This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Phase I Combination w/ Epirubicin (NCT00322374), a non-randomized phase 1 study. The primary outcome is Number of Participants With a Dose Limiting Toxicity (DLT).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00322374 |
| Phase | Phase 1 |
| Condition | Metastatic Breast Cancer |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 42 |
| Arms in the primary outcome | n/a |
| Lead sponsor | R-Pharm |
| Results posted | Yes |
2. Clinical Question
Population
Participants with metastatic breast cancer were enrolled. The study lists planned enrollment of 42. The primary endpoint population was described as participants who received at least one dose of both drugs in Cycle 1, completed adequate safety evaluations, and were observed for at least 21 days after the first dose. The registry record’s population description ends mid-sentence, so the complete eligibility wording for this endpoint is not reported in the registry record.
Intervention
Participants received ixabepilone with epirubicin. The registry lists ixabepilone doses of 25 mg/m^2, 30 mg/m^2, or 35 mg/m^2, each combined with epirubicin 75 mg/m^2. Both drugs were administered intravenously on a 21-day cycle; ixabepilone followed epirubicin.
Comparator
There was no randomized control group. The study used a single-group, non-randomized model with three listed dose combinations. These dose cohorts are not a like-for-like control comparison: the registry does not establish that participants in different cohorts were comparable in ways that would support a causal comparison of doses.
Primary question
The primary endpoint asks how many evaluable participants experienced a dose-limiting toxicity during Cycle 1, through Day 21. The registry defines qualifying toxicities as specified blood-count events, other drug-related Grade 3 or Grade 4 non-hematologic toxicity with listed exceptions, or delayed recovery that postpones the next cycle. The observed participant count for this endpoint is not reported in the registry record.
3. Trial Design
This was a Phase I study of ixabepilone in combination with epirubicin in participants with metastatic breast cancer. The registry describes the allocation as non-randomized, the masking as none, and the model as a single group. The listed enrollment is 42, and the study status is completed. The record gives a start date of 2006-08 and a primary completion date of 2009-02.
The regimen descriptions specify three ixabepilone dose levels: 25 mg/m^2, 30 mg/m^2, and 35 mg/m^2. Each was paired with epirubicin 75 mg/m^2. Epirubicin was administered as a 3- to 5-minute intravenous infusion, followed by ixabepilone as a 3-hour intravenous infusion, every 21 days. The record does not report how participants were assigned among the dose levels or the decision rules used to select or escalate doses.
The primary endpoint was the number of participants with a dose-limiting toxicity from baseline through the end of Cycle 1, identified as Day 21. This is a safety-focused endpoint. The record also lists adverse events, serious adverse events, Grade 3/4 adverse events, adverse events leading to discontinuation, and pharmacokinetic measures for both drugs as secondary outcomes. It lists tumor response assessment according to RECIST for evaluable participants, but does not provide response results in the registry record.
General: Phase I studies can investigate tolerability and dose-related safety, but the exact aims and dose-selection procedures of a particular study must come from its record. The registry record does not report a protocol-level dose-selection algorithm, a sample-size justification, or a detailed statistical analysis plan. The design is not a randomized comparison of treatment alternatives, and the three dose cohorts should not be interpreted as randomized arms.
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.
Enrollment
| Stage | Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | All Participants |
|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 42 |
| COMPLETED | 0 | 0 | 0 | 42 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Starting Dose
| Stage | Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | All Participants |
|---|---|---|---|---|
| STARTED | 6 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 0 | 0 | 0 |
Reasons for not completing this period:
| Reason | Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | All Participants |
|---|---|---|---|---|
| Physician Decision | 2 | 0 | 0 | 0 |
| Study Drug Toxicity | 4 | 0 | 0 | 0 |
First Escalation
| Stage | Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | All Participants |
|---|---|---|---|---|
| STARTED | 0 | 30 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 30 | 0 | 0 |
Reasons for not completing this period:
| Reason | Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | All Participants |
|---|---|---|---|---|
| Documented Disease Progression | 0 | 6 | 0 | 0 |
| Physician Decision | 0 | 12 | 0 | 0 |
| Study Drug Toxicity | 0 | 11 | 0 | 0 |
| Participant Request | 0 | 1 | 0 | 0 |
Second Escalation
| Stage | Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | All Participants |
|---|---|---|---|---|
| STARTED | 0 | 0 | 6 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 6 | 0 |
Reasons for not completing this period:
| Reason | Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | All Participants |
|---|---|---|---|---|
| Physician Decision | 0 | 0 | 5 | 0 |
| Study Drug Toxicity | 0 | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The evaluable participant population consisted of participants who met the minimum safety evaluation requirements of the study: participant received ≥1 dose of ixabepilone and epirubicin in Cycle 1, completed adequate safety evaluations, and was observed for ≥21 days following the first dose or the participant experienced DLT.
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.
| Characteristic | Unit | Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | Total |
|---|---|---|---|---|---|
| Participants analysed | 6 | 30 | 6 | 42 | |
| Age, Customized: Between 18 and 65 years | participants | 6 | 24 | 5 | 35 |
| Age, Customized: >=65 years | participants | 0 | 6 | 1 | 7 |
| Age, Continuous | years | 57.5 (48 to 61) | 57.5 (38 to 69) | 53.5 (33 to 68) | 57 (33 to 69) |
| Sex: Female, Male: Female | Participants | 6 | 30 | 6 | 42 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 |
| Region of Enrollment: France | participants | 5 | 16 | 3 | 24 |
| Region of Enrollment: Italy | participants | 1 | 14 | 3 | 18 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With a Dose Limiting Toxicity (DLT), measured over From Baseline to the end of Cycle 1 (Day 21).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with a dose-limiting toxicity during Cycle 1, from baseline through Day 21. It is a count of participants meeting the registry’s toxicity definition, rather than a continuous measure such as a laboratory value or a time-to-event estimate. The record defines a dose-limiting toxicity as a specified treatment-related event involving severe neutropenia or thrombocytopenia, another qualifying drug-related Grade 3 or Grade 4 non-hematologic toxicity, or delayed recovery from treatment-related toxicity that delays the next cycle by at least 3 weeks. The description also lists exceptions for certain toxicities.
The stated safety population required receipt of at least one dose of ixabepilone and epirubicin in Cycle 1, adequate safety evaluations, and observation for at least 21 days after the first dose. The population description is incomplete in the registry record, so its full criteria are not available there. The actual number of participants meeting the endpoint definition is not reported in the registry record.
General: A dose-limiting toxicity endpoint is used to count clinically defined toxicities during a specified early treatment period. A clear definition and observation window matter because the count depends on which events qualify and whether participants had adequate observation. The endpoint can describe the number meeting the definition, but it does not by itself provide a complete account of every safety outcome or establish comparative safety against an untreated or randomized control group.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies dose-limiting toxicity as the primary endpoint, but it does not report the number of participants with a dose-limiting toxicity in the primary endpoint population. Consequently, the posted information does not support a numerical description of the primary endpoint’s observed frequency. It also does not report a confidence interval, hypothesis test, or adjusted estimate for that endpoint. The record lists no analyses. This absence should be read as a lack of reported analysis results, not as evidence that a particular result was zero or that a statistical procedure was performed and found nothing.
The dose groups listed are 25 mg/m^2, 30 mg/m^2, and 35 mg/m^2 of ixabepilone, each with epirubicin 75 mg/m^2. Their adverse-event summaries report participants at risk and participants affected by serious and other adverse events. Those summaries are safety information, not a randomized comparison of dose levels. The registry explicitly describes the study as non-randomized and lists no like-for-like control comparison. Differences between cohorts, if considered, could reflect factors other than dose; the record does not provide an analysis that addresses such differences.
The endpoint definition narrows the primary count to events occurring in Cycle 1 and meeting specified criteria. It includes hematologic thresholds, selected non-hematologic toxicity grades, and delayed recovery. It therefore should not be read as a count of every adverse event over the whole study. Secondary outcomes include broader adverse-event categories and pharmacokinetic measurements, but their numerical results are not reported in the registry record.
General: An estimate describes the observed result, while a confidence interval conveys the uncertainty around an estimate under a specified statistical model. A p-value, when reported, addresses compatibility of data with a statistical null model; it does not establish clinical importance or causality. Neither a confidence interval nor a p-value can be reconstructed for the primary endpoint in the registry record. The registry also does not report a prespecified statistical plan, an interim analysis approach, or a sample-size justification. Those elements should not be inferred from the trial’s Phase I label.
The registry reports tumor response assessment according to RECIST among participants who received at least 2 cycles, had required baseline and on-treatment assessments, and had at least one post-treatment assessment. It does not report the number meeting response criteria or other response results in the record information. Thus, the material supports a description of the study’s design, endpoint definition, and posted safety counts, but not an efficacy conclusion or a quantified primary-endpoint finding.
9. Statistical Methods Explained
What does a participant count represent?
The primary endpoint is a count of participants who met the registry’s definition of dose-limiting toxicity during Cycle 1. This kind of binary outcome classifies each eligible participant as either meeting or not meeting a defined event criterion, then reports the number in the event category. The number is meaningful only alongside its denominator and the rules defining eligibility, event status, and observation time. The registry gives a description of the evaluable population, but its wording ends before the full criterion is complete. It does not report the primary endpoint count or the denominator used in a result.
General: For a binary endpoint, a proportion can summarize the event frequency, and a confidence interval can express sampling uncertainty around an estimate. Such an interval depends on the observed count, denominator, and method. Because the primary endpoint results are not reported in the registry record, neither a proportion nor an interval should be inferred.
Why define the event and time window?
The dose-limiting toxicity definition sets a boundary around which treatment-related events count toward the primary endpoint. The registry includes absolute neutrophil count below 500 cells/mm^3 for at least 7 consecutive days or febrile neutropenia of any duration; Grade 4 thrombocytopenia below 25,000 cells/mm^3 or Grade 3 with bleeding requiring platelet transfusion; other drug-related Grade 3/4 non-hematologic toxicity with stated exceptions; and delayed recovery to Grade 1 or baseline, except for alopecia, when treatment-related toxicity delays the next cycle by at least 3 weeks.
The endpoint’s timeframe is baseline through the end of Cycle 1 (Day 21). Events outside that period do not fall within this primary endpoint definition, although other outcomes may capture safety over a broader period. General: Limiting an endpoint to a defined window can make the question more focused, but it also means the endpoint does not summarize all later toxicity. Adequate observation is important: a participant who is not observed for the required period may not have the same opportunity for an event to be recorded.
What can the design support?
The study is described as non-randomized and single-group, with no masking. Its three listed dose combinations are not randomized control groups. General: Randomization helps balance measured and unmeasured prognostic factors on average, whereas non-randomized groups may differ for reasons other than treatment dose. Without a randomized comparison or a reported adjustment strategy, a numerical contrast between the dose cohorts should not be treated as an estimate of a causal dose effect. The registry does not report an adjustment model or comparative statistical analysis.
The design can be described in terms of the regimens administered and the safety observations reported. The record does not provide the procedures for assigning participants to dose levels, dose-escalation decisions, or rules for selecting a recommended dose. These details should not be reconstructed from the dose groups alone.
How should uncertainty and significance be understood?
General: A confidence interval is a range produced by a statistical procedure that reflects uncertainty in an estimate under the method’s assumptions. A narrow interval generally indicates greater precision than a wide interval, but precision does not establish that a result is clinically important. A hypothesis test compares data with a stated null model and produces a p-value under specified assumptions. A p-value is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect.
No confidence interval, p-value, or inferential analysis for the primary endpoint is reported in the registry record. No analysis results are listed. The sample-size assumptions describe a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with an effect defined as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial itself used that design or that a particular power was observed. Sample-size calculations are not observed power, and no resulting sample-size values are included in the registry record for this analysis.
Why can over-dispersion matter?
General: Over-dispersion occurs when count data vary more than a chosen statistical model expects. If it is ignored, model-based standard errors and confidence intervals may be too small, making results appear more precise than warranted. It is relevant only when a count model and its assumptions are appropriate; it does not create a result where no endpoint count or analysis is reported. The registry’s primary endpoint is presented as a participant count, and the record does not report a model for that count or an assessment of over-dispersion.
What is known about multiplicity?
The registry lists 16 outcome measures, including the primary dose-limiting toxicity endpoint, adverse-event outcomes, pharmacokinetic measures, and tumor response assessment. Listing multiple outcomes does not tell readers whether formal hypothesis tests were planned, which outcomes were tested, or how any multiplicity was handled. The registry record does not report a multiplicity adjustment, a testing hierarchy, or an analysis plan. General: When several hypotheses are tested, the chance of at least one false-positive result can increase unless the analysis accounts for the testing strategy. That general concern does not establish that confirmatory tests were performed in this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 16 outcome measures, but it does not report a statistical analysis plan describing how those outcomes were analyzed or prioritized beyond identifying dose-limiting toxicity as primary. A multiplicity strategy, such as a testing hierarchy or adjustment across hypotheses, is not reported in the registry record. The record lists no analyses, so it does not provide a set of inferential results from which to assess how multiple testing was handled. The absence of a reported approach is not evidence that a particular method was used or that multiplicity was irrelevant.
The primary endpoint population is described as requiring at least one dose of both drugs in Cycle 1, adequate safety evaluations, and at least 21 days of observation following the first dose. The population description ends mid-sentence. The full eligibility wording, numbers excluded from the endpoint analysis, and reasons for exclusion are not reported in the registry record. Although the brief summary describes criteria for tumor response evaluability, the number of participants meeting those criteria and the handling of missing response assessments are not reported in the record information.
Missing outcome data can affect both the denominator and the interpretation of an observed count. General: Complete-case analysis, imputation, and sensitivity analysis are different approaches to incomplete data, and their suitability depends on why observations are missing and on the analysis goal. The registry record does not report which approach, if any, was used for the primary endpoint or secondary outcomes. It also does not report an interim analysis plan or a sample-size justification. Those omissions limit evaluation of the planned analysis and its robustness; they do not establish that data were missing or that an interim analysis occurred.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | 2 | 6 | 33.3% |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | 8 | 30 | 26.7% |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | 1 | 6 | 16.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | 6 of 6 |
| Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | 30 of 30 |
| Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 |
|---|---|---|---|---|
| NAUSEA | Gastrointestinal disorders | 0 of 6 | 2 of 30 | 0 of 6 |
| FEBRILE BONE MARROW APLASIA | Blood and lymphatic system disorders | 0 of 6 | 2 of 30 | 0 of 6 |
| PYREXIA | General disorders | 0 of 6 | 2 of 30 | 0 of 6 |
| PLATELET COUNT DECREASED | Investigations | 0 of 6 | 0 of 30 | 1 of 6 |
| HYPERSENSITIVITY | Immune system disorders | 1 of 6 | 0 of 30 | 0 of 6 |
| SYNCOPE | Nervous system disorders | 0 of 6 | 0 of 30 | 1 of 6 |
| CEREBROVASCULAR ACCIDENT | Nervous system disorders | 0 of 6 | 1 of 30 | 0 of 6 |
| VOMITING | Gastrointestinal disorders | 1 of 6 | 0 of 30 | 0 of 6 |
| ANAEMIA | Blood and lymphatic system disorders | 0 of 6 | 1 of 30 | 0 of 6 |
| NEUTROPENIA | Blood and lymphatic system disorders | 0 of 6 | 0 of 30 | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2 | Ixabepilone 35 mg^m2 + Epirubicin 75 mg^m2 |
|---|---|---|---|---|
| NEUTROPENIA | Blood and lymphatic system disorders | 6 of 6 | 30 of 30 | 6 of 6 |
| NAUSEA | Gastrointestinal disorders | 5 of 6 | 25 of 30 | 4 of 6 |
| ALOPECIA | Skin and subcutaneous tissue disorders | 6 of 6 | 21 of 30 | 6 of 6 |
| VOMITING | Gastrointestinal disorders | 3 of 6 | 21 of 30 | 4 of 6 |
| ANAEMIA | Blood and lymphatic system disorders | 5 of 6 | 20 of 30 | 3 of 6 |
| PARAESTHESIA | Nervous system disorders | 5 of 6 | 15 of 30 | 3 of 6 |
| ASTHENIA | General disorders | 4 of 6 | 16 of 30 | 2 of 6 |
| LEUKOPENIA | Blood and lymphatic system disorders | 3 of 6 | 11 of 30 | 3 of 6 |
| HYPOREFLEXIA | Nervous system disorders | 3 of 6 | 10 of 30 | 2 of 6 |
| MYALGIA | Musculoskeletal and connective tissue disorders | 0 of 6 | 11 of 30 | 4 of 6 |
Serious events with the highest arm-level rate: platelet count decreased (16.7%), hypersensitivity (16.7%), syncope (16.7%), vomiting (16.7%), neutropenia (16.7%).
The registry’s adverse-event summary gives three dose groups. For ixabepilone 25 mg/m^2 with epirubicin 75 mg/m^2, it reports 6 participants at risk and 2 affected by serious adverse events; the corresponding other-adverse-event count is 6 at risk and 6 affected. For ixabepilone 30 mg/m^2 with epirubicin 75 mg/m^2, it reports 30 at risk and 8 affected by serious adverse events, and 30 at risk and 30 affected by other adverse events. For ixabepilone 35 mg/m^2 with epirubicin 75 mg/m^2, it reports 6 at risk and 1 affected by serious adverse events, and 6 at risk and 6 affected by other adverse events.
The listed serious-event terms include platelet count decreased, hypersensitivity, syncope, vomiting, and neutropenia, each at 16.7%, and nausea at 6.7%. The registry record does not establish in this summary whether these percentages are participant-level rates, event-level rates, or how terms may overlap. Death counts are not reported in the registry record.
General: “At risk” identifies the group size used in the adverse-event listing; “affected” is the number of participants recorded in that category. Serious events and other adverse events are distinct categories in this summary. These counts do not establish that a particular regimen caused an event, nor do they support a causal comparison across the non-randomized dose groups.
12. What the Result Does, and Does Not, Mean
The record establishes that this completed Phase I study evaluated ixabepilone combined with epirubicin in metastatic breast cancer, using three listed ixabepilone dose levels with epirubicin held at 75 mg/m^2. It identifies dose-limiting toxicity through Cycle 1 as the primary endpoint and provides its event criteria and a description of the evaluable population. The posted safety summary also reports counts of participants affected by serious and other adverse events in each dose group.
However, the number of participants meeting the primary dose-limiting toxicity definition is not reported in the registry record. The record also does not report a confidence interval or a statistical test for that endpoint. Tumor response assessment is described for evaluable participants using RECIST, but response results are not reported in the record information. Pharmacokinetic measures are listed as secondary outcomes, without numerical results in the registry record for this analysis.
General: An endpoint definition explains what would count as an event; it is not itself an observed result. A safety count can describe what was recorded in a defined group, but it does not prove causation. In a non-randomized study, differences between dose cohorts can be influenced by differences in who entered each cohort or how they were followed. The registry does not report a randomized control arm or a comparative adjustment that would resolve this concern.
The study’s design and posted event counts therefore support a descriptive account of the recorded regimens and safety information. They do not support a conclusion about comparative treatment effects, a quantified dose-limiting toxicity rate, or tumor response. A missing result should not be interpreted as zero events or as evidence of no effect. The registry record also does not report the dose-selection rules, complete analysis plan, or rationale for sample size, so these aspects cannot be inferred from the listed design and outcomes.
13. Why This Trial Matters Statistically
This study illustrates why the endpoint definition, analysis population, and result must be considered together. Dose-limiting toxicity is not simply any adverse event: the registry specifies qualifying event types, severity thresholds, treatment relationship, and an early observation window. The endpoint population also has stated safety-evaluation and observation requirements. These details determine which participants and events belong in the primary count.
The record also shows the limits of reading dose cohorts as if they were controlled arms. Although three ixabepilone dose levels are listed, the study is non-randomized and single-group. The groups can be described separately, but their results do not constitute a randomized dose comparison. Without assignment details, a comparative analysis, or adjustment information, the record cannot isolate dose as the reason for any difference between cohorts.
There is an important distinction between a registered endpoint and a reported endpoint result. The registry identifies dose-limiting toxicity as primary, yet the participant count and inferential analysis are not reported. Likewise, secondary outcomes and RECIST assessment are listed without corresponding numerical results in the record information. An outcome’s presence in a registry entry does not establish that its result is available.
General: Statistical interpretation depends on transparent denominators, complete outcome reporting, uncertainty estimates, and a clearly specified analysis strategy. Without those elements, readers can characterize design and event listings but cannot evaluate precision or draw a well-supported comparative conclusion. This distinction is especially important in early-phase, non-randomized research, where descriptive safety observations and causal evidence answer different questions.
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 primary endpoint result is not reported in the registry record. Without the number of participants with dose-limiting toxicity and the analyzed denominator, the event frequency and its precision cannot be evaluated. The population description is also incomplete, ending after the observation requirement with unfinished wording. Full eligibility criteria for the endpoint population are therefore not reported in the registry record.
The design is non-randomized, unmasked, and described as a single group. The three dose combinations do not provide a randomized control comparison. The registry record does not report how dose cohorts were assigned, whether cohort characteristics differed, or whether any method was used to adjust comparisons. Consequently, the listed event counts should be interpreted descriptively rather than causally.
The record lists adverse-event counts, but does not report death counts. It provides serious-event terms and percentages without enough detail in the described information to determine whether percentages refer to people or events, or how overlapping terms were handled. The record’s secondary outcomes include pharmacokinetic measures and tumor response assessment, but the corresponding numerical results are not reported in the registry information.
The record does not report a detailed statistical analysis plan, multiplicity approach, interim analysis strategy, or sample-size justification. It also does not report the handling of missing outcome data or the number and reasons for exclusions from endpoint populations. The listed planning assumptions do not establish the study’s own design rationale or observed power. These reporting gaps limit assessment of the endpoint analysis, precision, and robustness.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase I Combination w/ Epirubicin — NCT00322374.
- Registry record last updated 2016-03-10; status last verified 2016-02.
- Results first posted 2010-08-10.
- 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.
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18. Record Summary
The registry record describes NCT00322374, a completed Phase I study titled “A Phase I Study of Ixabepilone in Combination With Epirubicin in Patients With Metastatic Breast Cancer.” It lists R-Pharm as sponsor, planned enrollment of 42, and a non-randomized, unmasked, single-group design.
The regimens paired ixabepilone 25 mg/m^2, 30 mg/m^2, or 35 mg/m^2 with epirubicin 75 mg/m^2 every 21 days. The primary endpoint was the number of participants with a dose-limiting toxicity through the end of Cycle 1 (Day 21). Adverse-event outcomes, pharmacokinetic measures, and tumor response assessment were also listed.
The record includes serious and other adverse-event counts by dose group. It does not report the primary endpoint count, a statistical analysis for that endpoint, or numerical tumor response results in the registry information. The full primary endpoint population wording is incomplete in the record.