Ixabepilone in Combination With Carboplatin in Patients With Non-small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ixabepilone in Combination With Carboplatin in Patients With Non-small Cell Lung Cancer (NCT00683904), a non-randomized phase 1 study. The primary outcome is Number of Participants With Dose-limiting Toxicity (DLT).

2. Clinical Question

3. Trial Design

This was a phase I, non-randomized, parallel study of ixabepilone with carboplatin in patients with non-small cell lung cancer as first-line treatment. The registry lists two regimens: ixabepilone 32 mg/m^2 with carboplatin 5 mg/min/mL, and ixabepilone 32 mg/m^2 with carboplatin 6 mg/min/mL. The study is recorded as completed, with enrollment of 12. The registry record gives a start date of 2008-06 and a primary completion date of 2009-09.

Allocation was non-randomized and masking was none. These features matter for interpretation: the arms were not formed by random assignment, and treatment was not masked. The registry record does not describe how participants were allocated, whether one regimen followed the other in a dose-escalation process, or what criteria governed assignment. It therefore does not establish that the arms were intended as a like-for-like comparative test.

The stated purpose was to identify dose-limiting toxicity and determine the maximum tolerated dose and recommended Phase II dose for the combination. The primary endpoint was a participant count for dose-limiting toxicity during days 1 through 21 of Cycle 1. The registry lists secondary outcomes covering adverse events, laboratory abnormalities, blood pressure and heart rate, weight and ECOG performance status, and RECIST response assessments. The number of participants contributing to each secondary outcome, beyond the safety denominators recorded for adverse events, is not reported in the registry record.

Details such as eligibility criteria, treatment administration schedules beyond the stated regimens, follow-up after the primary endpoint window, and procedures for assigning a dose are not reported in the registry record. Those omissions limit the extent to which the study’s conduct can be reconstructed from the 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.

Before assignment: After all participants in Dose Level 1 (ixabepilone, 32 mg/m\^2 + carboplatin, 5 mg/min/mL) have been observed for 1 full 21-day cycle, Dose Level 2 (ixabepilone, 32 mg/m\^2 + carboplatin, 6 mg/min/mL) opened.

Dose Level 1

Reasons for not completing this period:

Dose Level 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants who received at least 1 dose of either ixabepilone or carboplatin

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 Dose-limiting Toxicity (DLT), measured over Days 1 through 21 (Cycle 1).

The primary endpoint counts participants with dose-limiting toxicity during days 1 through 21 of Cycle 1. Its population is defined as all participants who received at least 1 dose of either ixabepilone or carboplatin. The endpoint is a count, rather than a continuous measurement or a time-to-event measure.

The registry definition includes specified severe blood-count toxicities: Grade 4 neutropenia lasting at least 5 days or febrile neutropenia, and Grade 4 thrombocytopenia or bleeding requiring platelet transfusion. It also includes Grade 3 or 4 nausea, vomiting, or diarrhea despite medical intervention, and other drug-related Grade 3 or 4 nonhematologic toxicity. Exceptions are listed for Grade 3 injection-site reaction, fatigue/asthenia, transient arthralgia/myalgia, and transient electrolyte abnormality. The scale labels Grade 1 as mild, Grade 2 as moderate, Grade 3 as severe, and Grade 4 as life-threatening.

In general, a dose-limiting toxicity endpoint is used in early-phase research to identify treatment-related toxicity within a defined observation period and inform decisions about doses for further study. The record’s stated purpose connects this endpoint to determining the maximum tolerated dose and recommended Phase II dose. The observed primary endpoint count and the registry’s determination of a maximum tolerated or recommended Phase II dose are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is described as phase I, non-randomized, unmasked, and parallel. In general, phase I studies emphasize treatment exposure and safety questions, including whether toxicities limit a dose, rather than establishing a comparative treatment effect. The stated purpose was to assess dose-limiting toxicity and determine a maximum tolerated dose and recommended Phase II dose for the ixabepilone-carboplatin combination. The registry record does not report a detailed statistical plan for making those dose decisions.

What does the primary endpoint count?

The primary outcome is a participant count for dose-limiting toxicity in a fixed window: days 1 through 21 of Cycle 1. Each participant is classified according to whether a qualifying toxicity occurred in that window. The definition uses clinical severity grades and specific event criteria, including certain blood-count abnormalities, gastrointestinal toxicities despite medical intervention, and other drug-related severe nonhematologic toxicity, with stated exceptions. This operational definition is important because a count is meaningful only in relation to the event criteria and period during which events are assessed.

In general, counting participants with at least one qualifying event differs from counting the total number of events: one participant can have multiple events while still contributing once to a participant-level count. The posted primary endpoint title is a participant count, but the primary result itself is not reported in the registry record. The record also does not clarify how repeat or overlapping toxicities were handled for this endpoint.

Why does non-random allocation matter?

Random allocation is generally used to make treatment groups comparable, on average, with respect to both measured and unmeasured baseline factors. Because this study was non-randomized, that protection is absent. The record also states that masking was none. These features do not make descriptive counts invalid, but they constrain comparisons: the observed counts cannot by themselves distinguish regimen effects from differences in who entered each group, treatment exposure, or other aspects of care.

The parallel model indicates that the regimens are represented as separate arms. It does not, by itself, explain how participants entered an arm or whether enrollment to one regimen depended on experience with the other. The allocation process and any dose-escalation rules are not reported in the registry record. A reader should not infer a particular escalation design from the presence of two carboplatin doses.

How should sparse event counts be understood?

In general, a proportion or rate estimated from a small group can vary substantially with the event status of a single participant. Confidence intervals convey uncertainty around an estimate; they are not guarantees about the range of future observations. A test of a difference asks whether the observed data are inconsistent with a specified null model, but a non-significant result would not establish equivalence. The registry record does not report confidence intervals, hypothesis tests, or an adjusted comparison for these outcomes.

Over-dispersion is a general concern when a statistical model assumes that events vary less than they do in practice. It can make standard errors too small and intervals too narrow if ignored. However, the primary outcome is described as a participant count, and the registry record does not report a model or a dispersion assessment. It is therefore not possible to say whether an over-dispersion adjustment was relevant or used.

What do the planning calculations represent?

Any displayed sample-size values are planning illustrations derived from the observed effect under stated assumptions; they are not observed trial outcomes and are not a measure of the study’s achieved power. The assumptions described for the illustrations include a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect defined as a stated fraction of the observed effect. These assumptions are not documented as the study’s original design assumptions in the registry record. A planning calculation cannot remedy the uncertainty from non-random allocation or missing primary results.

In general, a planning sample size is conditional on the assumed effect, variability, error rate, allocation, and analysis method. If the assumed effect is based on an unstable estimate from a small study, the resulting illustration can also be unstable. Such calculations are useful for exploring hypothetical future designs, but should not be read as evidence that the current study was adequately powered for a comparison.

What analysis information is absent?

The registry record contains no analysis results for the primary endpoint and does not report a statistical analysis plan. Procedures for missing outcome data, analysis populations beyond the primary endpoint definition, adjustment for covariates, handling of multiple outcomes, and interim analyses are not reported in the registry record. No particular method should be assumed in their absence.

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("Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL", "Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL")
n      <- c(6, 6)
events <- c(0, 1)
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  Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and multiple secondary outcome topics, including adverse events, laboratory values, vital signs, weight, ECOG performance status, and RECIST assessments. Evaluating many outcomes can raise a multiplicity issue: in general, the more statistical tests performed, the greater the chance of at least one apparently unusual result by chance. Whether and how that concern was addressed is not reported in the registry record. The record also does not report which secondary outcomes were treated as confirmatory, whether any adjustment was planned, or whether results were intended to be exploratory.

Missing-data methods and analysis populations are also not described beyond the primary endpoint population, defined as participants who received at least 1 dose of either study drug. The registry record does not report how participants with incomplete follow-up, unavailable laboratory measurements, or unevaluable response assessments were handled. It does not state whether participants were included in each outcome analysis according to treatment received, assigned regimen, or another rule.

The study enrollment is recorded as 12, while the adverse-event summaries list 6 participants at risk in each regimen group. The record does not explain the relationship between enrollment and the outcome-specific denominators, or whether any participants lacked particular assessments. No analysis counts for the primary endpoint are reported. These gaps prevent a reader from reconstructing outcome-specific analysis populations or assessing the potential impact of missing observations.

In general, missingness can affect estimates when the probability of an unavailable measurement is related to participant condition or outcome. Without reasons for missingness and a stated handling method, the direction and size of any resulting bias cannot be determined from the registry record.

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: superior vena caval occlusion (16.7%).

The posted serious-event figures list 6 participants at risk in each group. The number affected is 1 for ixabepilone 32 mg/m^2 with carboplatin 5 mg/min/mL and 0 for ixabepilone 32 mg/m^2 with carboplatin 6 mg/min/mL. The other-event category lists 6 affected participants in each group. These counts are descriptive and should be read alongside their recorded denominators, rather than as a controlled comparison of regimens.

The registry lists superior vena caval occlusion as a serious-event term at 16.7%. It does not report the event’s timing, course, participant-level details, or a treatment attribution in this summary. The number of deaths is not reported in the registry record; a missing death count should not be interpreted as confirmation that no deaths occurred.

In general, serious adverse events and other adverse events are distinct reporting categories, and the terms alone do not establish causation. The summary does not provide the detail needed to determine whether participants had multiple events, how long events lasted, or how event severity was distributed. The counts therefore describe the registry’s posted safety summary, not a complete account of safety or a causal estimate of the effect of either regimen.

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

The record identifies a phase I study designed to examine dose-limiting toxicity with ixabepilone and carboplatin in first-line non-small cell lung cancer. It specifies two combination regimens, a defined primary endpoint window, and the types of toxicity that qualify for the endpoint. It also records limited adverse-event counts. These registry entries explain the study’s safety and dose-finding focus.

The record does not report how many participants experienced the primary endpoint. It therefore does not establish the observed dose-limiting toxicity frequency, a maximum tolerated dose, or a recommended Phase II dose. Although those dose decisions were stated aims, the registry information available for this analysis does not report their results. Nor does it report an efficacy estimate that would support a conclusion about tumor response or clinical benefit.

The adverse-event counts do not establish that either regimen is safer. The study was non-randomized and unmasked, and the registry does not report the allocation process or enough event-level detail to assess exposure, timing, severity, and attribution. A difference in a small descriptive count is not by itself evidence of a treatment effect; matching counts are not proof of equivalence.

In general, statistical uncertainty is especially important when outcomes are uncommon and groups are small. A point estimate can look precise in isolation while still having substantial uncertainty. No interval estimates or inferential tests for the primary outcome are reported in the registry record. Any planning calculations based on an observed effect are hypothetical design illustrations, not evidence that the trial had a particular observed power or could reliably distinguish the regimens.

The appropriate interpretation is therefore narrow: the registry documents the intended dose-finding question and some reported safety counts, but leaves the central primary endpoint result and key analysis details unreported. It cannot support a definitive comparative, efficacy, or dose-selection conclusion on its own.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its stated purpose and design call for a different reading from a conventional randomized efficacy comparison. The central question is dose-limiting toxicity in a defined early treatment window, with the broader aim of informing a maximum tolerated dose and recommended Phase II dose. The endpoint’s operational definition and time window are therefore central to understanding what the study intended to measure.

The non-randomized allocation is equally important. Descriptive arm counts can document what was recorded for participants receiving each regimen, but without randomization they do not isolate the effect of changing the carboplatin dose. This distinction helps prevent an observational contrast from being mistaken for a causal comparison. The absence of masking and missing allocation details further limit what can be inferred about how the groups came to differ.

The record also illustrates why a stated endpoint is not the same as a reported result. The dose-limiting toxicity definition is detailed, but its event count is not reported in the registry record. Without that result, the principal safety question cannot be answered quantitatively from the posted registry information. A trial’s aims, design features, and endpoint definitions should be distinguished from its observed findings.

Finally, the safety summary underscores the limits of sparse counts. The serious-event figures and other-event counts are useful descriptive information, but they do not establish regimen equivalence, causation, or a reliable difference. Statistical interpretation depends not only on arithmetic but also on allocation, denominators, event definitions, uncertainty, and completeness of reporting.

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 is that the primary endpoint result is not reported in the registry record. The count of participants with dose-limiting toxicity, and any conclusion about maximum tolerated or recommended Phase II dose, are unavailable. This prevents direct assessment of the trial’s main stated objective.

The study was non-randomized and unmasked. The registry does not explain how participants were allocated to the two regimens, whether allocation followed a dose-escalation rule, or whether baseline characteristics differed between groups. As a result, the arm-level adverse-event counts cannot be treated as a randomized comparison or as an estimate of the causal effect of dose.

The safety information is limited. The record lists participant counts and a serious-event term, but does not provide event-level timing, duration, severity distributions, treatment attribution, or details on repeated events. Death counts are not reported in the registry record. The listed denominators apply to the adverse-event summaries; outcome-specific populations for other secondary endpoints are not described.

Other relevant trial details are also absent from the record, including fuller eligibility criteria, treatment administration procedures, missing-data handling, analysis methods, and multiplicity procedures. The registry lists several secondary outcome areas but does not report analyses for them in the registry record for this interpretation. The enrollment of 12 does not by itself establish how many participants contributed data to every outcome.

These limitations do not erase the value of the recorded design and endpoint definitions, but they restrict conclusions to a description of the study plan and posted safety counts. They preclude a robust comparison of regimens or a complete reconstruction of the trial’s analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ixabepilone in Combination With Carboplatin in Patients With Non-small Cell Lung Cancer — NCT00683904.
• Registry record last updated 2016-03-10; status last verified 2016-02.
• Results first posted 2011-04-15.
• 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

NCT00683904 is a completed phase I, non-randomized, unmasked, parallel study of ixabepilone with carboplatin in non-small cell lung cancer as first-line treatment. Enrollment is recorded as 12. The study compared regimens containing ixabepilone 32 mg/m^2 with carboplatin 5 mg/min/mL or 6 mg/min/mL.

The primary endpoint was the participant count with dose-limiting toxicity during days 1 through 21 of Cycle 1, among participants who received at least 1 dose of either study drug. The registry record does not report the primary endpoint result. Adverse-event summaries list 6 participants at risk in each group, with serious-event counts of 1 and 0 and other-event counts of 6 in each group. Superior vena caval occlusion is listed at 16.7%; death counts are not reported in the registry record.

The posted information supports a descriptive account of the design and selected safety counts, not a randomized comparison or a dose-selection conclusion.