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 A Study of Lymphoseek® as a Lymphoid Tissue Targeting Agent in Pediatric Patients With Melanoma, Rhabdomyosarcoma, or Other Solid Tumors Who Are Undergoing Lymph Node Mapping (NCT02509598), a na phase 2 study. The primary outcome is Average Number of Lymph Nodes Identified Intraoperatively Per Subject.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02509598 |
| Phase | Phase 2 |
| Condition | Rhabdomyosarcoma, Melanoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Cardinal Health 414, LLC |
| Results posted | Yes |
2. Clinical Question
Population
Pediatric patients with melanoma, rhabdomyosarcoma, or other solid tumors undergoing lymph node mapping. The brief summary describes eligibility from neonatal age through 17 years.
Intervention
A single administration of Tc99m tilmanocept, identified by the brand name Lymphoseek, for lymph node mapping. Vital Blue Dye could optionally be administered.
Comparator
The study is described as a within-subject comparison, with optional comparison to Vital Blue Dye. It is not a randomized comparison, and the dye was optional rather than a uniformly assigned control.
Primary question
What was the average number of lymph nodes identified intraoperatively per subject after Lymphoseek administration? The registry record specifies this endpoint but does not report its estimate or confidence interval.
The clinical question is about lymph node localization during mapping, not a randomized test of treatment against a parallel control group. The brief summary describes an open-label, non-randomized, multicenter study in pediatric patients with melanoma, rhabdomyosarcoma, or another solid tumor. The intervention description specifies Tc99m tilmanocept, while the optional dye offers a possible within-subject point of comparison where used.
The registry also lists preoperative imaging, localization agreement, upstaging, false-negative rate, sensitivity, and pathology agreement among secondary outcomes. These outcomes address different parts of the mapping and assessment process. They should not be treated as interchangeable measures: identifying nodes, comparing localization methods, and assessing tumor findings in excised nodes answer distinct questions.
The primary endpoint is the average number of nodes identified intraoperatively per subject, with a one-day timeframe recorded. Without the posted mean and its 95% confidence interval, the record does not establish the observed average or its precision. Nor does the endpoint by itself describe how often nodes were positive for tumor, whether mapping changed staging, or how localization compared with the optional dye.
3. Trial Design
This was a prospective, open-label, multicenter, phase 2 study. The registry identifies the design as single-group and non-randomized, with allocation listed as not applicable and no masking. Its brief summary characterizes the study as a within-subject comparison of Lymphoseek, with optional comparison to Vital Blue Dye, in pediatric patients undergoing lymph node mapping.
The registry lists enrollment as 24 and status as completed. The recorded start is 2015-08, and primary completion is dated 2019-03-06. The population included patients with melanoma, rhabdomyosarcoma, or other solid tumors; the brief summary says age could range from neonatal through 17 years. The conditions field names melanoma and rhabdomyosarcoma.
The intervention is Tc99m tilmanocept, also referred to as Lymphoseek. The arm description specifies a single administration of 0.5 mCi and 50 ug. Vital Blue Dye was optional, with a single administration of 1-3 mL per institutional standard of care. Lymph node mapping is also listed as a procedure. Because the dye was optional and there was no randomized allocation, comparisons involving dye use do not constitute a randomized, like-for-like control comparison.
The primary outcome is the average number of lymph nodes identified intraoperatively per subject, reported in nodes per subject, with a 95% confidence interval as the specified dispersion measure and a timeframe of 1 Day. The record lists 12 outcome measures overall, including secondary measures related to preoperative SPECT or SPECT/CT, node localization, upstaging, false-negative rate, sensitivity, and pathology agreement.
The registry record does not report a statistical analysis plan, an analysis population, or outcome estimates. The completed status therefore does not, on its own, supply the missing numerical results or describe which participants contributed to each analysis.
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
| Stage | Tc99m Tilmanocept and Vital Blue Dye (Optional) |
|---|---|
| STARTED | 24 |
| COMPLETED | 23 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Tc99m Tilmanocept and Vital Blue Dye (Optional) |
|---|---|
| Withdrawal by Subject | 1 |
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 | Tc99m Tilmanocept and Vital Blue Dye (Optional) |
|---|---|---|
| Participants analysed | 23 | |
| Age, Continuous | years | 11.6 (SD 4.9) |
| Sex: Female, Male: Female | Participants | 15 |
| Sex: Female, Male: Male | Participants | 8 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 |
| Race (NIH/OMB): White | Participants | 21 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Tumor type: Melanoma | Participants | 5 |
| Tumor type: Rhabdomyosarcoma | Participants | 4 |
| Tumor type: Other solid tumors | Participants | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Average Number of Lymph Nodes Identified Intraoperatively Per Subject, measured over 1 Day.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | nodes per subject |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the average number of lymph nodes identified intraoperatively per subject. It is a continuous measure expressed in nodes per subject. In this setting, it describes the amount of lymph node localization achieved during the operative part of mapping, aggregated across subjects as a mean.
A mean can provide a compact description of the typical number of nodes identified, but it does not show the full distribution. Subjects may have different numbers of localized nodes, and a mean alone does not reveal how variable those numbers were or whether a small number of subjects had unusually high or low values. The specified 95% confidence interval is intended to convey uncertainty around the estimated mean, rather than the range of individual subjects’ node counts.
Counting intraoperatively identified nodes is relevant to a mapping study because it focuses on localization during the procedure. It is not, by itself, a measure of whether the nodes contained tumor, whether all relevant nodes were found, or whether the procedure altered clinical decisions. The registry lists separate secondary outcomes for preoperative imaging, agreement between preoperative and intraoperative localization, upstaging, nodal false-negative rate, nodal sensitivity, and pathology agreement. Those measures address additional diagnostic questions.
The registry record does not report the primary endpoint’s observed mean or confidence interval. It therefore supports describing what was intended to be measured, but not the numerical level of node identification or the precision of that estimate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record defines a specific primary outcome: the average number of lymph nodes identified intraoperatively per subject. It also specifies a 95% confidence interval and a timeframe of 1 Day. However, no numerical result for this endpoint appears in the registry record. The observed mean, its confidence interval, and the number of participants contributing to that endpoint are not reported in the registry record. Consequently, the size and precision of the primary estimate cannot be assessed from this record.
The distinction between an endpoint definition and an outcome result matters. Naming an outcome tells readers what the study intended to measure; it does not reveal what was observed. A confidence interval would normally help assess how compatible the data are with different values for the underlying mean. Without the estimate and interval, no such assessment can be made, and it would be inappropriate to infer either a favorable or unfavorable result.
The study’s design also constrains interpretation. It is a non-randomized, single-group study, described as a within-subject comparison with optional Vital Blue Dye. The optional nature of the dye and the absence of randomized allocation mean that the study is not a like-for-like randomized comparison of Lymphoseek against a control group. Any within-subject comparison would need to be interpreted in light of which patients received dye and how the comparison was analyzed; those details are not reported in the registry record.
The listed secondary outcomes span distinct questions, including whether nodes were identified preoperatively with SPECT or SPECT/CT, how preoperative localization agreed with intraoperative localization, and measures of nodal diagnostic performance and pathology agreement. The registry record lists these outcomes but does not report their estimates. A list of planned measures cannot substitute for their results.
Enrollment is listed as 24, but this does not establish that every enrolled participant contributed data to every endpoint. The registry record does not report endpoint-specific denominators, missing outcome data, or analysis populations. It also does not report the study’s statistical analysis plan. These omissions limit interpretation of both the primary endpoint and any comparisons.
In short, the registry record establishes the study question, design, and specified primary measure, but not the numerical answer. The record cannot support a conclusion about the observed number of intraoperatively identified nodes or the uncertainty around that number.
9. Statistical Methods Explained
The primary outcome is a mean, a summary measure for a continuous variable. In general, a mean is calculated by adding the observed values and dividing by the number of observations. For this study, the recorded unit is nodes per subject, so the intended summary concerns each subject’s number of intraoperatively identified nodes. The registry record does not report the mean or the underlying observations, so no calculation or verification of the estimate is possible from the record.
What does a 95% confidence interval mean?
In general, a confidence interval expresses uncertainty about an estimated quantity. A 95% confidence interval around a mean gives a range of values compatible with the data under the assumptions of the method used. It is not a range expected to contain a specified proportion of individual subjects’ values, and it does not mean there is a 95% probability that the particular interval contains the fixed population mean. The registry specifies a 95% confidence interval for the primary outcome, but does not report its endpoints or the method used to construct it.
Confidence interval width is influenced by the amount and variability of the data, as well as the interval procedure. A narrow interval generally indicates a more precise estimate than a wide interval, while neither width alone nor the interval’s location establishes clinical importance. In this record, the interval is not available, and the endpoint-specific sample size and variability are not reported. Precision therefore cannot be judged.
What does the study design allow?
In general, a single-group study can describe outcomes observed among participants receiving the study intervention. A within-subject comparison can compare measurements or localization approaches in the same participant, which avoids treating those observations as if they came from unrelated groups. However, a within-subject design does not automatically eliminate bias. The comparison depends on the measurement process, timing, availability of both measurements, and analytic choices. The registry describes optional comparison to Vital Blue Dye, but the detailed comparison procedures and statistical methods are not reported in the registry record.
Because Vital Blue Dye was optional, participants may not all have had the same comparison information. Optional use can also make the group with a dye comparison different from those without one. Without details on selection, missing measurements, and analysis, a dye comparison should not be interpreted as if participants were randomly assigned to two comparable treatment groups. The registry explicitly lists allocation as not applicable and the study model as single-group.
How should diagnostic outcomes be distinguished?
The outcome list includes measures about preoperative SPECT or SPECT/CT, preoperative node identification, the average number of preoperatively identified nodes, agreement with intraoperative localization, upstaging, nodal false-negative rate, nodal sensitivity, and central versus local pathology agreement. In general, sensitivity concerns how often a method identifies cases with the target condition, while a false-negative rate concerns cases in which the target condition is present but is not detected. Agreement assesses concordance between assessments or methods; agreement is not necessarily the same as accuracy, because two assessments can agree and both be incorrect.
These metrics can have different denominators and depend on definitions of a positive result, reference standard, and evaluable cases. Their interpretation requires the relevant outcome estimates and analysis details. The registry record lists the outcomes but does not report their results, definitions beyond the listed titles, or endpoint-specific denominators.
What do planning assumptions say?
In general, sample-size planning estimates how much information may be needed to detect a specified effect under stated assumptions. The record’s planning assumptions describe illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe detecting a stated fraction of the observed effect. For time-to-event outcomes, the stated convention is to report the total number of events; for other outcomes, it is to report participants per arm.
These are planning illustrations, not a description of the actual single-group trial allocation, and sample-size illustrations are not observed power. The registry record does not report the trial’s own sample-size justification or statistical design plan. Without the observed effect and the corresponding illustrative values, no further interpretation of those planning assumptions is possible.
What is not reported about the analysis?
The registry record does not report the primary estimate, its confidence interval, or an analysis entry. It also does not report the statistical model, distributional assumptions for the node counts, methods for handling missing observations, or any adjustment for multiple outcomes. General statistical choices such as robust methods or transformations might be relevant for some count data, but there is no basis in the record to say whether any were used. Those possibilities should not be mistaken for methods actually applied in this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 12 outcome measures, including the primary measure and several secondary diagnostic outcomes. When a study assesses multiple outcomes, the chance of at least one apparently unusual result can increase if each is interpreted without regard to the full set of analyses. In general, multiplicity methods can control or describe this issue, but the choice depends on the prespecified questions and analysis plan. The registry record does not report whether multiplicity was addressed, which outcomes were prioritized beyond the named primary endpoint, or whether any adjustment was used.
Missing data also matter because the number and characteristics of participants with an observed result can differ by outcome. The record does not report endpoint-specific denominators, how missing measurements were handled, or whether participants with incomplete imaging or pathology information were included in particular analyses. The enrollment value alone does not show how many observations informed the primary mean or each secondary measure.
The analysis populations are not reported in the registry record. It is therefore not possible to determine whether analyses included all enrolled participants, only those who received the intervention, or a subset with evaluable mapping or pathology data. The record also does not provide a protocol-defined approach to exclusions or deviations.
These gaps do not establish that the trial lacked a prespecified plan or that analyses were conducted improperly. They mean only that the registry record does not contain enough information to evaluate multiplicity control, missing-data handling, or the population used for each analysis.
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 |
|---|---|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | 3 | 23 | 13.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | 0 of 23 |
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 |
|---|---|
| Tc99m Tilmanocept and Vital Blue Dye (Optional) | 5 of 23 |
Most frequent serious adverse event terms
| Event term | Organ system | Tc99m Tilmanocept and Vital Blue Dye (Optional) |
|---|---|---|
| febrile neutropenia | Blood and lymphatic system disorders | 2 of 23 |
| Anaemia | Blood and lymphatic system disorders | 1 of 23 |
| hypokalaemia | Metabolism and nutrition disorders | 1 of 23 |
| acute kidney injury | Renal and urinary disorders | 1 of 23 |
| pyrexia | General disorders | 1 of 23 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tc99m Tilmanocept and Vital Blue Dye (Optional) |
|---|---|---|
| Nausea | Gastrointestinal disorders | 4 of 23 |
| Vomiting | Gastrointestinal disorders | 3 of 23 |
Serious events with the highest arm-level rate: febrile neutropenia (8.7%), anaemia (4.3%), hypokalaemia (4.3%), acute kidney injury (4.3%), pyrexia (4.3%).
The adverse-event record lists one group titled Tc99m Tilmanocept and Vital Blue Dye (Optional). In that group, 23 participants were listed as at risk for serious adverse events, and 3 as affected. For other adverse events, 23 were listed as at risk and 5 as affected. The record lists 0 deaths.
These figures describe the registry’s reported group-level counts. The registry record does not provide event-level timing, duration, severity grading, or a detailed account of how participants with multiple events were counted. The figures should not be read as evidence that the intervention caused the events; the record does not establish causality in the counts alone.
The listed serious-event terms include febrile neutropenia at 8.7%, Anaemia at 4.3%, hypokalaemia at 4.3%, acute kidney injury at 4.3%, and pyrexia at 4.3%. These are registry-listed term percentages. Their precise denominator and whether the figures refer to participants or events are not reported in the registry record, so they should not be converted into counts or compared as if their basis were fully specified.
Safety interpretation is also limited by the lack of a randomized control group. The record’s design is single-group, and Vital Blue Dye was optional. These figures therefore describe reported events in the listed group; they do not provide a controlled estimate of excess risk attributable to Lymphoseek.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a prospective, open-label, multicenter phase 2 study evaluated Lymphoseek as a lymphoid tissue targeting agent in pediatric patients undergoing lymph node mapping. It identifies the primary outcome as the average number of lymph nodes identified intraoperatively per subject and specifies a 95% confidence interval. These details clarify the intended measurement and the type of uncertainty the record planned to report.
The numerical primary result is not reported in the registry record. Without the mean, confidence interval, endpoint denominator, and analysis details, the observed level of intraoperative node identification and its precision cannot be assessed. A completed study status does not fill in those missing data. The record also does not report the listed secondary outcome estimates, so conclusions about preoperative imaging, localization agreement, upstaging, sensitivity, false-negative rates, or pathology agreement are not available from this record.
The design is not a randomized comparison. The study is described as single-group and non-randomized, with an optional within-subject comparison to Vital Blue Dye. Consequently, the record does not establish a controlled contrast between Lymphoseek and a uniformly assigned alternative. Any comparison would depend on the data collected and methods used, which are not reported.
The recorded safety counts indicate that serious and other adverse events were reported in the intervention group, and the record lists no deaths. These descriptive entries do not by themselves establish causation or comparative safety. The record does not provide the detailed safety context needed to assess event timing, attribution, or comparative rates.
The appropriate interpretation is therefore limited: the registry describes the study’s population, design, intervention, endpoints, and some adverse-event counts, but it does not provide the main efficacy-style endpoint result or the analyses needed to quantify diagnostic performance. No conclusion about the direction, magnitude, or clinical importance of the primary outcome can be drawn from the registry record alone.
13. Why This Trial Matters Statistically
This study illustrates why a clearly named endpoint and a reported endpoint estimate are different parts of the evidence record. The primary measure—average intraoperatively identified lymph nodes per subject—has an explicit unit, timeframe, and specified confidence interval. That gives readers a clear description of the intended summary. Yet without the mean and interval, the actual result and its precision remain unavailable.
The design also highlights how comparison structure shapes interpretation. A prospective, open-label, non-randomized, single-group study can characterize observations during mapping and may include within-subject information. But optional use of Vital Blue Dye does not create a randomized control group. Statistical comparisons need to reflect that design rather than imply treatment allocation or balance that the registry does not describe.
The secondary outcomes show that mapping studies can involve several related but distinct diagnostic questions. Node detection, agreement between localization approaches, sensitivity, false-negative rate, and pathology agreement are not interchangeable. Reporting the estimates and their denominators would be necessary to understand each outcome on its own terms and to assess whether findings are consistent across stages of the mapping process.
Finally, the record demonstrates the importance of reporting analysis populations, missing-data handling, and methods for multiple outcomes. Without these details, readers cannot assess how much data informed each result or how uncertainty and multiple testing were addressed. These are general reporting considerations; the registry record does not say whether such methods were used elsewhere. For this study, the registry’s design and endpoint definitions are informative, while the absent outcome estimates limit statistical interpretation.
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.
A central limitation of interpretation is that the registry record does not report the primary endpoint estimate or its 95% confidence interval. It also does not report the number of participants contributing to that endpoint. The recorded enrollment of 24 cannot be treated as the analysis denominator, because endpoint-specific participation is not described.
The study was open-label, non-randomized, and single-group. The registry describes an optional within-subject comparison to Vital Blue Dye, but does not report how many participants received dye, how comparison availability was determined, or how any within-subject contrast was analyzed. There is therefore no basis to interpret the study as a randomized comparison or to quantify a controlled difference.
The age range is described broadly as neonatal through 17 years, and the eligible conditions include melanoma, rhabdomyosarcoma, or other solid tumors. The registry does not report the distribution of participants across ages, diagnoses, or other clinical characteristics. The extent to which results might differ across these groups cannot be assessed from this record, especially because the outcome results themselves are absent.
Although the record lists secondary diagnostic outcomes, it does not report their estimates, denominators, or detailed definitions. Nor does it report missing-data methods, analysis populations, multiplicity handling, or the statistical methods used for the primary mean and confidence interval. These omissions prevent assessment of precision, completeness, and the robustness of any analyses.
The safety entries are also limited: the record gives group-level counts and selected terms, but detailed event descriptions, attribution, and denominator context for the listed percentages are not reported. These limitations concern what can be learned from the registry record; they do not establish that the study lacked further documentation or analyses.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Lymphoseek® as a Lymphoid Tissue Targeting Agent in Pediatric Patients With Melanoma, Rhabdomyosarcoma, or Other Solid Tumors Who Are Undergoing Lymph Node Mapping — NCT02509598.
- Registry record last updated 2024-06-28; status last verified 2024-06.
- Results first posted 2024-06-28.
- 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
NCT02509598 is a completed, prospective, open-label, multicenter phase 2 study of Tc99m tilmanocept, or Lymphoseek, for lymph node mapping in pediatric patients with melanoma, rhabdomyosarcoma, or other solid tumors. The registry describes a non-randomized, single-group, within-subject study with optional Vital Blue Dye comparison. Enrollment is listed as 24.
The primary outcome is the average number of lymph nodes identified intraoperatively per subject, with a 95% confidence interval and a timeframe of 1 Day. The registry record does not report the primary estimate or its interval. It lists 12 outcome measures, but does not report the outcome estimates or analysis details needed to assess them.
The adverse-event record lists 3 serious-event affected participants and 5 affected participants for other adverse events, each among 23 listed at risk, and 0 deaths. The design and optional comparator do not support a randomized control interpretation. Overall, the registry defines the study question and design but does not provide the numerical primary result.