Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer (NCT01502410), a non-randomized phase 2 study. The primary outcome is Objective Response by RECIST Criteria v 1.1.

2. Clinical Question

3. Trial Design

This was a phase II, non-randomized study sponsored by the National Cancer Institute (NCI). The registry lists a single-group model and no masking. It enrolled 20 participants overall and included disease-specific groups for relapsed or refractory rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma, and papillary thyroid carcinoma. The registry record reports no accruals in the hepatocellular carcinoma and thyroid carcinoma groups; the primary analysis population was therefore restricted to rhabdomyosarcoma and Wilms tumor.

Participants received oral sorafenib tosylate twice daily on days 1–28, with courses repeating every 28 days for up to 24 courses unless disease progression or unacceptable toxicity occurred. The primary outcome was objective response by RECIST version 1.1 over 6 cycles (168 days). Secondary outcomes included progression-free survival, grade 3 or higher toxicity, pharmacokinetic parameters, changes in VEGF and VEGFR-2, and the presence of BRAF mutation or RET/PTC rearrangement. The registry lists six secondary outcomes.

The record is marked completed, with a start date of 2012-01 and primary completion in 2014-06. It does not report a randomized comparison, masking, or a control arm. Accordingly, the study design can describe responses and adverse events observed in treated participants, but it does not by itself separate treatment effects from the natural course of disease or other influences. The registry record does not report how participants were assigned among the disease-specific groups or give further operational details about enrollment into each group.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Only Rhabdomyosarcoma and Wilms Tumor patients are included in this analysis as there were no accruals on Hepatocellular carcinoma and no accruals on Thyroid carcinoma.

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 Objective Response by RECIST Criteria v 1.1, measured over 6 cycles (168 days).

The primary endpoint was the number of evaluable participants who were objective responders by RECIST version 1.1 at 6 cycles (168 days). RECIST classifies tumor response from changes in target lesions and the appearance of new lesions. A complete response requires disappearance of all target lesions. A partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions relative to baseline. Stable disease falls short of the shrinkage or increase thresholds for partial response or progressive disease. Progressive disease requires at least a 20% increase relative to the smallest recorded sum after treatment began, or the appearance of one or more new lesions.

Objective response is used to describe measurable tumor change under a defined set of criteria. It provides a categorical outcome—responder or not a responder—rather than a direct measure of how long disease control lasts or how participants feel and function. The registry specifies that response rates are calculated from evaluable participants who are responders. It does not report the number evaluable, the number who responded, or an estimated response rate. The stated primary analysis excludes hepatocellular carcinoma and thyroid carcinoma because there were no accruals in those groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help define what an endpoint means, which participants contribute to it, and how uncertain an estimate may be. For this study, the registry specifies a binary primary outcome: a participant is classified as an objective responder or not, using RECIST version 1.1. It states that the response rate is calculated from evaluable participants who are responders. The registry record does not report a statistical analysis plan, a confidence interval method, a hypothesis test, or the observed response data.

What does a response count represent?

A response count is the number of evaluable participants meeting the response definition. A response rate places that count in relation to the evaluable participants assessed. The denominator matters because enrolled participants may not all be evaluable for the endpoint; the record does not state how many were evaluable or how evaluability was determined. It also does not report how missing or unevaluable response assessments were handled. Without the count and denominator, neither a response rate nor its precision can be established from the registry entry.

RECIST makes the classification more reproducible by defining response categories through lesion measurements and new-lesion status. The stated criteria distinguish disappearance of target lesions, a specified degree of shrinkage, neither sufficient shrinkage nor increase, and a specified increase or new lesions. In general, a threshold-based outcome simplifies complex measurements into categories, but it does not preserve every detail of tumor change. Two participants close to a category boundary may be classified differently even if their underlying measurements are similar.

What does a confidence interval add?

In general, a confidence interval describes the uncertainty around an estimated quantity under a stated statistical method. For a response rate, it would communicate how much precision the observed count and denominator support. It would not correct biases caused by participant selection, missing assessments, or the lack of a comparison group. No confidence interval for the primary outcome is reported in the registry record, so the precision of the response estimate cannot be assessed.

Why does the design matter?

Random allocation is a general method for balancing measured and unmeasured prognostic factors between treatment groups, on average. This study was non-randomized and had no control arm, so it cannot use a randomized comparison to address those sources of imbalance. The groups were organized by cancer type, which also means the observed outcomes in different groups would not automatically be interpretable as treatment contrasts. The study can describe outcomes among treated participants, but the registry record does not support a treatment-versus-control effect estimate.

General comparisons between groups also require care when groups differ in disease, eligibility, or follow-up. The record identifies distinct disease-specific groups, but it does not report detailed baseline characteristics or group-specific primary response results. Therefore, it is not possible to assess comparability or to determine whether apparent differences would reflect treatment response, disease characteristics, or other factors.

How should planning calculations be read?

In general, sample-size planning asks how many participants a future study might need under specified assumptions about an effect, significance level, allocation, and statistical model. The registry’s planning description refers to a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as fractions of an observed effect. It labels those calculations as planning illustrations, not as the trial’s own design. A planning illustration is not an observed result, and it is not observed power. The registry record does not report a sample-size justification for the trial or an analysis plan connecting those planning assumptions to the study’s primary endpoint.

For time-to-event outcomes, general methods can account for the timing of events and censoring; the registry’s planning description says such calculations use a total event count. Other planning calculations are described in terms of participants per arm. These are methodological distinctions, not results from the trial. The record does not report the values needed to reproduce a calculation, and no new estimates can be inferred from the design information alone.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability exceeds what a statistical model assumes. If ignored, uncertainty estimates can be too small and statistical evidence can appear stronger than it is. Whether over-dispersion is relevant depends on the outcome and model. The registry does not report a model for the primary binary endpoint or any assessment of over-dispersion, so it is not possible to say that this issue was evaluated in this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six secondary outcomes, alongside the primary objective-response endpoint. When a study examines multiple outcomes or performs multiple statistical tests, the chance of at least one apparently notable finding can increase. General approaches include designating a primary endpoint in advance, adjusting significance thresholds, or treating secondary findings as exploratory. The registry record does not report whether multiplicity adjustments were planned or used, nor does it describe a hierarchy among secondary outcomes. It therefore does not support a claim that reported findings were adjusted for multiple testing.

The primary response definition refers to evaluable participants, but the number evaluable and the handling of missing assessments are not reported in the registry record. No imputation method, sensitivity analysis, or rule for classifying participants without an assessment is reported. This matters because the response estimate depends on who is included in its denominator and on how unavailable outcome measurements are treated.

The record identifies the primary analysis population as rhabdomyosarcoma and Wilms tumor participants, excluding the cancer groups with no accruals. It does not report further analysis-population definitions, such as whether all enrolled participants or only participants meeting specific assessment conditions were included in other analyses. No analysis results are listed in the registry record. The statistical analysis plan, including any interim analyses, is not reported in the registry record.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pain (20.0%), anorexia (10.0%), back pain (10.0%), fatigue (10.0%), musculoskeletal and connective tissue disorder - other (10.0%).

The registry reports serious and other adverse-event summaries separately for the rhabdomyosarcoma and Wilms tumor groups. For rhabdomyosarcoma, 10 participants were listed as at risk for serious adverse events and 4 as affected; for other adverse events, 10 were listed as at risk and 5 as affected. For Wilms tumor, 10 were listed as at risk for serious adverse events and 3 as affected; for other adverse events, 10 were listed as at risk and 6 as affected. These are descriptive counts, not a randomized comparison.

The listed serious-event terms include Pain at 20.0%, and Anorexia, Back pain, Fatigue, Musculoskeletal and connective tissue disorder - Other, and Neck pain at 10.0% each. The registry record does not state the denominators for those term percentages in the term list. The serious-event summaries should not be conflated with the separate secondary outcome of grade 3 or higher toxicity, whose result is not reported in the registry record. Death counts are not reported in the registry record. These summaries do not establish causation or provide full information about event timing, duration, or recurrence.

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

The study record establishes that sorafenib tosylate was investigated in children and young adults with several relapsed or refractory cancers, using a phase II, non-randomized design. Its primary endpoint was objective response by RECIST version 1.1 over 6 cycles (168 days), with the primary analysis restricted to rhabdomyosarcoma and Wilms tumor. The registry provides the outcome definition and selected safety counts, but it does not report the primary response result.

That missing result means the response frequency and its precision cannot be described from this record. It does not mean that no participants responded, and it does not show that the treatment failed or succeeded. No response count, denominator, rate, or uncertainty interval is reported. The secondary outcome results are also not reported in the registry record, including progression-free survival and grade 3 or higher toxicity.

The design further limits what can be concluded. Since there was no randomized control group, observed outcomes among treated participants cannot establish what would have happened under a different treatment or without study treatment. The absence of accruals in the liver and thyroid cancer groups also means that the primary analysis does not answer the response question for those diagnoses. The posted safety counts are useful descriptions, but they are not evidence of a comparative safety difference.

In short, the record documents the trial question, treatment schedule, response criteria, and some adverse-event summaries. It does not report enough outcome information to estimate the primary response result or support a causal comparison. Interpretation should remain within those boundaries.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint is not the same as a reported result. RECIST version 1.1 specifies how tumor measurements translate into response categories, and the registry states the assessment period and the population intended for the primary analysis. Those details make the question interpretable. But without the number evaluable and the number responding, the endpoint cannot be quantified from the record.

It also shows why analysis populations and disease groups need to be explicit. Although the study included four cancer groups, the registry states that the primary analysis includes only rhabdomyosarcoma and Wilms tumor because there were no accruals in the hepatocellular carcinoma and thyroid carcinoma groups. The overall enrollment figure is therefore not the primary endpoint denominator. Clear population definitions help prevent a study-wide enrollment count from being mistaken for the number contributing to an outcome.

The non-randomized, single-group model is another important statistical feature. Descriptive response and safety findings can be useful for characterizing participants who received study treatment, but they cannot provide a controlled treatment contrast. The registry’s selected adverse-event counts likewise require attention to outcome definitions and denominators: serious adverse events, other adverse events, and grade 3 or higher toxicity are not interchangeable measures.

Finally, the record highlights the difference between planning and evidence. Sample-size illustrations depend on assumptions and do not substitute for observed outcomes or establish observed power. For clinical researchers and biostatisticians, the key lesson is to distinguish design information, endpoint definitions, and descriptive safety summaries from the actual results needed to estimate response and uncertainty.

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 limitation for interpreting efficacy is that the response result is not reported in the registry record. The number evaluable, the responder count, and any estimate of uncertainty are also not reported. The stated primary population excludes hepatocellular carcinoma and thyroid carcinoma because there were no accruals in those groups, so the primary endpoint cannot describe those diagnoses.

The study was non-randomized, had no masking, and is listed as a single-group model. No concurrent control group is described. This limits causal interpretation and prevents a randomized estimate of a treatment contrast. The record does not report detailed baseline characteristics, group-specific primary outcome results, or information sufficient to assess comparability among disease groups.

Important analysis details are not reported in the registry record, including the statistical analysis plan, missing-data handling, multiplicity procedures, and any interim analyses. The primary endpoint depends on evaluability, but the rules used to determine evaluability are not stated. The record also does not report the results for the listed secondary outcomes. Safety summaries do not include reported death counts, and the denominators for the listed serious-event term percentages are not stated with those terms. These limitations restrict both the precision and scope of conclusions that can be drawn from the registry entry.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Sorafenib Tosylate in Treating Younger Patients With Relapsed or Refractory Rhabdomyosarcoma, Wilms Tumor, Liver Cancer, or Thyroid Cancer — NCT01502410.
• Registry record last updated 2018-06-26; status last verified 2018-06.
• Results first posted 2015-05-15.
• 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

This completed phase II study evaluated sorafenib tosylate in children and young adults with relapsed or refractory rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma, or papillary thyroid carcinoma. It was non-randomized, unmasked, and listed as a single-group model, with 20 participants enrolled overall. The primary endpoint was objective response by RECIST version 1.1 over 6 cycles (168 days), with the primary analysis limited to rhabdomyosarcoma and Wilms tumor because there were no accruals in the other two cancer groups. The registry record does not report the primary response result or secondary outcome results. It reports selected adverse-event counts by group, but those summaries do not support a controlled safety comparison.