allocation listed as not applicable and masking listed as none. Participants received the combination; there is no registered concurrent comparator group. This design can describe the experience of participants treated in the study, but it cannot isolate the effect of the combination by comparing outcomes with a control group. The record does not describe a randomization procedure or a blinded assessment process.

The intervention description gives a 28-day cycle. Thalidomide was taken orally on days 1–28, initiated at 3 mg/kg and increased as tolerated to a maximum dose of 24 mg/kg or 1000 mg. Temozolomide was taken orally on days 1–5. Its description mentions dosing at 200 mg/m2 or 150 mg/m2 for patients who had previously received significant treatment, but the text is truncated, so the full dosing qualification is not reported in the registry record.

Overall response and overall survival are listed as secondary outcomes. The primary endpoint was therapy completion at 6 months, defined as completing that duration of the combination. Further details of eligibility, follow-up procedures, treatment adherence assessment, and outcome-assessment methods are not reported in the registry record. The registry marks the trial as completed, but completion status does not itself establish that outcome estimates or a full statistical report are available.

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: For pediatric patients with relapsed or progressive brain tumors and neuroblastoma.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis dataset is comprised of all treated patients.

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: The analysis population represents all enrolled and treated patients.

6. Primary Endpoint

The registry lists the primary outcome as Therapy Completion Rate, measured over 6 months.

The primary endpoint is the therapy completion rate at 6 months. The registry defines feasibility as completion of 6 months of thalidomide with temozolomide therapy, and defines the rate as the proportion of patients who completed that duration. Its analysis population is described as all treated patients. This endpoint therefore concerns whether participants remained on and completed the specified course, rather than directly measuring tumor response or survival.

Completion can be used as a feasibility measure because it describes whether the treatment schedule was completed in the study population. It is distinct from a measure of clinical benefit: completing therapy does not by itself establish a change in tumor status or length of survival. Overall response and overall survival are listed separately as secondary outcomes.

The primary outcome description specifies a 90% confidence interval, but the completion count, estimated rate, and interval limits are not reported in the registry record. Without those results, the precision of the estimated completion rate cannot be assessed. The record also does not report the reasons participants may or may not have completed therapy, so the endpoint definition alone cannot explain the pattern of completion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry is sparse. The primary endpoint is a proportion, and the record identifies a 90% confidence interval as its uncertainty measure. The trial is described as single-group, and its primary analysis population is all treated patients. The numerical estimate and confidence-interval limits are not reported in the registry record. The explanations below describe the general meaning of these methods, not additional analyses of this trial.

What does a completion proportion represent?

A proportion expresses the share of an analysis population meeting a defined condition. In this study, the condition is completing 6 months of thalidomide with temozolomide therapy. The registry’s definition makes the endpoint interpretable as a treatment-completion measure among treated patients. It is not equivalent to a response rate or a survival estimate, which address different outcomes.

Interpreting a proportion requires knowing both the number who met the endpoint and the denominator used to calculate it. The registry names the analysis population as all treated patients, but does not report the number who completed therapy or the numerical completion rate. It also does not provide enough information to assess whether all treated patients had complete endpoint follow-up or how participants with incomplete follow-up were handled.

What does a confidence interval add?

In general, a confidence interval communicates the uncertainty around an estimate under the statistical method used to construct it. A wider interval indicates less precision than a narrower interval, though the interval’s meaning depends on the method and assumptions. The registry specifies a 90% confidence interval for the primary measure, but does not report its limits or the method used to calculate it. Without the estimate and interval, the primary result’s precision cannot be evaluated.

A confidence interval is not a guarantee that the true value lies within the reported limits, and it does not by itself determine whether a result is clinically important. It describes statistical uncertainty under a model and procedure. For this study, no interval values are available to interpret, and no threshold for a completion rate that would qualify as feasible is reported in the registry record.

What can a single-group design establish?

In general, a single-group study can describe outcomes observed among participants who receive an intervention. It lacks a concurrent control group, so it cannot directly separate the effect of treatment from other influences on outcomes. This matters for both clinical outcomes and treatment completion. Differences between the enrolled group and an imagined alternative group cannot be measured from the registered design.

The record lists allocation as not applicable and masking as none. These entries characterize the registered design, but the registry does not give further details about outcome-assessment procedures or the handling of potential bias. In particular, there is no registered randomized comparison to support a causal contrast between treatment groups.

How should the planning assumptions be read?

The registry describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial itself used that design. They do not turn this single-group study into a two-arm comparison, and they are not a measure of observed power.

Planning sample sizes are conditional on assumptions about the effect and analysis. They are not observed participant counts and cannot establish what this pilot could reliably detect. The record does not report a sample-size justification for the study’s original design or identify those planning illustrations as the trial’s prespecified analysis plan. It is important to keep such illustrations separate from trial results.

What remains unclear about the analyses?

Overall response and overall survival are listed as secondary outcomes, but the registry does not report numerical estimates or analysis methods for them. The record does not describe statistical models, covariate adjustment, hypothesis tests, or methods for time-to-event analyses. It also does not report a prespecified statistical analysis plan. These omissions mean that the methodological detail available for independent assessment is limited.

General statistical interpretation depends on both estimates and methods. Here, the registry gives the primary endpoint definition and a confidence-interval designation, but not the result or enough computational detail to reproduce it. Accordingly, interpretation should remain focused on what the record expressly states: the study design, endpoint definition, listed outcomes, and recorded safety figures.

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("Thalidomide and Temozolomide")
n      <- c(15)
events <- c(0)
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  Thalidomide and Temozolomide  15  0  0.0  0.0  21.8  0.0  20.4  0.2  20.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists therapy completion as the primary outcome and overall response and overall survival as secondary outcomes. It does not report how the study handled the possibility of testing or interpreting multiple outcomes, whether a hierarchy was prespecified, or whether any adjustment for multiplicity was used. Without such details, the secondary outcomes should be treated as listed outcome areas, not as confirmatory findings. Their numerical results are not reported in the registry record.

The primary outcome analysis population is described as all treated patients. The record does not report how missing endpoint information was handled, whether participants without a full follow-up assessment were counted as not completing therapy, or whether any imputation or sensitivity analysis was used. These details matter because a proportion can depend on how participants with unknown outcomes are treated. The completion count and rate are also not reported, preventing assessment of the denominator in practice.

The registry does not describe exclusions from the analysis population, protocol deviations, or whether every treated participant contributed to every outcome analysis. The secondary outcome populations and methods for handling missing response or survival information are not reported in the registry record. An analysis population for the safety entries is indicated by the at-risk counts, but further rules for collecting or coding adverse events are not stated.

The absence of these details does not show that missing data or multiplicity affected the results. It means that the record does not allow those possibilities to be evaluated. No unreported analysis choices should be assumed.

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: neutrophils (33.3%), leukocytes (26.7%), platelets (26.7%), hemoglobin (13.3%), lymphopenia (13.3%).

The registry records 15 participants at risk for serious adverse events, with 9 affected, and 15 at risk for other adverse events, with 14 affected. It also lists serious adverse-event terms and percentages: Neutrophils, 33.3%; Leukocytes, 26.7%; Platelets, 26.7%; Hemoglobin, 13.3%; Lymphopenia, 13.3%; and ALT, SGPT, 13.3%. The registry identifies the event measure as the percentage of participants with an event.

These entries describe reports within the study group; they do not provide a control-group comparison or establish whether the combination caused an event. The listed terms are event categories, not measures of severity beyond their placement in the serious adverse-event list. The record does not provide additional clinical detail about timing, duration, management, or attribution.

The adverse-event entry has no reported death value. That missing value should not be read as zero deaths: deaths are not reported in the registry record. The available figures also do not establish the full safety profile, since the registry provides only the listed counts and terms in this record.

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

The registry record establishes that a phase II pilot study evaluated thalidomide with temozolomide in young patients with relapsed or progressive brain tumors or recurrent neuroblastoma. Its primary endpoint was completion of 6 months of therapy, defined as a feasibility measure. The record identifies the analysis population as all treated patients and specifies a 90% confidence interval, but it does not report the completion estimate or its interval.

That distinction is central: an endpoint definition is not an endpoint result. The record does not show what proportion completed treatment, how precise an estimate would be, or why participants may have discontinued. Overall response and overall survival appear as secondary outcomes, but numerical results for those outcomes are not reported. Neither the primary nor secondary outcome information in this record supports a conclusion about benefit.

The design also limits what could be concluded even if descriptive outcomes were available. Because the trial is single-group and has no concurrent comparator, the record cannot provide a direct comparison with another regimen or with no treatment. Outcomes observed among participants would be descriptive of the study group and would not by themselves establish what would have happened under an alternative approach.

The safety entries report affected participants and selected serious adverse-event terms. They are useful as descriptions of events recorded in the study, but are not comparative estimates and do not establish causation. The missing death value cannot be interpreted as no deaths.

Thus, the record supports a concise account of the study’s question, design, endpoint definition, and reported safety entries. It does not provide enough outcome information to judge the completion rate, response, survival, or comparative effects. No conclusion that the treatment works or does not work follows from the information recorded.

14. Why This Trial Matters Statistically

This trial illustrates why the definition of an endpoint and its observed result must be distinguished. Therapy completion at 6 months was selected as the primary measure of feasibility, which addresses whether participants completed the planned duration. That is a different statistical question from whether tumors responded or how long participants survived. The registry lists response and survival separately as secondary outcomes.

The study also illustrates the interpretive limits of a single-group design. A treatment cohort can supply descriptive information, including completion and adverse-event experience, but the design does not offer a concurrent control for estimating a comparative effect. The registry’s allocation entry is not applicable, and the study is explicitly recorded as single-group. Those features should shape how any reported outcomes are understood.

Precision is another important part of statistical reporting. The primary outcome description specifies a 90% confidence interval, but the estimate and interval limits are absent from the registry record. Without them, readers cannot evaluate the uncertainty around the completion rate. A named confidence-interval method is not enough to convey the result when the numerical values are unavailable.

Finally, the record shows how missing details affect evaluation of an analysis. The treated-patient population is identified, but missing-data handling, outcome-analysis methods, and multiplicity procedures are not reported. The available safety counts remain descriptive, and an unreported death value cannot be treated as a zero. Careful interpretation means preserving those distinctions rather than filling gaps with assumptions.

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 principal limitation of the registry information is that it does not report the primary completion result, despite defining the endpoint and specifying a 90% confidence interval. The number completing therapy, the estimated proportion, and interval limits are absent. This prevents assessment of both the outcome level and its precision. The registry also does not report numerical findings for the listed secondary outcomes, overall response and overall survival.

The study’s single-group design creates a separate limitation. There is no concurrent comparator, so the record cannot establish a treatment contrast. Even a complete set of descriptive outcomes would not, on its own, resolve what outcomes might have occurred under another treatment or no treatment.

Details needed to assess endpoint ascertainment and analysis are limited. The record does not report missing-data methods, reasons for non-completion, criteria for outcome assessment, or the methods used to calculate the confidence interval. It does not describe multiplicity handling or a statistical analysis plan. Eligibility details and participant ages are also not reported in the registry record.

The intervention description is incomplete: the temozolomide dosing qualification is truncated. Safety reporting includes affected counts and selected serious-event terms, but does not give further context such as event timing, attribution, or duration. Deaths are not reported in the adverse-event entry. These limitations constrain interpretation; they do not establish that unreported outcomes or events did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Thalidomide and Temozolomide in Relapsed or Progressive CNS Disease or Neuroblastoma — NCT00098865.
• Registry record last updated 2014-10-07; status last verified 2014-09.
• Results first posted 2014-09-25.
• 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

NCT00098865 is a completed phase II pilot study sponsored by Dana-Farber Cancer Institute. It evaluated thalidomide with temozolomide in young patients with relapsed or progressive brain tumors or recurrent neuroblastoma. The registry records enrollment as 15, a single-group design, no masking, a start of 2002-09, and primary completion in 2010-06.

The primary endpoint was the proportion of treated patients completing 6 months of therapy, with a 90% confidence interval specified. The numerical endpoint result is not reported in the registry record. Overall response and overall survival are listed as secondary outcomes, without numerical results in the record. Safety entries report affected participants and selected serious adverse-event terms; deaths are not reported. The record supports description of the study and its reporting, but not a comparative treatment-effect conclusion.