Nab-Sirolimus and Pazopanib Hydrochloride in Treating Patients With Advanced Nonadipocytic Soft Tissue Sarcomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Nab-Sirolimus and Pazopanib Hydrochloride in Treating Patients With Advanced Nonadipocytic Soft Tissue Sarcomas (NCT03660930), a na phase 1, phase 2 study. The primary outcome is Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs).

2. Clinical Question

The study examined a combination of nab-sirolimus and pazopanib in people with advanced nonadipocytic soft-tissue sarcomas. Its primary endpoint concerned dose-limiting toxicities (DLTs) during the first 2 cycles. The record defines a DLT using the severity of an adverse event and its possible relationship to either or both study drugs. This endpoint addresses tolerability during the specified early treatment period; it is not itself a measure of tumor response or survival.

The registry lists secondary outcomes covering adverse events, progression-free survival, overall survival, response, disease control, and duration of response. These outcomes address different aspects of safety and disease status, but the record does not provide results for them in the registry record. In particular, the number of participants who experienced DLTs is not reported in the registry record. The listed serious adverse event figures therefore cannot be substituted for the primary endpoint: the definitions and reporting categories are not shown to be equivalent.

3. Trial Design

This was a phase 1/2, single-group study sponsored by the University of Washington. The registry lists enrollment of 19, no masking, and allocation as not applicable. It was marked terminated. The study start date is 2019-04-01, and the primary completion date is 2022-11-17; the reason for termination is not reported in the registry record.

Participants received the combination of nab-sirolimus and pazopanib. The arm description says nab-sirolimus was administered intravenously on days 1 and 8, or on day 1 only, and pazopanib hydrochloride was taken orally daily on days 1-21. Cycles were described as repeating every 21 days. The recorded continuation language refers to unequivocal clinical disease progression and unacceptable toxicity, then ends during a clause about the investigator’s opinion. The remaining stopping language is not reported in the registry record.

The cohort listings show several named cohorts and dose levels, but the record does not report the protocol’s dose-selection rules or a complete explanation of how participants entered each cohort. It would therefore be unwarranted to infer a particular escalation design or to interpret the cohort labels as proof of a specific decision algorithm.

With no control group and no random allocation, the study does not provide a like-for-like comparison between the combination and another treatment. Its single-group structure can describe observed outcomes among participants treated in the study, but it cannot isolate the effect of either drug or the combination from other explanations. The record does not report a sample-size justification, a detailed statistical analysis plan, or an explanation for termination.

4. Participant Flow and Accounting

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

Before assignment: No participants were enrolled in Phase II of the study.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: MTD was determined to be ABI-009 on DAY 1 of a 21 day cycle ONLY in combination with daily oral pazopanib.

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 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs), measured over First 2 cycles (3-week cycles, 21 days each).

The primary endpoint is the number of participants who experienced dose-limiting toxicities during the first 2 cycles, with each cycle described as 21 days. The registry defines a DLT as an adverse event of Grade 3 or greater that is at least possibly related to either or both nab-sirolimus and pazopanib. It also includes any death not clearly due to the underlying disease or extraneous causes, and persistent intolerable nonhematologic adverse events of any grade that, in the investigator’s opinion, require dose reduction or permanent discontinuation. A toxicity may be considered non-DLT only when a clearly identified and documented alternative explanation exists.

General statistical context: In early-phase treatment research, a DLT endpoint focuses attention on serious or treatment-limiting events over a defined initial period. It is a count of participants meeting the endpoint definition, rather than a comparison of treatment groups. The definition matters: event severity, attribution, persistence, and decisions about dose changes all affect classification.

The registry record specifies the endpoint and its timeframe, but does not report the observed number of participants with DLTs. The serious adverse event figures elsewhere in the record do not establish the primary endpoint result. They use a separate reporting category, and the record does not state that every serious event met the DLT definition or that every DLT was a serious adverse event.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group phase 1/2 study and names the number of participants who experienced DLTs as the primary outcome. The tables and plots present posted information without turning a one-group record into a randomized comparison. The key statistical task is to keep the endpoint definition, the reporting period, and the cohort-specific safety listings distinct.

What does a participant count represent?

The primary outcome is a count of participants who meet the DLT definition during the first 2 cycles. A participant count is not the same as a count of all adverse events: one participant may experience more than one event, while the endpoint is phrased in terms of participants. The record does not report the DLT count, so no primary endpoint rate or count can be described from the available result information.

General statistical context: Counts are often useful for describing how many people in a defined group experienced an outcome. If the group is small, each participant’s outcome can have a noticeable effect on the descriptive summary. A count alone also does not express uncertainty around an underlying event probability. Confidence intervals can express a range of estimates compatible with the observed data under a statistical model; no such interval for the primary endpoint is reported.

Why does the DLT definition matter?

The registry’s definition includes several criteria: event grade, possible relation to either or both drugs, the possibility of certain deaths, and persistent intolerable nonhematologic events that require dose reduction or permanent discontinuation in the investigator’s opinion. It also allows a toxicity to be deemed non-DLT when a clearly identified and documented alternative explanation exists. These details affect which events count toward the endpoint. The record does not provide participant-level event adjudications, so the reader cannot independently apply the definition to the separate adverse event listings.

The timeframe is also part of the endpoint. The primary outcome refers to the first 2 cycles, with cycles specified as 21 days each. Safety figures presented by cohort should not be assumed to cover precisely this period unless the record states that they do. The posted endpoint description does not establish that relationship for the cohort safety listings.

How should the cohort safety listings be read?

The adverse event data are organized into named cohorts and dose levels, with participants at risk, participants affected by serious events, participants affected by other events, and deaths listed separately. These categories answer different descriptive questions. A serious adverse event count does not automatically equal the number meeting the DLT definition, and a death count does not specify cause or drug relationship. No aggregation across cohorts is necessary to describe the posted entries, and a combined estimate should not be inferred from them without a defined analysis and appropriate context.

The serious event terms are displayed with percentages, each listed as 50.0%. Those values should be read as registry-displayed figures. The record excerpt does not explain their calculation or provide further context for denominators, so this page does not recalculate or reinterpret them. Similarly, the cohort-level counts are not evidence of a between-dose trend; the study has no randomized comparison, and the record does not report an analysis comparing these groups.

What can a single-group design estimate?

General statistical context: A single-group study can describe outcomes observed among enrolled participants. Without a concurrent comparator, it cannot separate the treatment experience from other influences or estimate a treatment contrast in the same way as a randomized comparison. Here, allocation is listed as not applicable, masking as none, and the model as single group. The record itself cautions that there is no like-for-like control comparison.

The cohort labels and dose levels indicate that the record contains multiple named groups, but they do not establish that these groups were randomized or comparable. Differences in their observed entries should therefore not be read as causal evidence that one dose level changes risk relative to another. Details of assignment, dose-selection decisions, and the planned inferential analysis are not reported in the registry record.

What is not available for statistical assessment?

The record lists 13 outcome measures and 0 analyses. It does not report the primary DLT result, confidence intervals, hypothesis tests, missing-data procedures, analysis populations, or the statistical plan. The number of enrolled participants is listed as 19, but the available cohort entries do not provide a complete account of how all enrolled participants contributed to each outcome. No inference about the unlisted outcomes or about participants without a posted result is justified.

General statistical context: When several outcomes are considered, multiplicity refers to the risk of misleading findings arising from multiple statistical tests or repeated opportunities to detect a result. A plan may specify how outcomes are prioritized or how testing is controlled, but that information is not reported. The list of outcomes alone does not show which were formally tested or how results were interpreted. Likewise, a sample-size illustration is a planning exercise, not observed power and not a substitute for the trial’s own design justification. The registry record does not report that justification.

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, Dose Level 0", "Cohort 4, Dose Level -1", "Cohort 5, Dose Level -2", "Cohort 6, Dose Level 0B", "Cohort 9, Dose Level -1B", "Cohort 10, Dose Level -2B")
n      <- c(2, 2, 2, 2, 2, 3)
events <- c(2, 2, 2, 2, 2, 2)
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, Dose Level 0  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  Cohort 4, Dose Level -1  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  Cohort 5, Dose Level -2  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  Cohort 6, Dose Level 0B  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  Cohort 9, Dose Level -1B  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  Cohort 10, Dose Level -2B  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including the primary DLT outcome and secondary measures of adverse events, progression-free survival, overall survival, response, disease control, and duration of response. It lists 0 analyses. The statistical plan, including any rules for prioritizing outcomes or addressing multiplicity, is not reported in the registry record. The outcome list should not be treated as evidence that every measure was analyzed or formally tested.

General statistical context: Multiplicity matters when many outcomes or statistical tests are examined, because repeated testing can increase the chance of apparently notable findings. A prespecified analysis plan can clarify which outcomes are primary, how secondary outcomes are interpreted, and whether any adjustment is used. Those details are not available. No adjustment method or testing hierarchy should be inferred.

The record does not report how missing outcome data were handled, how participants who discontinued treatment were included in analyses, or which analysis populations were used. It also does not explain whether every enrolled participant contributed to each outcome. Enrollment is listed as 19, but that figure alone does not establish the number assessed for the primary endpoint or for each secondary outcome.

The registry status is terminated, but the reason for termination and its implications for outcome completeness are not reported. The record also does not provide a sample-size justification or a statistical analysis plan. These omissions limit assessment of whether the available outcome reporting matches the intended analyses and how incomplete follow-up, if any, was treated.

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: cardiac disorders, other: tricuspid valve mass (50.0%), non-cardiac chest pain (50.0%), skin ulceration (50.0%), confusion (50.0%), platelet count decreased (50.0%).

The serious adverse event listings are organized by cohort and dose level. For each cohort, the record shows participants at risk, participants affected by serious events, participants affected by other events, and deaths. The listed cohorts have 2 or 3 participants at risk. These are small cohort-specific counts and should be read as descriptions of the posted entries, not as stable estimates for a broader population.

The record lists one death in Cohort 10, Dose Level -2B, and zero deaths in the other displayed cohorts. It does not report the cause of this death or whether it was considered related to treatment or met the primary DLT definition. The serious event terms shown are Tricuspid valve mass, Non-cardiac chest pain, Skin Ulceration, Confusion, Platelet Count Decreased, and Urinary Tract Infection; each is displayed as 50.0%. The registry information does not explain those percentages further.

Serious adverse events and DLTs are not interchangeable categories. The primary endpoint has its own severity, attribution, and treatment-limiting criteria, while the serious event listings are separate safety summaries. The DLT count is not reported in the registry record, so it cannot be inferred from these listings. No comparison between cohorts or causal attribution should be drawn from these figures alone.

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

The record establishes that this was a phase 1/2, single-group study of nab-sirolimus with pazopanib for advanced nonadipocytic soft-tissue sarcomas. It specifies a primary DLT endpoint and its first-2-cycle timeframe, and it presents serious adverse event information for named cohorts. It also lists secondary outcomes related to survival, response, disease control, and adverse events.

However, the primary endpoint result is not reported in the registry record. The posted information therefore does not show how many participants experienced DLTs. The serious adverse event entries cannot fill that gap because the record does not state that those entries are equivalent to DLTs. The listed one death in Cohort 10 is not accompanied by a cause or attribution, and it cannot be assumed to be treatment-related or to meet the DLT definition.

The study had no randomized comparator and no masking. Its design can describe outcomes recorded among participants, but it cannot establish a comparative treatment effect. The listed survival and tumor response outcomes do not have numerical results in the information, so no conclusion about those outcomes is supported by the registry entries.

The record’s terminated status is also not an explanation of why the study ended. The reason for termination, the completeness of outcome follow-up, the missing-data approach, and the analysis populations are not reported. These uncertainties constrain what can be inferred from the registry record. The cohort counts remain descriptive observations, not evidence that a particular dose level is safer or more effective than another.

In short, the posted record documents the study question, treatment combination, endpoint definition, and selected safety entries. It does not provide the primary DLT result or enough comparative and analytic information to support broader conclusions. The absence of a reported result should not be interpreted as a finding of no events or no effect.

14. Why This Trial Matters Statistically

This study is statistically instructive because its primary endpoint is a clearly defined participant count over a specified early treatment period, while the corresponding result is not reported in the registry record. It illustrates why an endpoint definition and an endpoint result are separate pieces of information. Knowing what was to be counted does not reveal how many participants met the criteria.

It also shows why safety categories should not be collapsed. The DLT definition includes severity, possible relationship to study drugs, certain deaths, and treatment-limiting toxicity. The cohort listings separately display serious events, other events, and deaths. Treating these as interchangeable would obscure the distinctions built into the endpoint and could overstate what the record shows.

The single-group design is another important feature. Without a randomized comparator, the posted results can describe the treatment group but cannot offer a like-for-like control comparison. The multiple cohort labels do not change that limitation, and their observed counts should not be interpreted as randomized dose comparisons. Small cohort counts also warrant descriptive rather than expansive interpretation.

Finally, the record lists numerous outcome measures but no analyses. Without a reported statistical plan, analysis populations, missing-data methods, or numerical outcome results, readers cannot assess how the stated outcomes were analyzed or how uncertainty was handled. These are general considerations in reading clinical trial registries, and they directly define the boundary between what is documented and what remains unknown.

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 important trial-specific limitation for interpreting this record is that the primary outcome is defined but its observed result is not reported. The record therefore does not show the number of participants experiencing DLTs during the first 2 cycles. The cohort safety listings do not resolve this gap, because the registry does not establish that serious adverse events correspond to the DLT definition or timeframe.

The study is single group, with allocation listed as not applicable and no masking. There is no randomized comparator for a like-for-like assessment. The cohort and dose-level labels do not, on their own, establish how assignment occurred or whether groups were intended to be compared. The record does not report the dose-selection rules or a detailed protocol explanation for the cohorts.

Enrollment is listed as 19, while the displayed cohort entries include small numbers at risk. The available information does not describe how all enrolled participants contributed to each outcome. Analysis populations, follow-up completeness, and missing-data procedures are not reported. Nor are the statistical analysis plan, multiplicity procedures, confidence intervals, or hypothesis tests for the primary outcome reported.

The study is marked terminated, but the reason for termination is not reported in the registry record. That status cannot identify the cause of stopping or establish whether it affected outcome reporting. The arm description also ends mid-sentence after an investigator-discretion clause, so the remaining stopping language is not available.

Finally, the serious event percentages are displayed as 50.0%, but the record information does not explain their calculation. These percentages should not be reinterpreted or compared beyond what is explicitly listed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Nab-Sirolimus and Pazopanib Hydrochloride in Treating Patients With Advanced Nonadipocytic Soft Tissue Sarcomas — NCT03660930.
• Registry record last updated 2025-04-30; status last verified 2025-04.
• Results first posted 2024-03-13.
• 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

The registry record describes NCT03660930, a phase 1/2, single-group study of nab-sirolimus with pazopanib hydrochloride in advanced nonadipocytic soft-tissue sarcomas. The sponsor is the University of Washington. Enrollment is listed as 19; masking is listed as none, and allocation as not applicable. The record gives a start date of 2019-04-01, a primary completion date of 2022-11-17, and status as terminated.

The primary outcome is the number of participants experiencing DLTs during the first 2 cycles, each described as 21 days. The registry defines DLT criteria but does not report the observed primary endpoint count. It lists 13 outcome measures and 0 analyses. Cohort-specific serious adverse event information is displayed, including one death in Cohort 10, Dose Level -2B; the cause and treatment relationship are not reported.

The termination reason, statistical analysis plan, analysis populations, and missing-data procedures are not reported in the registry record. The single-group design has no randomized comparator, limiting comparative interpretation.