Adjuvant Radiation Therapy With Ifosfamide in Patients With Mixed Mesodermal Tumors of the Uterus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adjuvant Radiation Therapy With Ifosfamide in Patients With Mixed Mesodermal Tumors of the Uterus (NCT00231842), a na phase 2 study. The primary outcome is Cycles With Hematologic Toxicities.

2. Clinical Question

The clinical rationale in the registry record is that the optimal sequence or modality for adjuvant treatment of mixed mesodermal tumors remains to be established. The proposed approach was to sandwich pelvic radiation with chemotherapy, with the stated aim of reducing distant metastasis and both local and distant recurrence. The record also presents improved progression-free interval and possibly extended survival as hoped-for consequences, not as demonstrated findings.

Statistically, the main question available from the record is descriptive: how many cycles were associated with severe hematologic toxicity during this regimen? The record does not report the actual cycle count for the primary measure. It therefore does not establish the frequency of those toxicities from this endpoint, nor does it provide a comparative estimate of benefit or harm against another strategy. The enrollment listed is 30, but the number of participants contributing to the primary endpoint is not reported in the registry record.

3. Trial Design

This was a completed phase II pilot trial sponsored by Montefiore Medical Center. The listed study period began in 2003-02, and primary completion was 2011-07. Enrollment is recorded as 30. The registry identifies a single-group model, allocation as not applicable, and no masking. These features describe a study without a randomized between-group treatment contrast.

The eligible population described in the treatment arm was participants with surgically staged carcinosarcoma and no gross residual disease. The regimen description says participants were initially administered ifosfamide and cisplatin every 3 weeks for 3 cycles, followed by pelvic external beam radiation and brachytherapy, then followed by 3 additional c… The final portion of that arm description is truncated in the registry record. The study rationale describes radiation as being sandwiched between chemotherapy; the interventions listed are ifosfamide, radiation therapy and cisplatin.

The registry identifies the study as phase II and pilot. Those labels place the trial in an exploratory treatment-evaluation context, but the record does not report a protocol rationale for sample size, a prespecified statistical analysis plan, or interim-analysis procedures. The study’s single-group design means any outcome description concerns participants treated under the study regimen; it cannot by itself separate treatment effects from the natural course of disease, participant selection or other factors. No control arm is listed against which recurrence, survival or toxicity could be compared.

The primary outcome is described as a count of cycles with grade 3 or grade 4 hematologic toxicities, with a timeframe of 2 years. The registry reports that 138 cycles were administered out of 162 planned cycles, stated as 85%. That treatment-delivery information is distinct from the primary toxicity count: the actual number of cycles with the specified toxicities is 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.

Before assignment: 30 participants were enrolled and 3 participants withdrew prior to therapy. Twenty-seven participants received the first three cycles of chemotherapy and Radiation Therapy and were included in the analysis.

Overall Study

Reasons for not completing this period:

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 Cycles With Hematologic Toxicities, measured over 2 years.

The primary endpoint is titled “Cycles With Hematologic Toxicities.” Its unit is cycles, and the description concerns the number of cycles during which participants experienced grade 3 or grade 4 hematologic toxicities. The timeframe is 2 years. The registry also states that most toxicities were self-limiting, but does not provide the numerical endpoint result or details identifying the specific hematologic events counted for this measure.

A cycle-based measure can describe how often treatment cycles coincide with specified toxicities. It differs from a participant-based measure: one participant may receive more than one cycle, so a cycle count does not directly state how many people experienced toxicity. It also does not, on its own, describe duration, severity within the stated grades, or whether a participant’s treatment was changed. Those interpretations require additional definitions and results, which are not reported in the registry record.

Such an endpoint can be useful when assessing the tolerability of a regimen delivered over repeated treatment cycles. Counts of affected cycles can communicate treatment burden in relation to treatment delivered. The registry reports that 138 cycles were administered out of 162 planned cycles (85%), which provides context about delivery, but it does not give the number of those cycles with grade 3 or grade 4 hematologic toxicity. A rate, comparison, or estimate of precision for the primary endpoint therefore cannot be read from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting a clinical trial begins with identifying the design and the unit of analysis. This record describes a single-group phase II pilot, with no masking and allocation marked not applicable. In general, random assignment to a comparison group helps balance measured and unmeasured characteristics between treatment strategies. A single-group study does not create that comparison. It can describe what happened among participants receiving the regimen, but observed outcomes alone cannot show what would have happened under a different treatment strategy.

What does a cycle count represent?

The primary measure uses treatment cycles as its unit. In general, a count endpoint records how many events or units meet a stated definition. Here, the stated definition concerns cycles during which participants experienced grade 3 or grade 4 hematologic toxicities. A count needs an interpretable denominator: readers need to know the number of cycles assessed and how the toxicity definition was applied. The registry reports 138 administered cycles out of 162 planned cycles (85%), but it does not report the number of cycles with the primary toxicity outcome. Those delivery totals do not supply the missing event count.

Repeated cycles from the same participant are not necessarily statistically independent. In general, a participant’s prior toxicity, treatment exposure or clinical course may relate to later cycles. If a study analyzes cycle counts, an analysis may need to account for this clustering; otherwise, uncertainty can be understated. This is a general statistical consideration, not a description of the method used in this trial. The analysis method for the primary outcome is not reported in the registry record.

Why can count outcomes vary more than expected?

In general, count data are often analyzed with methods suited to nonnegative event counts. Some models assume that the variability in counts follows a particular relationship to the average. Over-dispersion occurs when the observed variability exceeds that assumption. Ignoring over-dispersion can make confidence intervals too narrow and tests too optimistic. Repeated observations within a participant can also contribute to extra variability. These considerations explain why an analysis plan should identify the count model and how within-participant dependence is handled. The registry record does not report a model, an over-dispersion assessment or an adjustment for repeated cycles.

A confidence interval, in general, describes the precision of an estimated quantity under the assumptions of the statistical method used. It does not remove design limitations, and it does not turn an observational contrast into a randomized one. The registry record does not report a confidence interval for the primary endpoint, and it provides no endpoint estimate from which readers could assess precision.

What do the planning illustrations mean?

The registry’s planning assumptions describe an illustration based on the observed effect, using a two-sided significance level of 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. These are planning assumptions, not evidence that the single-group trial included a two-arm comparison. They also do not represent observed power. A planned sample size is a design calculation about the information a future study might need under specified assumptions; it is not a measure of the probability that this completed trial’s findings are true.

The planning description distinguishes time-to-event calculations, which use a total number of events, from other calculations, which use participants per arm. No actual planning values are included in the registry entries available for this analysis. The trial’s enrollment of 30 should not be conflated with an illustration for a future two-arm study. The assumptions or justification used to choose this trial’s enrollment are not reported in the registry record.

How should the safety counts be interpreted?

Adverse-event counts depend on the event definitions, period of observation, and whether the count refers to events or affected participants. The record lists a group titled “Chemotherapy and Radiation Therapy,” 27 at risk, 13 in the serious affected count, 0 in the other affected count and 0 deaths. Neutropenia is listed at 48.1% among the leading serious terms. The record does not provide details sufficient to reconstruct how these categories were derived or to map them onto the primary endpoint. These adverse-event counts describe reported safety information; without a comparator, they do not establish excess risk attributable to the regimen.

Statistical interpretation should therefore keep distinct the treatment-delivery count, the cycle-based primary endpoint, and the adverse-event counts. Each has a different unit or definition. The registry record does not report an analysis plan that reconciles those measures, and no analysis results are listed.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns the risk of misleading findings when several outcomes or comparisons are tested. A prespecified primary outcome and a documented approach to secondary outcomes help readers understand which results were confirmatory and how statistical error was handled. The registry lists one outcome measure, the cycle count for hematologic toxicities, but a formal multiplicity strategy is not reported in the registry record. No statistical tests or analysis results are listed, so it is not possible to assess whether any adjustment was used.

Missing-data handling is also not described. The record reports that 138 cycles were administered out of 162 planned cycles (85%), but does not report why the remaining planned cycles were not administered, whether toxicity data were available for every administered cycle, or how incomplete observations were treated. These details matter because the primary measure is cycle-based: missing toxicity information could affect both the count and its denominator.

The analysis population for the primary outcome is not reported in the registry record. Enrollment is listed as 30, while the adverse-event grouping lists 27 at risk. The record does not explain the relationship between these counts or identify which participants contributed to the primary endpoint. It also does not state whether the analysis followed all enrolled participants, a treated population or another defined group. No assumptions about missing outcomes, exclusions, or participant-level follow-up should be inferred from the listed totals.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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

Serious events with the highest arm-level rate: neutropenia (48.1%).

The registry lists a “Chemotherapy and Radiation Therapy” adverse-event group with 27 at risk. Its serious adverse-event affected count is 13; the other adverse-event affected count is 0; and deaths are listed as 0. Neutropenia appears among the leading serious terms, at 48.1%. These are registry safety entries, separate from the primary endpoint’s cycle-based measure of grade 3 and grade 4 hematologic toxicity.

The terms “serious” and “grade 3 or grade 4” are not interchangeable. Seriousness generally describes regulatory or clinical consequences of an event, whereas grading describes severity; an event can be classified along both dimensions. The registry record does not provide enough detail to determine how its serious-event categories overlap with the primary endpoint. The 48.1% entry should be read as the reported proportion attached to the listed serious term, not as a primary-endpoint rate.

These counts do not establish comparative safety because the study is single-group and no control group is listed. The registry record does not report event-level details, timing, duration, or the method used to summarize recurrent events. The zero entries should therefore be understood as the recorded counts in those categories, not as proof that no unrecorded events occurred.

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

The registry record describes a pilot evaluation of adjuvant ifosfamide-based chemotherapy with pelvic radiation for surgically staged carcinosarcoma without gross residual disease. Its stated rationale was to sandwich radiation with chemotherapy in an effort to reduce recurrence. That rationale explains why the sequence was proposed; it does not demonstrate that recurrence was reduced.

The record reports that 138 cycles were administered out of 162 planned cycles (85%). It also lists safety counts for the chemotherapy and radiation group, including 13 in the serious affected count among 27 at risk and 0 deaths. Neutropenia is listed at 48.1% among the leading serious terms. These findings describe treatment delivery and recorded adverse events. The primary outcome’s numerical result—the number of cycles with grade 3 or grade 4 hematologic toxicity—is not reported in the registry record.

Because there is no randomized comparator, the study cannot establish that this regimen is more or less effective or safer than another strategy. The information also does not establish an effect on local recurrence, distant recurrence, progression-free interval or survival. Those outcomes appear in the study rationale, but no numerical results for them are included in the registry entries available for this analysis.

The record is therefore most informative as a description of a single-group pilot regimen and its recorded delivery and safety information. It does not support a precise estimate of the primary toxicity outcome, and it does not provide evidence for a comparative treatment effect. Further interpretation would require complete endpoint results, definitions, analysis methods and outcome follow-up; those details are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why a treatment rationale, a study design and a reported outcome must be read separately. The rationale proposes a sequence intended to address local and distant recurrence. The design is single-group, so it can describe experience under that sequence but does not offer a randomized counterfactual. The distinction matters whenever a study’s stated hope is stronger than the comparison its design can support.

The primary endpoint also illustrates the importance of matching the unit of measurement to the question. A count of cycles with hematologic toxicity is not the same as the proportion of participants who experienced toxicity. Repeated cycles can contribute multiple observations from one participant, and any statistical analysis must consider that structure. Here, the record gives a cycle-delivery total but not the count for the primary endpoint, leaving the central toxicity measure unquantified.

Safety summaries add another lesson: serious-event counts, adverse-event counts and toxicity grades are related but distinct descriptions. The listing of neutropenia and serious-event counts offers useful safety context, but does not fill in the missing cycle-based endpoint or provide a comparison with another regimen.

Finally, planning calculations should not be mistaken for trial results. The registry describes assumptions for planning illustrations, including a two-arm design, while the trial itself is listed as single-group. Keeping those contexts distinct prevents a hypothetical future-study calculation from being interpreted as evidence about the completed trial.

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 central limitation in the registry record is that the primary endpoint is described but its numerical result is not reported. The record says the measure counts cycles with grade 3 and grade 4 hematologic toxicities, but gives no count for that outcome. Without it, the endpoint cannot be quantified or assessed for precision.

The single-group design has no randomized comparator listed. As a result, the study cannot provide a controlled estimate of the regimen’s effect on toxicity, recurrence or survival. The registry’s stated goals concerning recurrence and possible survival benefit should not be read as findings. The analysis method, statistical plan, interim analyses and sample-size justification are not reported in the registry record.

Some treatment and follow-up details are also incomplete. The arm description is truncated after the reference to 3 additional c…, and the record does not report why 138 cycles were administered out of 162 planned cycles (85%). It does not specify the primary-endpoint analysis population, the completeness of toxicity observations, or how missing cycle data were handled. Although 30 participants are listed as enrolled and 27 as at risk in the adverse-event group, the relationship between those counts is not explained.

The adverse-event listing is limited to group-level counts and the leading serious term. Event-level timing, duration and overlap with the primary endpoint are not reported in the registry record. These gaps constrain interpretation of both treatment delivery and safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Adjuvant Radiation Therapy With Ifosfamide in Patients With Mixed Mesodermal Tumors of the Uterus — NCT00231842.
• Registry record last updated 2019-01-23; status last verified 2019-01.
• Results first posted 2019-01-23.
• 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

NCT00231842 is a completed phase II pilot trial sponsored by Montefiore Medical Center. The study began in 2003-02, primary completion was 2011-07, and enrollment is listed as 30. It examined a single-group adjuvant sequence involving ifosfamide, cisplatin and radiation therapy for mixed mesodermal tumors of the uterus.

The primary outcome was cycles with hematologic toxicities over 2 years, defined in the description as cycles during which participants experienced grade 3 or grade 4 toxicities. The record reports 138 cycles administered out of 162 planned cycles (85%), but does not report the primary endpoint count. Safety entries list 27 at risk, 13 in the serious affected count, 0 in the other affected count and 0 deaths; neutropenia is listed at 48.1% among the leading serious terms.

The single-group design does not provide a randomized comparison. The registry record does not report an analysis plan or numerical result for the primary endpoint.