Study to Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors (NCT01962103), a non-randomized phase 1, phase 2 study. The primary outcome is Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

This was a multicenter, open-label Phase 1/2 study of nab-paclitaxel in pediatric patients and young adults with recurrent or refractory solid tumors. The registry lists the study as completed and records enrollment of 107 participants. The listed study start was 2013-12-04, and the primary completion date was 2017-12-05. Those dates describe the registered study timeline; they do not supply outcome results.

Phase 1 was dose-finding. The registry lists cohorts at 120 mg/m^2, 150 mg/m^2, 180 mg/m^2, 210 mg/m^2, 240 mg/m^2, and 270 mg/m^2. Nab-paclitaxel was administered intravenously on Days 1, 8 and 15 of a 28-day cycle. The stated Phase 1 objective was to establish the RP2D. The specific dose-escalation or dose-selection algorithm, including how decisions between cohorts were made, is not reported in the registry record.

Phase 2 enrolled participants with Ewing's sarcoma, neuroblastoma, or rhabdomyosarcoma at the RP2D. The listed dose was 240 mg/m^2 for participants weighing > 10 kg and 11.5 mg/kg for participants weighing ≤ 10 kg, on the same weekly schedule within a 28-day cycle. The record describes continuation until disease progression, death, withdrawal of consent, or unacceptable toxicity.

Allocation was nonrandomized, masking was none, and the model was single group. The dose cohorts were not randomized controls, and the record does not describe a concurrent comparator. Phase 1's primary endpoint was the count of participants with DLTs. Secondary outcomes listed for Phase 1 included objective response rate and pharmacokinetic measures, such as plasma concentration, area under the concentration-time curve, clearance, and volume of distribution. Numerical results for these outcomes are 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: Sixty-five participants were included in the Phase 1 enrolled population, and 64 enrolled partcipants received at least 1 dose of study drug and were included in the safety population, noted below. Forty-two participants were included in the Phase 2 enrolled and safety populations.

Only the first 6 of 9 groups are shown.

Phase 1

Reasons for not completing this period:

Phase 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Dose Determining Set (DDS): all Phase 1 participants who received all 3 weekly doses of nab-paclitaxel at the cohort planned dose during Cycle 1 and had adequate safety assessments during the DLT assessment period or experienced a DLT. The DDS did not include participants who were enrolled at each dose once the dose had been determined to be safe.

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.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs), measured over DLT assessment period: For participants > 10 kg: the first 28-day cycle including Cycle 2 Day 1 predose evaluations; for participants ≤ 10 kg: the first two 28-day cycles including Cycle 3 Day 1 predose evaluations.

The primary Phase 1 endpoint is the number of participants with dose-limiting toxicities during a defined assessment period. It is a count of participants meeting the DLT definition, rather than a measure of tumor response or a comparison with another treatment. The assessment period differed by weight: for participants > 10 kg, it covered the first 28-day cycle, including Cycle 2 Day 1 predose evaluations; for participants ≤ 10 kg, it covered the first two 28-day cycles, including Cycle 3 Day 1 predose evaluations.

The registry defines a DLT as an investigational product-related adverse event during that period that caused treatment discontinuation or met one of several criteria. These included specified Grade 3 or 4 nonhematologic toxicities, persistent severe nausea or vomiting despite maximal anti-emetic treatment, certain prolonged blood-count toxicities, febrile neutropenia with confirmed bacterial infection, and a delay in treatment due to Grade 3 hematologic toxicity. The definition also lists exceptions and duration thresholds.

In general, a DLT count is used in dose-finding because it records how many participants experienced prespecified toxicities at a dose. It can inform dose selection when interpreted with the dose level, assessment rules, and population actually evaluated. The registry record describes a Dose Determining Set (DDS) but does not report the DLT count or the full population description. As a result, the primary endpoint's observed value and its precision cannot be assessed from the posted record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study combines dose-finding with a later phase focused on preliminary clinical activity. In general, dose-finding studies examine safety at planned dose levels to help select a dose for subsequent evaluation. The registry lists six Phase 1 dose cohorts and states that the objective was to establish the RP2D. It does not report the dose-escalation algorithm, cohort assignment rules, or decision thresholds. Those details should not be inferred from the dose list alone.

What does the primary endpoint count?

The primary endpoint is a participant count: the number of participants with a DLT. A binary outcome records whether each participant did or did not meet the DLT definition during the relevant assessment period. A count can be interpreted only alongside its denominator and the criteria used to decide who was evaluable. The registry gives the definition and describes the Dose Determining Set, but the DLT result and the size of that set are not reported in the registry record.

The endpoint's definition is clinically and statistically consequential. It includes events that lead to treatment discontinuation and several toxicity criteria with grade, duration, or treatment requirements. A DLT count therefore depends on applying these rules consistently and on observing participants over the specified period. The assessment window is not identical for the two weight categories: the record specifies a first-cycle window for participants > 10 kg and a two-cycle window for participants ≤ 10 kg. The number assessed under each window is not reported.

Why is the design not a controlled comparison?

In general, random assignment helps make treatment groups comparable by reducing systematic differences in who receives each treatment. This study was nonrandomized and single group, with no masking and no separate control group. Participants received nab-paclitaxel at planned dose levels in Phase 1 or at the RP2D in Phase 2. Thus, comparisons between dose cohorts or tumor groups are not equivalent to a randomized treatment comparison. Differences in observed counts could reflect differences in cohort composition, dose, or follow-up as well as treatment exposure; the posted data do not isolate these explanations.

Open-label means treatment assignment was not masked. The registry does not report whether outcome assessments used independent review or any other procedures to reduce assessment bias. Such procedures should not be assumed.

What can a confidence interval tell a reader?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity, such as an event proportion. A narrower interval indicates greater precision under the assumptions of the method; a wider interval indicates more uncertainty. It does not fix limitations in the study design or show that an observed association is causal. No confidence interval for the primary endpoint or response outcomes is reported in the registry record, so their precision cannot be evaluated.

For a binary endpoint, an analysis would ordinarily need the number meeting the definition and the number evaluated. Reporting only total enrollment would not supply the denominator if the endpoint population differs from the enrolled population. The registry defines the DDS as Phase 1 participants who received all three weekly doses at the cohort planned dose during Cycle 1 and had adequate safety assessments during the DLT period or experienced a DLT. The remainder of the population description is incomplete in the registry record, and the DDS size and DLT count are not reported.

How should the sample-size illustrations be understood?

In general, a planning calculation estimates the sample size needed for a specified statistical objective under stated assumptions. The registry's description says the planning illustration uses an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also distinguishes total events for time-to-event outcomes from participants per arm for other outcomes. These are planning assumptions, not evidence that the study had a particular power or that its design used those calculations. The observed effect and calculated sample-size outputs are not reported in the registry record. Any sample-size illustration should therefore be read as hypothetical planning information, not observed power or a trial result.

More generally, power is a design probability under a specified model and assumed effect. It is not a measure of whether a completed study's result is true, and a post hoc power calculation does not substitute for an estimate with its uncertainty. The record does not report a sample-size justification for this dose-finding study. It also does not report the statistical plan in enough detail to identify the planned estimators, confidence-interval methods, or hypothesis tests.

Why do adverse-event counts not replace the endpoint?

In general, safety summaries may classify events by seriousness, severity, or relationship to treatment, and those classifications answer different questions. A serious adverse event is not automatically a DLT: the DLT definition has a specified assessment period and criteria, while the registry presents separate serious adverse-event counts. The record does not give a cross-tabulation showing which serious events also met the DLT definition. Serious-event counts therefore cannot be used as a substitute for the missing primary endpoint result.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 24 outcome measures and 0 analyses. Phase 1 secondary outcomes include objective response rate and several pharmacokinetic measures. The study's stated Phase 2 purpose was to examine preliminary activity in three selected tumor types. Reporting multiple outcomes or disease groups can raise multiplicity concerns: in general, when many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for the number and structure of tests. The registry record does not report a multiplicity adjustment, a hierarchy among outcomes, or a prespecified testing strategy.

The record does not report quantitative results for the primary DLT endpoint, objective response rate, or listed pharmacokinetic measures. It also does not report confidence intervals, p-values, or analysis populations for these results. Without such information, readers cannot assess the estimates' precision or determine how analyses of different outcomes were handled.

Missing-data procedures are not reported in the registry record. The record defines a Dose Determining Set based on treatment received and safety assessment, but does not give its size or explain how incomplete assessments, withdrawal, or other missing observations were handled. The primary endpoint population description ends before all details are available, so further eligibility rules cannot be inferred. The total enrollment of 107 should not be treated as the denominator for every outcome.

Interim analyses, stopping rules, and any adjustments to analyses during the study are not reported in the registry record. The study is described as dose-finding, but that description alone does not establish which decision rules or statistical procedures were used. These omissions limit assessment of the confirmatory status and interpretability of any unreported comparisons.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pyrexia (37.5%), hyponatraemia (25.0%), febrile neutropenia (14.3%), nausea (14.3%), vomiting (14.3%).

The registry posts serious adverse-event counts by Phase 1 dose cohort and for the Phase 2 240 mg/m^2 group. For example, serious adverse events were recorded for 10 of 16 participants in the Phase 1 120 mg/m^2 group and 23 of 42 in the Phase 2 240 mg/m^2 group. Other adverse events were recorded for all participants at risk in each listed group. These counts are descriptive summaries, not controlled comparisons.

The listed serious-event terms include pyrexia, hyponatraemia, febrile neutropenia, nausea, vomiting, and pneumonia. The registry reports the corresponding percentages as 37.5%, 25.0%, 14.3%, 14.3%, 14.3%, and 14.3%. These term percentages should be read as the posted summaries; the record does not provide further detail on event counts by term, overlap among terms, or the calculation denominator for each term.

The registry also gives a death count for each group. It does not report causes of death or a causal attribution, so the counts alone do not indicate whether a death was related to treatment or disease. Serious adverse events are distinct from the primary DLT endpoint, which has its own definition and assessment window. The DLT count is not reported in the registry record. Differences between cohorts should not be read as dose effects because the study was nonrandomized and did not include a control group.

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

The registry record establishes that this was a completed, nonrandomized Phase 1/2 study of nab-paclitaxel in pediatric patients and young adults with recurrent or refractory solid tumors. It describes planned Phase 1 doses, the Phase 2 dose, the primary DLT definition, and selected adverse-event counts. It does not report the primary endpoint result, quantitative tumor-response findings, or pharmacokinetic results.

Accordingly, the posted data do not permit a numerical assessment of how often DLTs occurred, how precisely that frequency was estimated, or how response varied across tumor types. The fact that the record names a recommended Phase 2 dose does not, by itself, reveal the dose-selection evidence or the uncertainty around that decision. Those details are not reported in the registry record.

The safety summaries show that serious adverse events were recorded in each listed group, and the record names several serious-event terms. These observations are descriptive. They do not establish that nab-paclitaxel caused an event, nor do they establish that an event was a DLT. The posted death counts likewise lack reported causes or attribution. No randomized comparator is available to estimate how these outcomes would differ under another treatment or under no study treatment.

In general, a clinical trial result is most informative when the endpoint definition, analysis population, observed estimate, and measure of uncertainty are considered together. Here, important outcome estimates and analysis details are not reported in the registry record. The enrollment figure of 107 is the study-wide total and cannot be assumed to be the number evaluated for every endpoint.

The record therefore supports an account of the study's design and selected safety reporting, but not a conclusion about treatment efficacy, comparative safety, or the size and precision of the primary endpoint result. Those questions require outcome data and analyses that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why dose-finding and efficacy questions need to be kept distinct. Phase 1 focused on identifying a dose using DLT assessment, while Phase 2 was intended to examine preliminary activity in selected tumor types. The dose selected for a later phase is not itself an efficacy result, and a DLT count is not a tumor-response measure.

The study also illustrates the importance of the analysis population. Total enrollment was 107, while the primary endpoint applied to a defined Dose Determining Set with treatment and safety-assessment requirements. Without the size of that set and its DLT count, readers cannot derive or judge the primary endpoint estimate. A study-wide enrollment figure cannot replace endpoint-specific denominators.

Another statistical lesson is that dose cohorts in a nonrandomized study are not control groups. Cohort counts can be useful descriptive information, but they do not provide a randomized comparison. The same caution applies to comparisons between the Phase 1 and Phase 2 populations, which differ in purpose and include distinct tumor groups.

Finally, a registry entry can describe detailed endpoint definitions and safety events while still lacking the estimates needed to assess precision and clinical activity. This record lists the DLT criteria and reports serious adverse-event summaries, yet does not report the DLT result, response results, or statistical analyses. Transparent reporting of denominators, endpoint results, uncertainty, and analysis procedures is essential for readers to understand what the study found and what remains unresolved.

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 main limitation for statistical interpretation is that the registry record does not report the primary DLT count or the number of participants in the Dose Determining Set. Without those values, the primary endpoint cannot be quantified. The record's DDS description is incomplete, so additional details about membership cannot be recovered from the entry.

The record does not report quantitative Phase 2 response results or results for the listed Phase 1 pharmacokinetic outcomes. It lists 24 outcome measures and 0 analyses, but does not provide estimates, confidence intervals, or p-values. The statistical analysis plan, multiplicity approach, missing-data methods, and interim-analysis procedures are not reported in the registry record.

The study was open-label, nonrandomized, and single group. There was no randomized comparator, and the listed dose and disease groups are not like-for-like control arms. As a result, the posted group counts cannot support a causal comparison. The registry does not report whether outcome assessment included independent review or other bias-reduction procedures.

The safety summary supplies counts by group and selected serious-event terms, but does not report causes of death, treatment attribution for deaths, or the overlap between serious adverse events and DLTs. The adverse-event summaries therefore cannot fill the gap in the primary endpoint reporting. The full distribution of participants across diagnoses and the endpoint-specific follow-up are also not reported in the registry record.

These limitations concern what can be concluded from the posted registry information; they do not establish that data or analyses were absent from other study materials. Those materials are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors — NCT01962103.
• Registry record last updated 2019-12-27; status last verified 2019-12.
• Results first posted 2018-12-27.
• 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 a completed, multicenter, open-label, nonrandomized Phase 1/2 study of nab-paclitaxel in 107 pediatric patients and young adults with recurrent or refractory solid tumors. Phase 1 evaluated planned dose cohorts from 120 mg/m^2 to 270 mg/m^2, with DLTs as the primary endpoint. Phase 2 evaluated the RP2D in participants with Ewing's sarcoma, neuroblastoma, or rhabdomyosarcoma.

The entry includes DLT criteria, treatment schedules, selected serious adverse-event counts, and death counts by group. It does not report the primary DLT result, quantitative response or pharmacokinetic results, or statistical analyses. Because the study had no randomized comparator and endpoint-specific population sizes are not reported, the posted information supports a design and safety-reporting description, not a comparative estimate of treatment effect.