Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors (NCT02867592), a na phase 2 study. The primary outcome is Objective Response (Non-Osteosarcoma Strata).

2. Clinical Question

The clinical question is not a randomized comparison of cabozantinib-s-malate with another treatment or with a control condition. Instead, the primary outcome is a response proportion within the trial’s eligible non-osteosarcoma population. The registry names Ewing’s Sarcoma, Rhabdomyosarcoma, Non-Rhabdomyosarcoma Soft Tissue Sarcoma, and Rare Tumors as statistical strata, as well as strata that accrued enough patients to be an additional stratum. The final phrase describing that additional eligibility criterion is incomplete in the registry record, so its full definition is not reported there.

The study also includes an osteosarcoma group, but osteosarcoma is excluded from the stated primary response endpoint. The registry lists adverse events, pharmacokinetic measures, time to progression, and progression-free survival among secondary outcomes. Those outcomes address other aspects of treatment experience and disease course; they do not replace the primary response question.

3. Trial Design

This is a phase 2, single-group study sponsored by the National Cancer Institute (NCI). The registry records enrollment of 109 and allocation as not applicable. Masking is listed as none. These design features mean the record does not describe random assignment to treatment groups or a blinded comparison. The study is titled for younger patients with recurrent, refractory, or newly diagnosed sarcomas, Wilms tumor, and other rare tumors, and its condition list includes a broad range of tumor types and disease states.

Patients receive cabozantinib-s-malate orally on a continuous dosing schedule, with dosing guided by a nomogram on days 1-28. Treatment cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. The registry lists cabozantinib and cabozantinib s-malate as drug interventions, alongside a pharmacological study. It does not describe a parallel control arm.

The primary outcome is objective response in non-osteosarcoma strata, measured through the first 6 cycles of therapy. Response is defined as complete response or partial response under RECIST version 1.1. The registry says response rates are calculated among evaluable patients and that confidence intervals account for a two-stage design. The operational details of the two-stage design and the evaluability criteria are not fully reported in the registry record.

The record gives a study start date of 2017-05-18 and a primary completion date of 2021-06-30, while listing the study status as active, not recruiting. The record does not report a separate trial phase beyond phase 2, or the rationale used to select the planned enrollment. Enrollment describes the recorded study total, not the size of the primary endpoint population, which is defined by evaluability and stratum.

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: All patients who met the evaluable for response criteria outlined in section 9.4 of the ADVL1622 protocol in non-osteosarcoma strata which were either statistical strata (Ewing's Sarcoma, Rhabdomyosarcoma, Non-Rhabdomyosarcoma Soft Tissue Sarcoma, and Rare Tumors) or accrued enough patients to be analyzed (Wilms Tumor). Data is limited for Rare tumors due to low accrual.

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 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response (Non-Osteosarcoma Strata), measured over Up to the first 6 cycles of therapy.

The primary endpoint is the percentage of evaluable patients in the specified non-osteosarcoma strata whose best overall response is complete response or partial response. Response is assessed using Response Evaluation Criteria in Solid Tumors version 1.1, and the assessment period extends through the first 6 cycles of therapy. The endpoint therefore summarizes whether a patient met a prespecified tumor-response category during that period; it is not a measure of how long response lasts.

A response proportion is useful in a phase 2 study because it gives a direct description of the share of evaluable participants who meet the stated response definition. Its interpretation depends on the denominator: participants who are not evaluable are not included in the stated calculation, so the response percentage does not automatically describe every enrolled participant. The registry record does not provide the number evaluable for the primary endpoint or the resulting response percentage.

The registry specifies a 95% confidence interval and says its construction accounts for the two-stage design. A confidence interval communicates uncertainty around the estimated response proportion. Its width depends on the information available and on the method used. The record does not give the interval limits or the response estimate, so the precision of the observed primary result cannot be assessed from the registry information. Response is only one dimension of outcomes; it does not by itself summarize adverse events, pharmacokinetics, progression, or survival.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary response indicator at the participant level: a patient is counted as a responder if the best overall response is partial response or complete response. The registry states that response is assessed by RECIST version 1.1. The percentage is calculated among patients who meet the protocol’s response-evaluable criteria, within the specified non-osteosarcoma strata. The registry does not report the resulting numerator or denominator.

What does a response percentage describe?

In general, a response percentage is an estimated proportion in a defined analysis population. Its meaning depends on who is included, what counts as a response, and the period during which response is assessed. In this trial, the stated period is up to the first 6 cycles of therapy. The outcome is not a count of every tumor change, nor does it describe response duration. Because the analysis is restricted to evaluable patients, interpretation also depends on how evaluability was defined and what happened to participants without sufficient assessments. The registry refers to criteria in section 9.4 of the ADVL1622 protocol but does not reproduce those criteria in full.

How should the confidence interval be understood?

In general, a confidence interval gives a range of values compatible with the observed estimate under the chosen statistical method. It represents uncertainty in an estimate, rather than a range containing a fixed percentage of individual patient outcomes. A narrower interval indicates greater precision under that method, while a wider interval indicates less precision. The registry specifies a 95% confidence interval for the response rate and states that its construction accounts for the two-stage design. Neither the estimate nor the interval limits are reported, so the actual precision cannot be evaluated.

Why does the two-stage design matter?

In general, a two-stage design allows a study to assess accumulating outcome information in stages. The design can include a planned rule for whether study activity should continue after an earlier stage, but the specific rules and decision thresholds cannot be inferred from the phrase alone. The registry says the confidence interval will account for the two-stage design. The stage-specific enrollment targets, stopping rules, and any interim decision procedures are not reported in the registry record. It would therefore be inappropriate to infer how the design operated or what decisions were made.

What can a single-group design estimate?

In general, a single-group study can describe outcomes observed among participants who received the intervention, subject to the defined analysis population and follow-up. It does not provide a concurrent randomized control group for estimating a between-group treatment contrast. In this trial, allocation is recorded as not applicable and masking as none. Those features do not invalidate a response proportion as a descriptive endpoint, but they constrain causal interpretation. The response percentage, if reported, would be an outcome in the studied participants, not a randomized comparison.

How do secondary outcomes differ?

The registry lists adverse events, pharmacokinetic measures including Cmax, Tmax, AUC, accumulation, and half-life, and time-to-event outcomes including time to progression and progression-free survival. These outcomes answer different questions. Pharmacokinetic measures describe drug exposure or its timing; event and progression outcomes describe safety or disease course. Their definitions and analysis details are not fully available in the registry information. A result on one outcome cannot be treated as a substitute for a result on another.

What does a planning illustration mean?

In general, sample-size planning calculations explore the number of participants needed under specified assumptions about the effect to detect, statistical significance level, allocation, and statistical approximation. The record’s planning description uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, and defines the target effect as a stated fraction of the observed effect. For time-to-event outcomes, the described planning quantity is a total number of events; for other outcomes it is participants per arm. These are planning concepts, not observed trial outcomes or observed power. They also do not establish the actual design justification for this single-group trial. The trial’s own sample-size justification is not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Ewing's Sarcoma", "Rhabdomyosarcoma", "Non-Rhabdomyosarcoma Soft Tissue Sarcoma", "Wilms Tumor", "Rare Tumors")
n      <- c(13, 13, 13, 13, 23)
events <- c(0, 0, 0, 0, 3)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Ewing's Sarcoma  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2
ARM  Rhabdomyosarcoma  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2
ARM  Non-Rhabdomyosarcoma Soft Tissue Sarcoma  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2
ARM  Wilms Tumor  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2
ARM  Rare Tumors  23  3  13.0  2.8  33.6  4.5  32.1  4.7  32.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures and zero analyses. That count does not, by itself, describe how many statistical tests were performed, which outcomes were formally tested, or whether any adjustment for multiple comparisons was planned. The analysis hierarchy, if any, and procedures for handling multiplicity are not reported in the registry record. The primary endpoint is identified, but details about testing or decision rules beyond the statement that the confidence interval accounts for the two-stage design are not given.

Missing outcome data are an important consideration because the primary response percentage is defined among evaluable patients rather than all enrolled participants. The registry refers to protocol criteria for evaluability, but does not provide the complete criteria or the number who met them. It does not describe the amount or pattern of missing response assessments, how unevaluable patients were treated in the analysis, or whether sensitivity analyses were planned. Those details are needed to assess how the analyzed group relates to enrollment.

The stated endpoint population comprises patients who met response-evaluable criteria in selected non-osteosarcoma strata. The record names Ewing’s Sarcoma, Rhabdomyosarcoma, Non-Rhabdomyosarcoma Soft Tissue Sarcoma, and Rare Tumors as statistical strata, and refers to other strata that accrued enough patients to be an additional stratum. The full criterion is not present in the registry record. The primary endpoint result, analysis denominator, and stratum-specific estimates are also not reported.

Accordingly, the registry description does not support a complete assessment of multiplicity, missing-data handling, or analysis-population selection. These are not minor technical details: they help determine which patients contribute to an estimate and how uncertainty and selective reporting should be understood. No assumptions about the unreported procedures should be substituted for the protocol or a full statistical analysis plan.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypoxia (23.1%), infections and infestations - other, specify (15.4%), pericardial effusion (15.4%), disease progression (15.4%), aspartate aminotransferase increased (13.0%).

The registry lists serious adverse events and other adverse events by disease group, with counts for participants at risk and affected, plus a death count. These are group-level safety summaries. For example, the Ewing’s Sarcoma group lists 13 at risk for serious adverse events and 6 affected; its other-adverse-event figures are 13 at risk and 5 affected, with 12 deaths listed. The other groups have their own denominators and counts, so the figures should be read within each named group rather than combined into a single rate.

Among the listed serious-event terms, Hypoxia is reported as 23.1%; Infections and infestations - Other, specify and Pericardial effusion are each 15.4%; Disease progression is 15.4%; Aspartate aminotransferase increased is 13.0%; and Abdominal pain is 8.7%. These percentages do not show whether an event was caused by treatment. The registry information does not give a causal attribution or explain the calculation denominator for each term in the list.

The death counts are listed separately from the affected counts. The record does not establish from these figures alone the cause, timing, or relationship of deaths to treatment. Because this is a single-group study, the adverse-event summaries are descriptive and do not provide a randomized comparison of safety between treatments.

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

The registry record establishes that the study was designed to evaluate cabozantinib-s-malate in younger patients with a range of sarcomas, Wilms tumor, and other rare tumors. It identifies objective response in selected non-osteosarcoma strata as the primary endpoint and specifies the response definition, assessment period, and planned use of a confidence interval accounting for a two-stage design. These details clarify the intended question and the population to which the primary estimate would apply.

The record does not report the primary response percentage, its confidence interval, or the number of evaluable participants. It therefore does not establish the observed size or precision of the response result. A trial’s planned endpoint is not itself evidence that a particular outcome occurred, and no treatment conclusion should be drawn from the endpoint description alone.

Even with a reported response result, a single-group design would describe outcomes in the treated study population rather than estimate a randomized difference against a comparator. The enrollment total of 109 is not necessarily the denominator for the primary endpoint because the stated analysis is limited to evaluable patients within specified strata. The registry does not report how many patients were evaluable or how unevaluable and missing assessments were handled.

The outcome also has a defined scope. It concerns the best overall tumor response during up to the first 6 cycles, not response duration, long-term disease control, or a comparison of harms and benefits. The registry lists other outcomes, including adverse events, pharmacokinetics, time to progression, and progression-free survival, but their inclusion as planned measures is not equivalent to reporting their results. Safety counts and event percentages should likewise be interpreted as descriptive summaries, without assuming that events were attributable to treatment.

Thus, the record supports a careful account of trial design and measurement, but the information available does not permit conclusions about the observed primary response. The distinction between what was planned and what was reported is essential when interpreting a registry entry.

14. Why This Trial Matters Statistically

This study illustrates several statistical issues that are especially relevant when a clinical trial spans uncommon tumor types. The registry includes multiple disease groups, while the primary response question applies to evaluable participants in selected non-osteosarcoma strata. That makes the analysis population central: the overall enrollment figure and the response denominator are not interchangeable. Stratification can help define clinically distinct groups, but the registry’s incomplete description of which additional strata qualified for the primary analysis limits reconstruction of the target population.

The stated two-stage design also matters for interpreting uncertainty. A confidence interval that accounts for a design feature may differ from an interval calculated as though the study were a simple, single-stage sample. The registry acknowledges this in its endpoint description, but does not report the design details or the interval result. This is a reminder that an estimate cannot be assessed fully without both the numerical result and the method used to produce its uncertainty interval.

The single-group structure raises another important distinction: estimating a response proportion is not the same as estimating a treatment effect relative to a control. A well-defined descriptive endpoint can be informative, but it does not provide the randomized contrast that would separate treatment-associated outcomes from outcomes that might otherwise occur. The design and the endpoint must be considered together when interpreting evidence.

Finally, registry records distinguish plans from results. Naming a primary outcome and secondary outcomes does not provide their estimates, and an enrollment total does not establish the final analysis size. This record makes the intended response measure clear, while leaving the observed response estimate and several analysis details unreported. That separation is useful for statistical reading because it prevents design descriptions from being mistaken for outcome evidence.

15. 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 the outcome is that the registry record does not report the objective-response result, the confidence interval, or the number of evaluable patients. Without those items, the magnitude and precision of the primary endpoint cannot be assessed. The overall enrollment of 109 does not resolve this gap because the endpoint applies to a narrower response-evaluable population in selected strata.

The analysis population is not fully reconstructable from the registry description. The record refers to protocol-defined evaluability criteria and names several non-osteosarcoma strata, but the protocol criteria are not reproduced in full. The description of which other strata accrued enough patients to qualify is also incomplete. The number of patients per response stratum, their outcomes, and the handling of unevaluable participants are not reported in the registry record.

The design is single-group, with allocation listed as not applicable and masking as none. As a result, the described study does not offer a randomized comparator for interpreting response or adverse-event differences. The two-stage design is mentioned in the confidence-interval description, but its stage rules, thresholds, and operational details are not reported. The statistical analysis plan, multiplicity procedures, and missing-data methods are likewise not reported in the registry record.

The safety summaries are presented across different disease groups and do not establish event causality. The record does not state in these figures the reasons for deaths or their relationship to treatment. Secondary outcomes are listed, but their results and detailed analysis methods are not included in the information summarized. These limitations mean the registry description can guide interpretation of what was intended to be measured, but it cannot substitute for complete outcome reporting and analysis documentation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors — NCT02867592.
• Registry record last updated 2026-08-28; status last verified 2026-06.
• Results first posted 2022-11-28.
• 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.

19. Record Summary

NCT02867592 is a phase 2, single-group trial sponsored by the National Cancer Institute (NCI), with enrollment recorded as 109. It studies oral cabozantinib-s-malate in children and young adults with sarcomas, Wilms tumor, or other rare tumors. The registry lists no masking and no separate comparator group.

The primary outcome is objective response in evaluable patients in specified non-osteosarcoma strata, assessed by RECIST version 1.1 through the first 6 cycles. The response definition includes complete or partial response, and the registry states that the 95% confidence interval accounts for a two-stage design. The primary response estimate and interval are not reported in the registry record.

Secondary outcomes include adverse events, pharmacokinetic measures, time to progression, and progression-free survival. The record lists the study as active, not recruiting, with a start date of 2017-05-18 and a primary completion date of 2021-06-30.