Phase 1 Trial of Oral Ixabepilone: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1 Trial of Oral Ixabepilone (NCT00632424), a non-randomized phase 1 study. The primary outcome is Number of Participants With a Dose-Limiting Toxicity (DLT).

2. Clinical Question

The study asked whether a schedule of oral ixabepilone given as three doses, each separated by six hours, every 21 days could be evaluated for dose-limiting toxicity and safety in participants with advanced cancer. As a Phase 1 dose-finding study, its stated purpose was to determine the maximum tolerated dose for this schedule and describe safety. The primary question was how many participants experienced a dose-limiting toxicity during Cycle 1, defined as Day 0 through Day 21.

The registry record lists enrollment of 23 participants, but does not report the primary endpoint result. It therefore does not show how many participants met the dose-limiting toxicity definition, nor does it report a maximum tolerated dose. The central question can be described from the study purpose and endpoint, but the posted record does not provide the result needed to answer it.

3. Trial Design

This was a Phase 1, non-randomized, single-group study of oral ixabepilone in participants with advanced cancer. The registry record lists enrollment of 23 and identifies advanced solid tumors as the condition. It describes a dose-finding study intended to assess safety and determine the maximum tolerated dose for a schedule of three oral doses separated by six hours, repeated every 21 days. The official title specifies the three-dose schedule, and the brief summary places the doses on Day 1.

The record lists the study start as 2008-05 and primary completion as 2009-06. Its status is terminated. The reason for termination is not reported in the registry record. No further detail about the duration of participation or treatment beyond the dosing schedule is reported in the registry record.

Although the design is identified as single-group, adverse-event results are organized into three dose groupings: Ixa 90 mg/Day, Ixa 120 mg/Day, and Ixa 150 mg/Day. The record does not describe random assignment to these dose groups. The group figures are therefore descriptive; they do not establish a controlled comparison of dose levels. Differences between groups, if any, could not be attributed to dose alone from this record.

Masking is listed as none. No comparator intervention is listed. The available information does not describe how participants entered or moved between dose levels, or how the dose-finding decisions were made. Those protocol details are not reported in the registry record and should not be inferred from the group labels.

The design fits the stated early-phase purpose: the primary endpoint focuses on a count of participants with a defined toxicity during Cycle 1, while secondary outcomes include adverse events, laboratory abnormalities, QTc, pharmacokinetic concentrations, and best overall response. However, the registry record contains no posted analyses for these outcomes. It gives the study question and some safety figures, but not enough information to reconstruct the full dose-finding process or assess its primary endpoint.

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: 23 participants enrolled in this study; five participants were never treated due to not meeting study criteria (n=4) and withdrawal of consent (n=1).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of ixabepilone.

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 Number of Participants With a Dose-Limiting Toxicity (DLT), measured over During Cycle 1 (Day 0 through Day 21).

The primary endpoint is the number of participants with a dose-limiting toxicity (DLT) during Cycle 1, defined as Day 0 through Day 21. The endpoint applies to all participants who received at least one dose of ixabepilone. A DLT had to be considered related to ixabepilone and meet one of the specified toxicity criteria.

The criteria cover severe blood-count abnormalities, including an absolute neutrophil count below 500 cells/mm³ for at least five consecutive days or febrile neutropenia of any duration. They also include Grade 4 thrombocytopenia below 25,000 cells/mm³, or Grade 3 thrombocytopenia with bleeding requiring platelet transfusion. Other criteria include Grade 3 or 4 nausea, vomiting, or diarrhea despite adequate intervention; fatigue; another clinically significant drug-related Grade 3 or higher non-hematologic toxicity; and delayed recovery from toxicity that delays Cycle 2 by at least three weeks. Recovery is specified as to Grade 1 or lower, or baseline, except for alopecia.

In general, a DLT endpoint is useful in dose-finding because it applies a defined set of clinically significant toxicities to a specified observation period. It can support decisions about tolerability when the protocol's decision process and results are available. Here, the registry record states the definition and period, but does not report the number of participants who had a DLT. It also does not report the dose-finding decision or a maximum tolerated dose. The endpoint definition alone cannot establish the observed tolerability of the schedule.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a single-group, non-randomized Phase 1 study. It identifies the primary outcome as a count: the number of participants with a DLT during Cycle 1. The primary outcome is not reported as an analyzed result. There are no analyses listed in the record. The following concepts explain how the design and endpoint can be read; they do not add unreported methods or results.

What does a participant count tell us?

A count records how many participants met an outcome definition. For this endpoint, the definition combines a relationship to ixabepilone, a fixed observation period, and specified toxicity criteria. The count is meaningful only alongside the number of participants who were eligible for that endpoint and actually observed during that period. The record defines the endpoint population as participants who received at least one dose, but does not report the treated population count or the DLT count. Enrollment of 23 is not necessarily the same as the number in the endpoint population.

In general, a count and a proportion answer different questions. A count says how many participants had an event; a proportion relates that count to a defined denominator. A rate may additionally account for time at risk. The registry record's primary outcome is a participant count, and it does not post a primary estimate or interval. The adverse-event table provides group counts at risk and affected, but these are not a substitute for the DLT outcome.

Why does the design matter?

Randomization helps make treatment groups comparable in expectation by assigning participants through a chance process. This study is recorded as non-randomized and single-group, with no comparator listed. Its dose-group safety summaries should therefore be read as descriptions of participants within each group, not as results of a randomized comparison. Even if the group counts differ, the record does not show that the groups were comparable in participant characteristics, treatment exposure, or follow-up.

The dose labels in the adverse-event results are Ixa 90 mg/Day, Ixa 120 mg/Day, and Ixa 150 mg/Day. The registry record does not explain the allocation or movement of participants among these groups. It would be inappropriate to infer a dose-escalation rule, a stopping boundary, or a dose-response analysis from the labels alone.

What does the observation window add?

The DLT endpoint is restricted to Cycle 1, Day 0 through Day 21. A fixed period makes the endpoint definition more reproducible: toxicities outside that window do not automatically qualify under this primary endpoint, even though they may be relevant to other safety outcomes. The specific criteria also make clear that not every adverse event is a DLT. The event must meet a listed clinical threshold and be considered related to ixabepilone.

In general, a defined window can simplify interpretation, but it does not describe all later safety experience. The registry record lists other adverse-event outcomes, but their detailed results and observation periods are not reported beyond the descriptions shown. It does not report whether all participants completed Cycle 1 or how events after the primary window were handled in the endpoint analysis.

How should precision be understood?

A confidence interval is a range of values compatible with the data under a stated statistical method. In general, it communicates uncertainty around an estimate; it does not guarantee that the true value lies within the interval. A small count can be consistent with a fairly broad range of underlying event frequencies, particularly when the denominator is small. No confidence interval for the DLT endpoint is reported in the registry record, so the precision of that outcome cannot be assessed from the posted primary results.

Statistical significance is not the main interpretive tool for a dose-finding count in a single-group study. In general, a p-value summarizes how unusual data would be under a specified null model. It does not measure clinical importance, prove causation, or correct for weaknesses in a design. No primary endpoint test or p-value is reported. The absence of a reported test should not be replaced by an assumed test or a calculation from incomplete information.

How do the sample-size illustrations relate to this study?

The sample-size section presents planning illustrations, not the trial's original design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set as a stated fraction of the observed effect. For time-to-event tables, the convention is to report a total number of events; for other tables, it is participants per arm. These are calculation conventions, not descriptions of this study's non-randomized, single-group design.

In general, planning illustrations describe sample sizes under chosen assumptions. They are not observed power, and they do not show that the trial had a particular probability of detecting an effect after the study was completed. They also cannot recover missing primary results. The registry record does not report a sample-size justification for this trial, and no planning assumption should be mistaken for a protocol decision.

Over-dispersion is a general concern when variability exceeds what a chosen statistical model expects. It can make standard errors too small if the model does not allow for that extra variability. This is often relevant for count outcomes modeled as event rates, but the registry record does not state that a count model or such an adjustment was used. No statistical model for the DLT endpoint is reported in the registry record. It would therefore be speculative to assign a model, adjustment, or variance assumption to the study.

The central methods limitation is simple: the record defines the primary endpoint but does not post its analyzed result or the statistical plan used to analyze it. General statistical concepts can clarify what the endpoint and design imply, but they cannot fill in those missing methods or outcomes.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 9 outcome measures and several secondary outcome domains, including adverse events, laboratory abnormalities, QTc, pharmacokinetic concentrations, and best overall response. Testing or estimating many outcomes can raise a multiplicity concern: in general, the more questions examined, the greater the chance that some findings may appear notable by chance when formal tests are used. Researchers may address this through a prespecified hierarchy, adjusted testing, or an explicitly exploratory interpretation. The statistical plan and any multiplicity adjustment are not reported in the registry record.

No analyses are listed, and the record does not report primary or secondary outcome results for the DLT endpoint or most of the named domains. It is therefore not possible to determine whether the study used hypothesis tests, confidence intervals, descriptive summaries, or a planned sequence of analyses. The registry record does not report interim analyses or stopping rules.

Missing-data handling is also not reported in the registry record. The primary endpoint population is described as all participants who received at least one dose, but the number treated, the number with evaluable Cycle 1 observations, and the handling of incomplete observation are not reported. The enrollment figure of 23 should not be taken as an endpoint denominator without that information.

The record does not describe analysis populations for secondary outcomes, exclusions, or how participants who discontinued treatment were handled. These details matter because different outcome sets can have different denominators and may answer different questions. The serious and other adverse-event group figures include at-risk counts by dose grouping, but they do not establish the analysis population used for the primary DLT endpoint.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chest pain (33.3%), malignant neoplasm progression (33.3%), neutropenic sepsis (16.7%), anaemia (16.7%), thrombocytopenia (16.7%).

The posted serious adverse-event figures are participant counts by dose grouping. In the Ixa 90 mg/Day group, 3 participants were at risk and 2 were affected; in the Ixa 120 mg/Day group, 9 were at risk and 2 were affected; in the Ixa 150 mg/Day group, 6 were at risk and 1 was affected. For other adverse events, the corresponding counts are 3 at risk and 3 affected, 9 at risk and 8 affected, and 6 at risk and 6 affected.

These figures describe the groups shown in the registry record. They are not randomized comparisons, and the record does not establish that the groups were comparable. The counts do not by themselves indicate the severity, duration, recurrence, or causal relationship of every event. Serious adverse events are not the same measure as dose-limiting toxicities: the DLT endpoint has its own Cycle 1 window, relationship requirement, and criteria. The record does not report the primary DLT count.

The listed serious adverse-event terms are chest pain and malignant neoplasm progression at 33.3% each, and neutropenic sepsis, anaemia, thrombocytopenia, and muscular weakness at 16.7% each. The registry record does not clarify whether the same participant could appear under more than one term. These percentages should not be summed or read as mutually exclusive categories. They are descriptive entries, not evidence of a causal comparison between dose groups.

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

The record establishes that this was a Phase 1 dose-finding study of oral ixabepilone in advanced cancer, with a three-dose schedule separated by six hours and repeated every 21 days. It also establishes the stated primary endpoint: the number of treated participants with a defined, ixabepilone-related DLT during Cycle 1. Those details explain what the study set out to examine.

The record does not report the primary endpoint count, an estimate of the maximum tolerated dose, or a statistical analysis of that endpoint. It therefore does not show, on the posted information, whether any particular dose met a dose-limiting toxicity threshold or how the dose-finding objective was resolved. The stated purpose of a study is not a result.

The adverse-event summaries show that affected participants were recorded in each of the three listed dose groupings. They provide a descriptive safety snapshot, along with several serious adverse-event term percentages. They do not show a randomized dose comparison, establish that dose caused a difference, or provide a complete account of adverse events. The record does not report whether events overlapped across terms or how long participants were observed for the adverse-event summaries.

In general, early-phase safety data are interpreted in the context of the protocol, exposure, observation time, and prespecified decision rules. Those details are not all. The posted group counts should not be treated as proof of safety or harm, and this page does not make a treatment recommendation. Nor do the listed outcomes establish a treatment effect: the registry record does not report the best overall response result or a comparator group.

The appropriate conclusion is limited. The registry record describes the dosing schedule and endpoint definitions and posts some adverse-event counts, but does not provide the primary result required to answer the central dose-finding question. The missing outcome and analysis details prevent a complete statistical assessment of the trial.

13. Why This Trial Matters Statistically

This trial is statistically instructive because its central endpoint is clearly defined while its primary result is not posted in the registry record. A detailed endpoint definition can make an outcome reproducible: here, the DLT criteria specify a relationship to ixabepilone, a Cycle 1 window, and a range of hematologic and non-hematologic toxicities. But a definition alone cannot answer the study question. Without the event count and the number of participants evaluated, readers cannot estimate the observed frequency or its precision.

The record also illustrates why design labels matter. It is a non-randomized, single-group study, yet its safety data are presented across three dose groupings. Grouped results can be useful for description, but they do not become controlled comparisons merely because multiple dose levels appear in the record. Randomization and a documented comparison plan would be needed for stronger comparative interpretation; neither is reported.

Another statistical lesson is that different safety outcomes are not interchangeable. The serious adverse-event counts, other adverse-event counts, and primary DLT endpoint have distinct definitions. A participant may contribute to an adverse-event summary without meeting the Cycle 1 DLT criteria. Reading each outcome according to its stated definition avoids treating a broad safety count as a substitute for the dose-finding endpoint.

Finally, this record shows the boundary between what a registry can communicate and what remains uncertain. The record contains study purpose, design, endpoint definitions, and some safety figures, but does not report analyses, a statistical plan, or the primary result. Transparent interpretation should preserve that distinction rather than infer unposted decisions or outcomes.

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 important limitation for interpreting this specific trial is that the primary DLT result is not reported in the registry record. The record gives the endpoint definition and observation window, but not the number of participants with a DLT, the number evaluated for the endpoint, or the maximum tolerated dose. This prevents direct assessment of the study's main dose-finding question.

The registry record lists enrollment of 23, but does not state how many participants received at least one dose or completed the Cycle 1 assessment. The primary endpoint population is defined by treatment receipt, so enrollment alone does not supply its denominator. Missing-data handling and the treatment of participants with incomplete Cycle 1 follow-up are not reported.

The study is non-randomized and single-group, and no comparator is listed. The safety results are grouped by dose, but the record does not describe assignment to those dose groups or establish comparability among them. The group counts cannot support a causal dose comparison. The reason the study was terminated is not reported in the registry record.

The record does not report the statistical analysis plan, a sample-size justification, interim analyses, decision rules for dose finding, confidence intervals, or hypothesis tests. It also does not provide detailed results for the listed secondary outcomes, including laboratory abnormalities, QTc, pharmacokinetic concentrations, and best overall response. The serious adverse-event terms are reported with percentages, but the record does not clarify whether participants could contribute to multiple terms.

These gaps limit conclusions to the information actually posted: design and endpoint descriptions plus the available adverse-event summaries. They do not establish why results are absent, why the trial was terminated, or what the complete participant experience was.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase 1 Trial of Oral Ixabepilone — NCT00632424.
• Registry record last updated 2016-03-10; status last verified 2016-02.
• Results first posted 2010-12-02.
• 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

The registry record describes a Phase 1, non-randomized, single-group study of oral ixabepilone in participants with advanced cancer. The listed schedule is three doses separated by six hours, repeated every 21 days. Enrollment is 23; the study is marked terminated, with a start of 2008-05 and primary completion of 2009-06.

The primary endpoint is the number of participants with an ixabepilone-related dose-limiting toxicity during Cycle 1, Day 0 through Day 21. Its result is not reported in the registry record. The record also posts serious and other adverse-event counts by three dose groupings, but these are descriptive and not randomized comparisons. No analyses are listed. The reason for termination, the statistical analysis plan, and the primary endpoint result are not reported in the registry record.