Evaluate PKs and Efficacy Assessment of Palifermin in Patients With Sarcoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluate PKs and Efficacy Assessment of Palifermin in Patients With Sarcoma (NCT00267046), a randomized phase 2 study. The primary outcome is Cumulative Incidence Rate of Oral Mucositis.

2. Clinical Question

The study also set out to evaluate palifermin pharmacokinetics and safety with multicycle chemotherapy. Exploratory aims included assessing biologic effects on oral mucosa, investigating potential biomarkers in blood cells, serum, and plasma, and examining whether genetic variation in relevant genes was associated with response. These additional aims do not replace the designated primary outcome measure, and their results are not reported in the registry record.

3. Trial Design

This was a phase II, randomized, double-blind, parallel study sponsored by M.D. Anderson Cancer Center. The registry record lists an enrollment of 49 and a completed status. The recorded start was 2005-12 and primary completion was 2009-07. The record does not state how participants were randomized, whether allocation was concealed, or the allocation ratio.

The comparison was palifermin plus chemotherapy versus placebo plus chemotherapy. Chemotherapy was described as either an Adriamycin (doxorubicin) and ifosfamide regimen (AI) or an Adriamycin and cisplatin regimen (AP). The palifermin description specifies 180 mcg/kg 3 days before chemotherapy. The placebo description specifies a single dose before chemotherapy. The registry lists vincristine and cisplatin among the interventions, but does not provide complete arm descriptions for every chemotherapy component in the record excerpt.

Double masking means the registry characterizes the study as blinded to two parties, but does not identify them or describe how masking was maintained. The parallel model indicates that the study compared groups rather than describing a crossover. The registry does not report the randomization procedure, stratification factors, treatment adherence, or whether the analysis accounted for the two chemotherapy regimens.

The primary outcome timeframe was within 6 blinded cycles, each described as a 3-week cycle, up to 18 weeks. The outcome definition counts participants who developed WHO grade 2 or higher mucositis among participants who completed up to 6 blinded cycles. The stated analysis population is intention to treat. Since the completion-based denominator and intention-to-treat label do not fully explain how participants with incomplete follow-up were handled, the analysis population and denominator cannot be reconstructed from the record alone.

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: Of the 49 enrolled, one participant withdrew before assignment to groups.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention to treat (ITT).

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 Cumulative Incidence Rate of Oral Mucositis, measured over Within 6 blinded cycles (3-week cycles), up to 18 weeks..

The primary outcome is the cumulative incidence of WHO grade 2 or higher oral mucositis during up to 6 blinded chemotherapy cycles, with the timeframe described as up to 18 weeks. The registry defines the measure as the number of participants with grade 2 or higher mucositis divided by the number who completed up to 6 blinded cycles. It labels the outcome unit as a percentage of participants and the summary parameter as a mean, with a 95% confidence interval.

WHO grading distinguishes mucositis by its manifestations and effect on eating. Grade 1 may involve buccal mucosal scalloping or erythema without ulcers, with solid food still swallowed. Grade 2 involves ulcers, with or without erythema, while solid food can still be swallowed. Grade 3 involves ulcers with or without extensive erythema and the ability to swallow liquids but not solid food. Grade 4 is mucositis severe enough that alimentation is not possible. The primary endpoint groups grade 2 and higher, thereby including the moderate-to-severe grades described in the record.

A cumulative proportion over a defined treatment period gives a clinically interpretable account of how often the specified event occurred in the assessed group. It does not, by itself, describe the duration of mucositis or the timing of each episode. The group-specific proportions and confidence intervals are not reported in the registry record, so the endpoint cannot be compared between arms from the record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the confidence interval represent?

The registry specifies a 95% confidence interval for the primary outcome summary. In general, a confidence interval describes the uncertainty associated with an estimate under the method used to calculate it. Its width depends on factors such as the variability in the data and the amount of information available. A confidence interval is not a guarantee that the true value lies inside the particular reported interval, nor does it establish clinical importance on its own. To interpret one, readers need its estimate, both limits, the outcome definition, and the analysis population. The registry record does not report the endpoint estimate or confidence interval limits by group, so neither the magnitude nor the precision of the primary result can be assessed.

How should a cumulative incidence proportion be understood?

The outcome description defines a cumulative incidence as participants who had WHO grade 2 or higher mucositis divided by participants who completed up to 6 blinded cycles. This is a proportion over a stated treatment period. It answers how many assessed participants experienced the event during that period, according to the stated definition. It is not, based on the information in the registry record, a time-to-event estimate or a rate calculated using person-time. The record does not describe how recurrent episodes were counted; the endpoint wording focuses on participants who had the event.

General statistical explanation: proportions can be analyzed or summarized in different ways, and the choice affects the interpretation of estimates and intervals. The registry labels the outcome parameter as a mean and identifies a 95% confidence interval, but does not report the specific calculation method. It would be inappropriate to infer a model, variance estimator, or adjustment procedure from those labels alone.

What does the WHO threshold mean for interpretation?

The endpoint groups WHO grades 2, 3, and 4 under the threshold of grade 2 or higher. The registry's descriptions distinguish the grades by oral findings and the ability to swallow solid food, liquids, or no alimentation. Combining grades gives a binary event definition for the cumulative incidence measure: a participant either met the grade threshold or did not, within the described period. That summary does not preserve differences in severity among participants who crossed the threshold, and it does not report how long symptoms lasted. Those are general consequences of reducing an ordinal severity scale to a threshold outcome; the registry does not report separate grade-specific results.

Why do the analysis population and denominator matter?

The record calls the primary population intention to treat, a general analysis principle that aims to retain participants in the groups to which they were randomized. Yet the endpoint's denominator is described as participants who completed up to 6 blinded cycles. These statements do not establish whether the completed-cycle definition was applied to all randomized participants, whether partial follow-up contributed information, or whether missing assessments were excluded or imputed. The handling of incomplete cycles and missing observations is not reported in the registry record. Without those details and the arm-specific denominators, the endpoint calculation cannot be independently reconstructed.

What can be inferred from the planning assumptions?

The registry describes sample-size planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. These are assumptions for planning illustrations, not necessarily the trial's original design assumptions. The actual planning rationale and sample-size justification are not reported in the registry record. Nor are the illustration values present in the registry record for this analysis. General statistical explanation: a planning calculation asks how much information a future study might need to detect an assumed effect under specified conditions. It is not a measure of the probability that a completed study's finding is true, and it is not observed power. With no reported primary endpoint estimate here, the observed effect underlying the described illustrations cannot be independently evaluated.

The registry also does not report the inferential test for the primary comparison, whether the analysis was adjusted, whether the chemotherapy regimens were analyzed separately, or how any interim analyses were handled. These are not details that can be inferred from the randomized, double-blind, parallel designation. General statistical explanation: estimates and uncertainty are best interpreted in light of a prespecified analysis plan, including how the endpoint, missing data, and multiple outcomes are handled. That plan is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 2 outcome measures and 1 analysis, but the primary endpoint result values are not reported. The study description includes several aims: preliminary efficacy for oral mucositis, pharmacokinetics, safety, and exploratory biological, biomarker, and genetic questions. The registry record does not report a multiplicity adjustment, a hierarchy among outcome tests, or a statistical plan explaining how results across these aims were to be interpreted. It is therefore not possible to determine whether or how the risk of false-positive findings across multiple analyses was addressed.

The stated primary analysis population is intention to treat, while the endpoint definition refers to participants who completed up to 6 blinded cycles. The record does not explain whether the completion requirement changed the analysis population, how participants who discontinued were handled, or what happened when mucositis assessments were unavailable. No missing-data method, imputation approach, sensitivity analysis, or reason for missing observations is reported in the registry record. These omissions matter because a cumulative proportion can depend on who is included in the denominator and how incomplete observation is treated.

The registry does not report whether there were interim analyses, stopping rules, a protocol-specified analysis plan, or a sample-size justification. The planning illustrations described in the record use a two-sided significance level of 0.05, equal allocation, and a normal approximation, but those assumptions do not establish the full analysis plan for the completed trial. Without the endpoint results and analysis details, it is not possible to assess robustness to missing data or multiplicity.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event summary records 0 affected participants among 32 at risk in the palifermin group and 0 among 16 at risk in the placebo group. The deaths field is not populated in the registry record, so deaths are not reported there; an unreported value should not be read as confirmation that no deaths occurred. The record does not list serious adverse-event terms for either group.

For other adverse events, the registry records 31 affected participants among 32 at risk in the palifermin group and 8 among 16 at risk in the placebo group. These are counts of participants recorded as affected, not event counts, and the category is not described by event type, severity, duration, or relationship to study treatment in the available record. The figures therefore do not identify which events occurred or whether the groups differed in particular kinds of harm.

These safety counts should be kept separate from the primary mucositis endpoint. The registry does not establish that its “other adverse events” category corresponds to oral mucositis, nor does it provide enough detail to reconcile the safety summary with the primary endpoint definition. General statistical interpretation: descriptive counts alone do not account for differences in observation time, completeness of reporting, or event severity. They also do not provide a causal estimate. The registry record does not report a formal comparative safety analysis.

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

The registry record supports a description of the trial's design and research question: a randomized, double-blind phase II comparison of palifermin plus chemotherapy with placebo plus chemotherapy in patients with sarcoma. It also specifies a mucositis threshold, a treatment-period window, an intended analysis population, and selected safety counts. These registry entries clarify what the study was designed to investigate, but they are not a report of the primary efficacy findings.

The central limitation is that group-specific cumulative incidence results for WHO grade 2 or higher oral mucositis are not reported in the registry record. There is no endpoint estimate by arm, confidence interval, or between-group effect estimate. As a result, the posted information does not establish the observed frequency of the primary outcome in either group, the direction or size of any difference, or how precisely the comparison was estimated. It cannot support a conclusion about whether the primary outcome differed between the groups.

The safety counts describe recorded participants affected by serious and other adverse events, but the categories are limited and lack details about event types and severity. They do not replace the primary endpoint results and do not, on their own, explain the overall safety profile. Deaths are not reported in the registry record.

The record also does not fully reconcile the intention-to-treat population label with a denominator based on completing up to 6 cycles. It does not explain missing outcome data, analysis methods, multiplicity, or the basis for sample-size planning. Those gaps limit assessment of the reliability and generalizability of any treatment comparison. The trial's aims and design can be described, but conclusions about its primary results or their precision require outcome data and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study raises statistical issues common to randomized trials with repeated treatment cycles and clinically graded outcomes. Its primary endpoint converts the WHO mucositis grades into a threshold event, grade 2 or higher, and summarizes the event cumulatively during up to 6 blinded cycles. That makes the endpoint relatively direct to interpret as an occurrence during a defined treatment period, while omitting information about differences among grades and the duration of episodes.

The denominator deserves attention. The record labels the primary population intention to treat but defines the endpoint using participants who completed up to 6 blinded cycles. Those descriptions do not make clear how participants with incomplete treatment or follow-up were handled. In general, the definition of the analysis population and missing-data method can influence an estimated cumulative proportion, particularly when observation is incomplete. Here, the relevant methods and arm-specific endpoint denominators are not reported.

The study also combines a primary mucositis question with pharmacokinetic and safety aims, plus exploratory biological and genetic investigations. Multiple aims can create multiplicity considerations; the registry record does not report a testing hierarchy or adjustment strategy. Likewise, the record's planning assumptions do not supply a sample-size justification or the numerical illustration values needed to assess precision planning.

Finally, the safety summary shows why descriptive categories need context. Counts of affected participants do not identify specific events, their severity, or their relationship to treatment. Taken together, the record is useful for identifying the intended comparison and endpoint definitions, but the missing efficacy estimates and analysis details prevent a full statistical reading of the trial's primary result.

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 primary endpoint values by treatment group, confidence interval limits, or a between-group effect estimate. This is the key limitation for interpreting the trial's efficacy question. The enrollment listing of 49 does not provide the number analyzed for the primary outcome or its group-specific denominators.

The endpoint definition refers to participants completing up to 6 blinded cycles, whereas the population is identified as intention to treat. The record does not explain how those descriptions align, how participants with incomplete cycles were handled, or how missing mucositis observations were addressed. There is no reported statistical method for the primary comparison, no account of adjustment or stratification, and no indication whether the two chemotherapy regimens were considered separately.

Trial conduct details are also limited. The record does not describe the randomization method, allocation ratio, masking procedures, treatment adherence, or a full protocol. It does not report a sample-size justification, interim analyses, stopping rules, multiplicity procedures, or a statistical analysis plan. These details are necessary to assess how the design and analysis were implemented, rather than infer them from the trial's phase and masking labels.

The safety summary is similarly restricted: serious adverse-event terms are not listed, other adverse events are not broken down by type or severity, and deaths are not reported in the registry record. The available counts therefore cannot provide a comprehensive safety interpretation. The recorded completion status and dates do not resolve these missing outcome and methods details.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluate PKs and Efficacy Assessment of Palifermin in Patients With Sarcoma — NCT00267046.
• Registry record last updated 2012-05-16; status last verified 2012-04.
• Results first posted 2012-05-16.
• 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

NCT00267046 is a completed randomized, double-blind, parallel phase II study sponsored by M.D. Anderson Cancer Center, with an enrollment listing of 49. It compared palifermin plus chemotherapy with placebo plus chemotherapy in patients with sarcoma. The chemotherapy regimens were described as Adriamycin (doxorubicin) with ifosfamide or Adriamycin with cisplatin.

The designated primary outcome was cumulative incidence of WHO grade 2 or higher oral mucositis during up to 6 blinded cycles, described as 3-week cycles and up to 18 weeks. The registry identifies the primary population as intention to treat, while defining the endpoint denominator by completion of up to 6 cycles. Group-specific primary outcome results and analysis details are not reported in the registry record.

The safety summary records serious adverse events and other adverse events by group, but does not provide event terms for the serious category or detailed descriptions of other events. Deaths are not reported in the registry record. The record also lists pharmacokinetic, safety, and exploratory biological aims.