Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma (NCT04200443), a na phase 2 study. The primary outcome is Progression-free Survival (PFS).

2. Clinical Question

The study concerns people whose leiomyosarcoma or other soft tissue sarcoma cannot be removed surgically or has spread. It is a phase II investigation of two drugs used together. The registry describes cabozantinib as investigational for the indication under study. Its summary gives biological rationales for the drugs, but those rationales are not evidence of a clinical effect in the participants enrolled in this study.

The primary question is framed around progression-free survival (PFS), a measure that captures whether and when disease progression or another specified event occurs. The record sets the primary assessment timeframe as after the first 12 weeks of therapy. It also lists secondary outcomes including presence of response, clinical benefit rate, median progression-free survival, overall survival, adverse events, and participant-reported outcomes. The record does not give results for these outcomes in the posted material.

Because there is no control group, the study can describe outcomes among people who received the combination, but it cannot by itself establish how those outcomes compare with another treatment or with what would have happened without the combination. Interpretation therefore depends on the actual outcome estimates, their precision, follow-up, and the study methods—details that are not reported in the registry record for the primary endpoint.

3. Trial Design

This is a phase II, single-group study sponsored by City of Hope Medical Center. Its allocation is listed as not applicable, and masking is listed as none. The registry record lists planned enrollment of 96. The study began on 2020-01-22, has a primary completion date of 2025-04-04, and is listed as active, not recruiting.

The treatment group receives cabozantinib and temozolomide. The regimen description specifies cabozantinib by mouth once daily on days 1-28 and temozolomide by mouth once daily on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. The listed interventions also include quality-of-life assessment and questionnaire administration.

The registry record describes two disease cohorts: patients with unresectable or metastatic uterine and non-uterine leiomyosarcoma, and patients with other soft tissue sarcomas. The adverse-event summaries list 42 participants at risk in the first cohort and 30 in the second. Those figures are cohort-specific safety denominators; the record does not explain how they relate to the planned enrollment of 96 or to the analysis population for the primary endpoint.

The primary endpoint is PFS, with progression evaluated using RECIST v1.1. The record defines progression for target lesions as at least a 20% increase in the sum of the longest diameter or the appearance of one or more new lesions. For non-target lesions, progression is defined as one or more new lesions and/or unequivocal progression of existing non-target lesions. PFS begins at treatment start and ends at progression, unequivocal clinical deterioration, or death from any cause.

No control arm is described, so differences between the two disease cohorts would not represent a randomized treatment comparison. The protocol’s sample-size justification, detailed statistical plan, interim-analysis plan, and rules for analysis populations are not reported in the registry record. Outcome estimates for the primary endpoint are also 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.

Overall Study

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 Progression-free Survival (PFS), measured over After the first 12 weeks of therapy.

The primary endpoint is progression-free survival (PFS). It measures the time from the start of treatment until the first specified event: disease progression, unequivocal clinical deterioration, or death from any cause. The registry record describes a primary timeframe after the first 12 weeks of therapy and says that the proportion of patients who had a PFS event was calculated.

Progression is assessed using RECIST v1.1. The criteria distinguish target lesions from non-target lesions. For target lesions, the record defines progression as at least a 20% increase in the sum of the longest diameter or the appearance of one or more new lesions. For non-target lesions, progression includes new lesions and/or unequivocal progression of existing non-target lesions.

PFS is used in clinical trials because it captures disease progression as well as death, rather than describing tumor response alone. It is a time-to-event concept: both whether an event occurs and when it occurs can matter. A reported proportion with an event at a specified assessment point is one way of describing the outcome, but it does not by itself provide the full time-to-event distribution or explain how participants without an observed event were handled.

The registry record does not report the primary endpoint estimate, event count, confidence interval, censoring approach, or analysis population. Consequently, the posted information does not establish the observed PFS outcome or its statistical precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas are relevant to reading this study, but the registry record does not describe a complete statistical analysis plan or report the primary endpoint estimate. General explanations below clarify what such methods mean; they do not imply that a particular unreported method was used.

What does a single-group design estimate?

In a single-group study, outcomes are observed among participants who receive the study regimen. The results can describe the frequency and timing of events in that group, subject to the study’s eligibility criteria, follow-up, and data collection. Without a concurrent control group, the study does not directly estimate a randomized contrast between treatments. Differences from an external benchmark, if considered, can be affected by differences in participant selection, disease characteristics, assessment practices, and follow-up. The registry record does not report a comparator or a prespecified external benchmark.

What does a time-to-event endpoint represent?

PFS is a time-to-event outcome: each participant is followed from treatment start until progression, clinical deterioration, or death, as defined in the record. In general, time-to-event analysis can use information from participants whose event has not been observed by the end of their available follow-up. Such observations are often described as censored, meaning that the event time is not known beyond the last point at which the participant was observed. The way censoring is handled and the methods used to estimate PFS are not reported in the registry record.

The record also says the proportion of patients who had a PFS event was calculated, with a timeframe after the first 12 weeks of therapy. A proportion at a specified point summarizes whether an event was observed by that point, but it does not convey all information about the timing of events. The registry record does not state the exact analysis time point, provide a PFS estimate, or clarify whether the reported proportion includes all enrolled participants or another analysis set.

Why does the progression definition matter?

Endpoint definitions determine which observations count as events. Here, progression is evaluated with RECIST v1.1 and has separate definitions for target and non-target lesions. Combining progression, unequivocal clinical deterioration, and death into PFS gives the endpoint broader event coverage than a measure based only on tumor shrinkage. Consistent assessment rules are important because subjective or inconsistent event classification can affect both event counts and timing. The registry record gives the stated criteria but does not report details such as assessment schedules, independent review, or adjudication procedures.

How should uncertainty be assessed?

A confidence interval is a statistical range expressing uncertainty around an estimate under the assumptions of the analysis. A narrow interval generally indicates greater precision than a wide interval, while an interval does not remove design limitations or establish causation. The registry record does not report a confidence interval or other uncertainty measure for the primary endpoint. Therefore, precision cannot be judged from the endpoint definition or planned enrollment alone.

Planned enrollment describes a target, not the number of participants with complete endpoint data or the number of observed events. The record’s planned enrollment is 96, but the primary analysis denominator and event count are not reported in the registry record. A sample-size justification based on a target effect, expected event rate, or desired precision is also not reported in the registry record.

What do counts and percentages convey?

For binary outcomes, a count records how many participants experienced an event, while a proportion relates that count to a stated denominator. Both are needed to interpret frequency. Percentages can look more informative than counts when denominators are unclear, and comparisons across groups are especially difficult when the groups are not randomized or when follow-up differs. The safety summaries give at-risk denominators and counts of participants affected for broad adverse-event categories, but the registry record does not supply detailed participant-level timing or exposure-adjusted rates.

Over-dispersion is a general issue for count outcomes. It occurs when observed variability is greater than expected under a simple count model, potentially because participants differ in their event risk or because events cluster. If present, an analysis that assumes less variability than the data contain can understate uncertainty. The registry record does not report an over-dispersion assessment or a count model for the primary endpoint; the endpoint description instead identifies a proportion of participants with a PFS event.

What do sample-size illustrations mean?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, the significance level, allocation, and analysis method. A calculation based on an observed effect is an illustration, not evidence that a trial was originally designed around that effect. It is also not observed power. The registry record does not report the trial’s own sample-size justification, target effect, or power calculation. No sample-size illustration can substitute for the actual endpoint estimate and its uncertainty.

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("Cohort 1 - Patients With Unresectable or Metastati", "Cohort 2 - Patients With Other Soft Tissue Sarcoma")
n      <- c(42, 30)
events <- c(33, 29)
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  Cohort 1 - Patients With Unresectable or Metastati  42  33  78.6  63.2  89.7  64.1  88.3  64.0  88.2
ARM  Cohort 2 - Patients With Other Soft Tissue Sarcoma  30  29  96.7  82.8  99.9  83.3  99.4  83.3  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and several secondary outcomes: presence of response, clinical benefit rate, median PFS, overall survival, number of participants with adverse events, and participant-reported outcomes. When a study assesses multiple outcomes, the chance of at least one apparently unusual result can increase if each is tested separately without accounting for multiplicity. General approaches include defining a hierarchy of hypotheses or adjusting inference across selected tests. The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or which outcomes were intended for formal hypothesis testing.

The record does not report how missing outcome data were handled. For PFS, a participant may have no recorded event by the end of available follow-up, but the analysis needs explicit rules for follow-up and censoring. The registry record does not describe censoring rules, missed assessments, withdrawal handling, or sensitivity analyses for missing data. These details matter because incomplete follow-up can affect both the event count and the estimated timing of events.

The analysis populations are not reported in the registry record. It is therefore unclear from the posted information which participants would be included in the primary analysis, how treatment discontinuation would be handled, or whether eligibility violations would affect inclusion. The planned enrollment of 96 does not establish the number analyzed for PFS. The at-risk denominators in the adverse-event summaries are safety figures and do not identify the primary endpoint population.

Without a reported statistical plan, analysis population, missing-data approach, and multiplicity strategy, readers cannot fully assess how the outcomes were selected and analyzed. These omissions do not establish that a particular method was or was not used; they mean that the details are not reported in the registry record.

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: dyspnea (6.7%), disease progression (4.8%), myocardial infarction (3.3%), abdominal pain (3.3%), diarrhea (3.3%).

The registry record presents safety information for two disease cohorts. In the cohort with unresectable or metastatic uterine and non-uterine leiomyosarcoma, 42 participants were at risk; 9 were affected by serious adverse events, and 42 were affected by other reported adverse events. In the cohort with other soft tissue sarcomas, 30 participants were at risk; 11 were affected by serious adverse events, and 29 were affected by other reported adverse events.

The record lists deaths for both cohorts: 25 in the leiomyosarcoma cohort and 26 in the other soft tissue sarcoma cohort. These are registry-record counts, not an estimate of deaths caused by treatment. The record does not provide causal attribution for the deaths or the adverse-event counts, nor does it give individual event timelines in this summary.

Several serious-event terms are listed with percentages: dyspnea, 6.7%; disease progression, 4.8%; myocardial infarction, 3.3%; abdominal pain, 3.3%; diarrhea, 3.3%; and death NOS, 3.3%. These entries describe reported terms and percentages; they should not be read as proof that the study regimen caused the events. The record does not provide the term-specific participant counts alongside these percentages in the posted summary.

Safety counts do not alone establish comparative risk. There is no control group, and the record does not report exposure-adjusted rates or detailed follow-up for these summaries. Differences between the cohort figures should not be treated as treatment comparisons.

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

The registry record establishes that this phase II study evaluates cabozantinib with temozolomide in people with unresectable or metastatic leiomyosarcoma or other soft tissue sarcomas. It describes the regimen, the PFS endpoint, the progression criteria, two disease cohorts, and selected safety counts. It does not report the primary PFS result, so the posted information cannot show the observed proportion with a PFS event or the precision of that estimate.

The single-group design can describe what happened among participants who received the combination, once outcome results are reported. It cannot by itself determine how outcomes compare with another treatment. The two disease cohorts are defined by diagnosis, not by randomized assignment, and are not interchangeable control groups.

The registry’s biological explanation for the drugs is background rationale, not a statistical result. Likewise, planned enrollment is not an efficacy outcome, and the listed secondary outcomes do not establish that any particular effect was observed. Safety counts describe events recorded for the cohorts, but without causal attribution they should not be interpreted as treatment-caused events.

General statistical interpretation would require outcome estimates, denominators, uncertainty intervals, follow-up information, and the analysis methods. For PFS, readers would also need the handling of participants without an observed event and the analysis time point. Those details are not reported in the registry record. The record therefore supports a description of design and selected event counts, but not a conclusion about the magnitude or comparative effect of the regimen.

Nothing in a single-group study alone establishes that an outcome would differ under another treatment or under no treatment. The results, when available, would need to be interpreted alongside the study’s eligibility criteria, endpoint assessments, follow-up, and analysis methods. The posted information does not support medical advice or a treatment recommendation.

14. Why This Trial Matters Statistically

This study is statistically notable because it uses a time-to-event primary concept in a single-group phase II design. PFS includes disease progression, unequivocal clinical deterioration, or death, and the registry specifies RECIST v1.1 criteria for progression. That combination makes the event definition central to interpretation: readers need to know not only whether events were counted but also how they were assessed over time.

The study also separates participants into cohorts based on sarcoma type. That can be useful for describing outcomes in distinct disease groups, but it does not create a randomized comparison. Differences between cohorts may reflect their disease characteristics or other differences rather than any contrast in treatment. The absence of a concurrent control limits what can be inferred about comparative effects.

The record lists multiple secondary outcomes, including response, clinical benefit, survival, adverse events, and participant-reported outcomes. Considering multiple outcomes can provide a broader view of a study, but interpretation requires clarity about which analyses are confirmatory and how multiplicity is addressed. Such details are not reported in the registry record.

Finally, the primary endpoint results and their precision are not reported in the posted information. This underscores why a design description, endpoint definition, and planned enrollment are not substitutes for outcome estimates, analysis denominators, and uncertainty measures. Statistical interpretation depends on all of these elements, as well as transparent reporting of missing data and analysis populations.

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 most direct limitation of the posted record is that it does not report the primary PFS result. It gives the endpoint definition and assessment timeframe, but not the event count, estimated outcome, confidence interval, or analysis denominator. The primary endpoint’s precision therefore cannot be assessed from the registry information.

The single-group design has no randomized control group. It can describe outcomes among participants receiving the regimen but cannot separate treatment effects from other influences or support a direct comparative claim. The two cohorts differ by disease category and are not like-for-like treatment groups.

Several statistical details are not reported in the registry record: the sample-size justification, primary analysis method, analysis populations, missing-data rules, censoring approach, assessment schedule, and multiplicity plan. Their absence from the record does not show that no procedures existed, but it limits independent assessment of how results should be interpreted.

The planned enrollment of 96 differs in purpose from the safety at-risk counts of 42 and 30. The record does not explain the relationship between these figures or give the primary endpoint denominator. It also does not provide individual-level exposure, follow-up duration, or detailed attribution for adverse events and deaths. The listed safety counts and percentages should therefore be treated as descriptive registry summaries, not comparative risk estimates.

The study is listed as active, not recruiting, with a primary completion date of 2025-04-04. The record status and date do not themselves provide evidence about efficacy or safety outcomes. Interpretation remains limited until outcome estimates and their analysis details are reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cabozantinib and Temozolomide for the Treatment of Unresectable or Metastatic Leiomyosarcoma or Other Soft Tissue Sarcoma — NCT04200443.
• Registry record last updated 2026-11-03; status last verified 2026-10.
• Results first posted 2026-05-01.
• 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

NCT04200443 is a phase II, single-group study sponsored by City of Hope Medical Center. It evaluates cabozantinib and temozolomide in people with unresectable or metastatic leiomyosarcoma or other soft tissue sarcomas. Planned enrollment is 96. The study began on 2020-01-22, has a primary completion date of 2025-04-04, and is listed as active, not recruiting.

The primary endpoint is PFS, described as time from treatment start to progression, unequivocal clinical deterioration, or death from any cause. Progression is evaluated using RECIST v1.1, and the record describes calculating the proportion of participants with a PFS event after the first 12 weeks of therapy. The primary outcome estimate and its precision are not reported in the registry record.

Safety summaries cover two disease cohorts and include counts of participants affected by serious and other adverse events, deaths, and selected serious-event terms. The single-group design does not provide a randomized treatment comparison.