A Phase I/II Clinical Trial of PXD101 in Combination With Doxorubicin in Patients With Soft Tissue Sarcomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase I/II Clinical Trial of PXD101 in Combination With Doxorubicin in Patients With Soft Tissue Sarcomas (NCT00878800), a na phase 1, phase 2 study. The primary outcome is Dose Limiting Toxicity (DLT).

2. Clinical Question

3. Trial Design

This was an open-label, multicentre Phase I/II study of PXD101 in combination with doxorubicin. It is recorded as a single-group trial with no masking and allocation marked not applicable. The registry lists 41 participants enrolled. The study is marked completed; its recorded start is 2006-12 and primary completion is 2012-10.

The stated design began with dose escalation in patients with advanced solid tumours. The combination used a five-day intravenous PXD101 schedule and one day of intravenous doxorubicin, with dose escalation for both drugs described in the arm record. The study summary describes dosing every three weeks. The record does not state the dose units in the arm description, so dose labels should not be interpreted as a particular unit without additional documentation.

Once a maximum tolerated dose was established, the plan allowed an expansion in patients with soft tissue sarcoma to examine safety and efficacy at that dose level. The summary describes a target range of 20-40 patients for that expansion and a stopping condition if no more than 2 responses were observed among the first 20 patients in it. These are design statements, not evidence that the expansion reached its intended size or that the stopping condition was or was not met. That operational history is not reported in the registry record.

The listed cohorts include dose-escalation groups and an MTD expansion group. They are not a randomized comparison, and the registry explicitly cautions that the arms are not a like-for-like control comparison. Cohort membership, treatment sequence, and the purpose of each stage differ, so outcome differences across cohorts would not by themselves isolate a treatment effect. The registry record does not report a detailed statistical analysis plan or a sample-size justification.

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

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 Dose Limiting Toxicity (DLT), measured over Throughout study.

The primary outcome is dose-limiting toxicity of the PXD101 and doxorubicin combination, with the measure identified as a number and the timeframe stated as throughout the study. The registry record does not provide the observed number of dose-limiting toxicities, a participant-level denominator for this outcome, or a definition of which toxicities counted as dose-limiting.

In general, dose-limiting toxicity is used in dose-escalation research to help identify whether adverse effects constrain further increases in a regimen’s dose. It is therefore relevant to a study whose early phase is designed to evaluate safety while escalating doses. The measure is not, by itself, a summary of every adverse event or a direct estimate of benefit. Its interpretation depends on the protocol’s definition, the observation period, and the analysis population; those details are not reported in the registry record beyond the stated study-wide timeframe.

The planned soft tissue sarcoma expansion was also intended to examine efficacy and safety at the maximum tolerated dose. The record lists secondary outcomes including time to response, duration of response, time to progression, disease control rate, and pharmacokinetic measures. However, no observed primary endpoint result is reported in the posted results, so the outcome cannot be quantified from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods that can be described from the record are limited. It identifies a single-group, open-label Phase I/II dose-escalation study and names dose-limiting toxicity as the primary outcome. The record does not report the detailed statistical analysis plan, the definition of a dose-limiting toxicity, or the method used to select or confirm the maximum tolerated dose. These omissions constrain interpretation of both the safety endpoint and the study’s dose-escalation process.

Why does dose escalation affect interpretation?

In general, dose-escalation studies answer questions that differ from the questions addressed by randomized comparisons. Escalating doses is a way to explore tolerability across regimens and to guide selection of a dose for further study. Cohorts may be enrolled at different dose levels or at different stages of the study. They are not necessarily exchangeable groups: dose assignment, enrollment timing, and eligibility or clinical characteristics may differ. As a result, comparing outcome counts across cohorts does not isolate the effect of dose or establish that one regimen is superior.

The record describes a later MTD expansion in soft tissue sarcoma. In general, an expansion can add experience with a selected regimen in a more specific population, but it does not create a randomized control group. The registry summary describes a response-based stopping condition for that expansion. It does not report whether the condition was reached, how response was defined, or how response information was analyzed. These details should not be inferred from the planned rule alone.

What does a count endpoint tell a reader?

The primary measure is specified as a number of dose-limiting toxicities. A count alone does not identify the risk among participants unless the relevant denominator and analysis population are also known. General statistical practice distinguishes an event count from a rate or proportion: a count describes how many events were observed, while a rate or proportion relates events to a defined population or amount of observation. The registry record does not provide the primary count, denominator, or an exposure-based measure, so no such quantity can be interpreted for this endpoint.

The adverse-event summaries give cohort-level counts of participants affected by serious adverse events and other adverse events. Those summaries provide descriptive information, but the record does not state whether repeated events in one person are counted once or separately in these affected-participant figures. Nor does it report duration of exposure or follow-up by cohort. In general, differences in follow-up or exposure can affect observed event counts, so counts alone do not necessarily compare underlying event risk.

How should sample-size planning be read?

In general, sample-size planning depends on a target effect, a chosen significance level, a power target, the design, and assumptions about outcome variability. The planning illustration described for this analysis uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. For time-to-event outcomes, the stated convention is to express the total number of events; for other outcomes, it is participants per arm. These are planning assumptions, not features of the observed single-group study.

The record does not report numerical planning results in the information available for interpretation, and it does not state that the original trial was designed using those assumptions. The planning approach also describes a two-arm equal-allocation setup, whereas this trial is single-group and not a randomized comparison. Such planning illustrations should therefore be treated as hypothetical design exercises, not evidence of the trial’s observed power or a reconstruction of its original design. Sample-size calculations do not establish whether a study’s result is precise; precision depends on the observed data and the analysis.

What is not available about the analyses?

The registry lists 11 outcome measures and zero analyses. It names secondary outcomes covering response timing and duration, progression, disease control, and pharmacokinetic measures, but does not report their numerical results. No model specification, adjustment method, confidence interval, hypothesis-testing result, or analysis population is reported for the primary endpoint. In general, adjusted analyses can account for specified covariates, while unadjusted analyses describe outcomes without such adjustment; neither approach can be attributed to this study without a documented analysis.

For time-to-event outcomes, general interpretation also depends on how time origin, censoring, and event definitions are handled. The record names time to response, duration of response, and time to progression but does not report those analytic details or results. No assumptions should be made about censoring, missing observations, or the statistical tests used. The available record therefore supports explanation of the planned endpoints and design, but not a reproduction or independent evaluation of outcome analyses.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary dose-limiting toxicity measure and secondary measures for response, progression, disease control, and pharmacokinetics. The record does not describe a procedure for controlling multiplicity, such as a hierarchy of tests or an adjustment for evaluating several outcomes. It also lists zero analyses. The registry record therefore does not show whether the secondary measures were formally tested, how results were selected for reporting, or whether any multiplicity strategy was used.

In general, examining multiple outcomes can increase the chance that at least one result appears noteworthy by chance if each is tested separately. A prespecified hierarchy or other adjustment can address that issue, but the appropriate approach depends on the scientific questions and analysis plan. It is not possible to determine from this record whether multiplicity affected any reported inference, because numerical outcome analyses and the relevant plan are not reported.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not specify how participants with incomplete follow-up, unavailable outcome measurements, or treatment discontinuation were handled. It does not identify an intention-to-treat, treated, or evaluable population for the primary outcome or the secondary measures. The study-level enrollment figure does not answer those questions about endpoint-specific denominators.

In general, missing outcomes can affect both the amount of information available and the interpretation of estimates, especially if missingness is related to participant status or treatment experience. Methods such as censoring rules, imputation, or sensitivity analyses need to be specified to assess their implications. None is documented in the registry record, so no assumption about missingness or analysis population can be made.

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: anaemia (33.3%), thrombosis in device (33.3%), haemoglobin decreased (33.3%), pneumonia (33.3%), febrile neutropenia (28.6%).

The serious adverse-event summaries are organized by cohort. The affected counts are 2 of 3 in Cohort 1, 4 of 7 in Cohort 2, 5 of 9 in Cohort 3, 2 of 6 in Cohort 4, and 10 of 16 in the MTD Expansion. These are the cohort-specific counts recorded for participants affected by serious adverse events; they should not be combined into a single comparison, because the cohorts differ in dose level and role in the study.

The record also lists selected serious adverse-event terms with percentages: Anaemia, Thrombosis in device, Haemoglobin decreased, and Pneumonia each at 33.3%; Febrile neutropenia at 28.6%; and Device related infection at 16.7%. The denominator for these percentages is not reported in the registry record. They are not a basis for comparing risk across treatments or for estimating an event rate over time.

In general, serious adverse events are a distinct reporting category and should not be equated with all adverse events or with dose-limiting toxicity. The record also gives counts for other adverse events within each cohort, but does not report event-level detail or clarify the relationship between those counts and repeated events. These summaries describe reported safety experience; without a comparator, exposure information, and fuller outcome definitions, they do not establish comparative safety.

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

The record documents a completed, open-label Phase I/II study of PXD101 with doxorubicin, built around dose escalation and a planned soft tissue sarcoma expansion. It identifies dose-limiting toxicity as the primary outcome and lists safety, response, progression, disease-control, and pharmacokinetic measures. This information clarifies the study’s questions and structure, but the posted results do not provide the observed primary endpoint value or the listed secondary outcome results.

That absence means the registry record cannot show how many dose-limiting toxicities occurred, how the maximum tolerated dose was determined, or what response and progression outcomes were observed. It also cannot establish whether the planned response-based stopping rule was activated. A description of intended methods or endpoints is not itself an outcome finding.

The adverse-event summaries do report affected counts by cohort and selected serious-event terms with percentages. These are descriptive safety observations in groups receiving the combination at different stages or dose levels. Because there is no randomized comparator, and because the cohort summaries do not supply a common comparison framework, they cannot estimate how the combination compares with another treatment. They also do not, on their own, establish the causal contribution of either drug to an event.

In general, a trial’s statistical conclusion depends on the outcome data, the analysis population, and the method used to quantify uncertainty. Here, the record does not report confidence intervals or statistical tests for the primary outcome. It does not provide sufficient information to assess precision for the listed outcomes. The absence of those details is not evidence that an outcome did or did not occur; it limits what can be concluded from this registry record.

The design is relevant as an early clinical investigation of a combination and a dose-selection process. Its findings, if reported elsewhere, would need to be interpreted in light of the nonrandomized, single-group structure and the populations represented in each cohort. No claim that the combination works or does not work follows from the information recorded.

13. Why This Trial Matters Statistically

This trial is statistically notable because it combines dose escalation with a planned disease-specific expansion. Those stages address related but distinct questions: early cohorts explore tolerability across dose levels, while an expansion at the maximum tolerated dose was intended to examine safety and efficacy in soft tissue sarcoma. Recognizing the staged design helps prevent readers from treating all cohorts as if they were parallel treatment groups.

The single-group, open-label structure also illustrates a basic distinction between descriptive safety evidence and comparative evidence. A study can record adverse events and response-related outcomes without including a control arm. However, comparisons among its cohorts cannot provide the same interpretation as a randomized comparison, particularly when doses and cohort purposes differ. This is an important consideration when reading dose-escalation results or cohort-specific summaries.

The endpoint choices reflect different kinds of information. Dose-limiting toxicity is central to dose selection, while response, progression, disease control, and pharmacokinetic outcomes describe other aspects of the planned investigation. In general, each outcome needs an explicit definition and analysis population to support reproducible interpretation. The registry lists these outcome areas but does not report their numerical results or the analysis details needed to evaluate them.

The case also shows why registry design information and posted outcome analyses should be distinguished. A planned stopping rule, named endpoint, or completed status does not establish what was observed. The record supplies useful context for understanding the intended study, but the absence of reported primary and secondary results limits statistical conclusions. Clear outcome reporting, denominators, uncertainty estimates, and analysis methods would be needed for a fuller assessment.

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 registry record does not report the observed result for the primary endpoint, dose-limiting toxicity, or numerical findings for the listed secondary outcomes. The absence of those results prevents evaluation of the study’s principal safety question and the planned response and progression questions. Although the record names 11 outcome measures, it lists zero analyses.

Important design and analysis details are not reported, including the protocol definition of dose-limiting toxicity, the method for establishing the maximum tolerated dose, the endpoint-specific analysis populations, and handling of missing data. The record also does not report a statistical analysis plan, sample-size justification, or details on whether the response-based stopping condition in the expansion was met.

The study has no randomized comparator. Its dose cohorts and MTD expansion are not like-for-like control groups, so between-cohort differences cannot be interpreted as causal treatment effects. The record does not provide a detailed cohort-level description of participant characteristics that would help explain any differences in observed outcomes.

The safety summaries are limited to affected counts by cohort and selected serious adverse-event terms with percentages. The denominator for the term percentages, event-level detail, exposure duration, and follow-up by cohort are not reported. These limitations make it difficult to assess precision or compare safety across cohorts. The study’s completed status and overall enrollment do not resolve these gaps in endpoint reporting or analysis detail.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase I/II Clinical Trial of PXD101 in Combination With Doxorubicin in Patients With Soft Tissue Sarcomas — NCT00878800.
• Registry record last updated 2015-07-28; status last verified 2015-07.
• Results first posted 2014-12-29.
• 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 describes NCT00878800 as a completed, open-label, multicentre Phase I/II, single-group study of PXD101 combined with doxorubicin in patients with advanced solid tumours, followed by a planned soft tissue sarcoma expansion at the maximum tolerated dose. The intervention schedule is described as intravenous PXD101 for five days and intravenous doxorubicin for one day, administered every three weeks. The study enrolled 41 participants.

Dose-limiting toxicity throughout the study is the primary outcome. Listed secondary outcomes include response, progression, disease control, and pharmacokinetic measures. The record reports cohort-level adverse-event summaries and selected serious-event terms, but does not report the observed primary endpoint result, numerical secondary outcome results, or detailed analysis methods. There is no randomized comparator, and cohort differences should not be read as controlled treatment effects.