Vinblastine, Celecoxib, and Combination Chemotherapy in Treating Patients With Newly-Diagnosed Metastatic Ewing's Sarcoma Family of Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vinblastine, Celecoxib, and Combination Chemotherapy in Treating Patients With Newly-Diagnosed Metastatic Ewing's Sarcoma Family of Tumors (NCT00061893), a na phase 2 study. The primary outcome is Occurrence of Severe Toxicity.

2. Clinical Question

3. Trial Design

This is a phase II, single-group study sponsored by Children's Oncology Group. The registry lists the study as completed, with a start date of 2004-04 and primary completion in 2008-04. Enrollment is recorded as 38. The study title and summary describe treatment of newly diagnosed metastatic Ewing sarcoma family of tumors, using low-dose vinblastine and celecoxib alongside standard combination chemotherapy.

The intervention description characterizes the regimen as a 14-cycle study building on conventional treatment with cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, ifosfamide, and etoposide, and adding vinblastine and celecoxib. The listed intervention record also includes conventional surgery. The registry record does not report dosing schedules, treatment modifications, or how surgery was incorporated into care.

Masking is listed as none, and allocation is listed as not applicable. The model is single-group, so the registry does not describe random assignment or a concurrent comparison arm. This design can describe outcomes among participants treated under the protocol, but it does not by itself isolate the contribution of vinblastine or celecoxib from the other chemotherapy or other aspects of care.

For the primary severe-toxicity evaluation, the record states that all eligible patients who received protocol therapy were considered. Three patients were considered ineligible; the other 35 started protocol therapy and were included in the evaluation population. The registry record does not report a statistical analysis plan, sample-size justification, interim analyses, or methods for handling treatment discontinuation. Event-free survival is listed as a secondary outcome, but its definition and analysis results 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: By protocol design, all eligible patients who received protocol therapy were considered in the evaluation of severe toxicity. Three (3) patients were considered ineligible. All other patients (35) started protocol therapy and are thus included in the evaluation for this measure.

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 Occurrence of Severe Toxicity, measured over The first two cycles (6 weeks) of protocol chemotherapy.

The primary endpoint is the occurrence of severe toxicity during the first two cycles (6 weeks) of protocol chemotherapy. It is a participant-level count outcome: the registry defines an event as grade 3 or higher infection or grade 3 or higher sensory neuropathy during cycles 1-2. The evaluation population comprises the 35 eligible patients who started protocol therapy; the three patients considered ineligible were not included.

The registry description sets out separate criteria for flagging excessive toxicity: 12 or more patients with grade 3 or higher infection, or five or more patients with grade 3 or higher sensory neuropathy, during cycles 1-2. These are decision thresholds stated in the endpoint description, not reported event counts. The observed numbers of participants meeting either criterion are not reported in the registry record, so the endpoint result cannot be reconstructed from the information posted.

In general, an early toxicity endpoint can help characterize treatment burden within a defined period, and an explicit severity grade distinguishes more serious events from lower-grade events. The endpoint is limited to the specified infection and sensory neuropathy events in the stated window; it is not a complete measure of every possible adverse effect or of toxicity across the full 14-cycle regimen. The registry record does not explain why these particular events and thresholds were selected or how the endpoint was analyzed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted information supports a description of the design, endpoint definition, and selected adverse-event counts. It does not provide enough detail to identify the statistical methods used for the primary outcome or event-free survival. Statistical concepts below are general explanations, not claims about analyses performed in this study.

What does the single-group design imply?

The study is recorded as single-group, with allocation not applicable and no masking. In general, a single-group study can describe outcomes observed among participants treated under a specified regimen. It does not contain a concurrent untreated or alternative-treatment group against which to estimate a treatment contrast. Therefore, an event frequency observed in this setting cannot, by itself, show how outcomes would have differed under another regimen. The registry record does not report a controlled comparison or a statistical adjustment intended to create one.

What is the primary endpoint counting?

The primary outcome is a count of participants with specified events during the first two cycles (6 weeks): grade 3 or higher infection or grade 3 or higher sensory neuropathy. The registry says the severe-toxicity evaluation included the 35 eligible patients who started protocol therapy. A participant-level count is different from a count of all episodes: the record’s endpoint wording focuses on whether patients experienced the defined toxicity, not on the number of repeated episodes. The reported endpoint result and any handling of participants with incomplete observation during this window are not reported in the registry record.

How should the flagging thresholds be read?

The endpoint description says the regimen would be flagged for excessive severe toxicity if 12 or more patients had grade 3 or higher infection, or five or more had grade 3 or higher sensory neuropathy during cycles 1-2. These are stated thresholds, not the observed results. They apply to the particular events and period named in the endpoint definition. A threshold-based rule is not the same as a confidence interval or a hypothesis test: it states a criterion for flagging, but it does not quantify the uncertainty around an observed frequency. The registry record does not report the rationale for these thresholds or whether any additional decision rules were used.

What would a confidence interval add?

In general, a confidence interval presents a range of values compatible with the observed data under a specified statistical procedure. It communicates precision, which is affected by the amount of information and the variation in the data. A point estimate without an interval can leave readers unable to judge how uncertain the estimate is. No confidence interval for the primary endpoint is reported in the registry record, and the event counts needed to reproduce one are not reported there either. No interval should be inferred from the adverse-event summaries because those summaries do not give the primary endpoint’s required counts under its specific definition.

What do the sample-size assumptions describe?

The record’s planning illustration is described as a calculation based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations express participants per arm for a chosen power; time-to-event calculations are described as total event counts. These are planning illustrations, not the design of this single-group study and not observed power. The registry record does not report the trial’s own sample-size justification, and the assumptions in an illustrative two-arm calculation do not turn this study into a two-arm comparison.

In general, power is a design-stage probability tied to assumptions about an effect, variability, significance level, and analysis. It is not a measure of whether a completed study has demonstrated an effect. A retrospective calculation based on an observed result can be particularly difficult to interpret as evidence, because it is determined by that result and its assumptions. No claim about observed power is supported by the registry record.

Why can over-dispersion matter?

In general, over-dispersion means that observed variation is greater than a statistical model expects. It can make standard errors too small if a model assumes less variation than the data contain, producing intervals or tests that appear more precise than warranted. The primary endpoint is described as a participant count for defined events, not as a repeated-event rate model. The registry record does not report a model, dispersion estimate, or any analysis of over-dispersion, so there is no basis to say that this issue was assessed in the trial.

Which analyses are documented?

The registry lists two outcome measures and zero analyses. Event-free survival is the named secondary outcome; its definition, estimates, and methods are not reported in the registry record. The primary outcome’s observed result is also not reported. In general, statistical interpretation depends on knowing the analysis population, endpoint definition, missing-data handling, model or summary measure, and precision estimates. Most of those details are unavailable here, so the posted record permits only a limited design and safety description rather than a full reconstruction of the statistical analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and zero analyses. Occurrence of severe toxicity is identified as the primary outcome, and event-free survival is listed as a secondary outcome. The record does not report event-free survival results, its definition, or any associated analysis. It also does not state whether there were additional exploratory outcomes beyond the listed measures.

Multiplicity arises in general when multiple outcomes, time points, subgroup analyses, or statistical tests are considered. If many tests are conducted, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for that. Whether and how multiplicity was handled in this trial is not reported in the registry record. No adjustment method, hierarchy of tests, or prespecified testing procedure is described.

Missing-data methods are also not reported in the registry record. For the severe-toxicity endpoint, the record identifies 35 eligible patients who started protocol therapy as the evaluation population, but it does not describe completeness of observation through cycles 1-2 or how incomplete records were treated. The registry does not report whether participants who stopped treatment early, missed assessments, or had unavailable toxicity grades were handled in any particular way.

The analysis populations for outcomes other than the specified severe-toxicity evaluation are not described. The record does not identify an intention-to-treat analysis, a per-protocol analysis, or a method for accounting for deviations from protocol. These omissions do not establish that no such procedures were used; they mean the procedures are not reported in the registry record. Without the analysis population, missing-data approach, and outcome results, readers cannot assess whether exclusions or incomplete follow-up may have affected the reported findings.

11. 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: neutrophil count decreased (54.3%), infections and infestations - other, specify (51.4%), platelet count decreased (45.7%), white blood cell decreased (45.7%), febrile neutropenia (42.9%).

The posted safety summary records 35 participants at risk for serious adverse events, of whom 33 were affected. For other adverse events, 35 were at risk and 34 were affected. The registry also lists the leading serious adverse-event terms with percentages: neutrophil count decreased (54.3%), infections and infestations - Other, specify (51.4%), platelet count decreased (45.7%), white blood cell decreased (45.7%), febrile neutropenia (42.9%), and hypokalemia (40.0%). These are the terms and figures recorded in the safety summary.

The participant counts and term percentages answer different descriptive questions. The affected counts indicate how many participants are recorded as having at least one event in the relevant summary category; the term percentages describe the listed event terms. They should not be treated as the primary endpoint count. The primary endpoint is restricted to grade 3 or higher infection or grade 3 or higher sensory neuropathy during the first two cycles (6 weeks), while the safety summary is not presented with that same endpoint definition and time window. The registry record does not report the time window or detailed counting rules for the safety summary.

Deaths are not reported in the registry record. The safety figures alone do not establish causation, comparative risk, or the full pattern of events across the treatment course. The study has no concurrent comparator group in the registry design, so these figures are descriptive of the recorded study group.

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

The registry record establishes that a phase II, single-group study evaluated a multiagent chemotherapy regimen that added low-dose vinblastine and celecoxib for newly diagnosed metastatic Ewing sarcoma family of tumors. It defines a primary severe-toxicity endpoint during the first two cycles (6 weeks), and it specifies thresholds for flagging excessive toxicity. It also records that 35 eligible patients who started protocol therapy were included in that endpoint’s evaluation population.

However, the actual primary endpoint counts are not reported in the registry record. Consequently, the record does not show whether the infection or sensory neuropathy threshold was met. It does not report a primary endpoint estimate with a confidence interval or a statistical test. The posted adverse-event summary supplies participant counts and selected term percentages, but it is not a substitute for the missing primary endpoint result because the endpoint definitions and reporting windows are not shown to be the same.

The study’s single-group design also limits interpretation. It describes outcomes among patients receiving the full regimen, but there is no concurrent comparator in the registry record to separate the contribution of the added agents from the backbone chemotherapy or other care. The registry’s brief summary states the study’s purpose as investigating effectiveness, but the posted information does not report an efficacy result. Event-free survival is named as a secondary outcome, but its result and analysis are not reported in the registry record.

These limitations do not establish that the regimen caused a particular outcome or that a particular outcome did not occur. They define what the registry record supports: a description of the study design, endpoint rules, evaluation population, and selected safety summaries. Treatment effects, comparative safety, and the precision of the primary endpoint estimate cannot be determined from the posted results alone.

13. Why This Trial Matters Statistically

This study illustrates why endpoint definition and reporting completeness matter in clinical-trial interpretation. The primary endpoint is specific: it concerns grade 3 or higher infection or grade 3 or higher sensory neuropathy during the first two cycles (6 weeks). The record also distinguishes the evaluation population from total enrollment: 38 were enrolled, three were considered ineligible, and 35 who started protocol therapy were included in the severe-toxicity evaluation. Those details identify what the endpoint was intended to count and in whom.

At the same time, the endpoint’s threshold rules are not results. A registry may state in advance what would trigger a flag, but readers need observed event counts to learn whether that criterion was reached. Here, those counts are not reported in the registry record. This makes the distinction between a defined statistical decision rule and evidence about the observed outcome especially important.

The single-group design also provides a useful example of the boundary between descriptive and comparative evidence. A study can document outcomes in a treated group, yet without a concurrent comparator it cannot directly estimate how outcomes differ under another regimen. This limitation is particularly relevant when a regimen combines several agents and other treatment components, since the observed experience belongs to the regimen as a whole.

Finally, the safety summary and the primary toxicity endpoint should not be conflated. Their reporting categories and time windows are not stated to be equivalent. The registry lists event terms and participant counts, but does not supply the primary endpoint result or analysis details. Together, these features show why statistical reading requires attention to the outcome definition, analysis population, comparison structure, precision, and completeness of reporting—not only the presence of numerical safety summaries.

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 main trial-specific limitation is the single-group design. Allocation is recorded as not applicable, and the registry does not identify a concurrent comparison arm. The outcomes therefore describe participants treated under the combined regimen, without a direct within-trial comparison to standard chemotherapy alone or another regimen. The effects of vinblastine and celecoxib cannot be separated from the other listed drugs or components of care on the basis of this design.

The registry record does not report the observed primary severe-toxicity counts, a confidence interval, or a statistical test. Although the endpoint and flagging thresholds are described, readers cannot determine from the posted information whether either threshold was reached. Event-free survival is listed as a secondary outcome but its definition and result are not reported in the registry record.

The safety summary reports participant counts and selected event-term percentages, but the time window and detailed event-counting rules are not reported in the registry record. Those summaries should not be assumed to represent the primary endpoint’s first-two-cycle window or its specific grade and event criteria. Deaths are not reported in the registry record.

The registry does not report participant characteristics, eligibility details, treatment adherence, dose modifications, follow-up completeness, missing-data methods, or analysis methods. It also does not report a sample-size justification, interim analyses, or a statistical analysis plan. The severe-toxicity evaluation population is described, but equivalent analysis-population details for other outcomes are not available. These reporting gaps restrict assessment of precision, potential selection effects, and the extent to which the posted results represent the planned analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Vinblastine, Celecoxib, and Combination Chemotherapy in Treating Patients With Newly-Diagnosed Metastatic Ewing's Sarcoma Family of Tumors — NCT00061893.
• Registry record last updated 2019-02-15; status last verified 2019-01.
• Results first posted 2013-03-12.
• 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

NCT00061893 is a completed phase II, single-group study sponsored by Children's Oncology Group. It enrolled 38 participants and evaluated a 14-cycle combination chemotherapy regimen for newly diagnosed metastatic Ewing sarcoma family of tumors, adding low-dose vinblastine and celecoxib to a conventional multiagent backbone. Masking is recorded as none, and allocation is not applicable.

The primary endpoint is occurrence of grade 3 or higher infection or grade 3 or higher sensory neuropathy during the first two cycles (6 weeks). Three patients were considered ineligible; the 35 eligible patients who started protocol therapy were included in the endpoint evaluation. The registry states thresholds for flagging excessive toxicity but does not report the observed primary endpoint counts or analysis.

The safety summary records 33 of 35 participants affected by serious adverse events and 34 of 35 affected by other adverse events, with selected event terms and percentages. Event-free survival is listed as a secondary outcome, but its results are not reported in the registry record. Comparative effects and the precision of the primary endpoint cannot be assessed from the posted information.