A Phase II Multi-Strata Study of PM01183 as a Single Agent or in Combination With Conventional Chemotherapy in Metastatic and/or Unresectable Sarcomas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Multi-Strata Study of PM01183 as a Single Agent or in Combination With Conventional Chemotherapy in Metastatic and/or Unresectable Sarcomas (NCT02448537), a non-randomized phase 2 study. The primary outcome is Disease Control Rate.

2. Clinical Question

The study is listed as a Phase II investigation sponsored by Massachusetts General Hospital. Its stated focus was PM01183 alone or combined with conventional chemotherapy in metastatic or unresectable sarcomas. The registry describes three treatment approaches, with eligibility for each approach related to treatment history. That structure is important to interpretation: outcomes across the groups could reflect differences in prior treatment or other group characteristics as well as differences in the regimens. The record does not provide a randomized contrast that would isolate a treatment effect.

3. Trial Design

The registry record identifies this as a Phase II, non-randomized, unmasked, parallel study. Enrollment is listed as 42. The study start is recorded as 2015-08, primary completion as 2017-02, and status as completed. These dates describe the registry record and do not supply a detailed account of when participants were recruited or assessed.

There were three treatment approaches: PM01183 with doxorubicin, PM01183 with gemcitabine, and single-agent PM01183. The descriptions assign these approaches according to prior chemotherapy exposure. Anthracycline-naïve patients were assigned to the doxorubicin combination; patients with prior anthracycline exposure and no prior gemcitabine exposure were described for the gemcitabine combination; and patients previously exposed to both anthracycline and gemcitabine were described for single-agent PM01183. This allocation is not random. Consequently, the groups should not be treated as interchangeable cohorts or as a randomized comparison.

The regimen descriptions give the administration route and frequency within a cycle, but the specific doses are not reported in the registry record. The record identifies metastatic sarcoma as a condition and also describes the intended population as having metastatic and/or unresectable sarcomas. It does not report further eligibility criteria, the distribution of sarcoma subtypes, or baseline clinical characteristics.

The stated primary endpoint was disease control at 24 weeks. The registry defines it by RECIST v1.1 as stable disease or partial response. It also lists overall response rate and treatment-related serious adverse events among secondary outcomes. Although the study status is completed, the endpoint result and secondary outcome results are not reported in the registry record. The registry record also does not report a detailed statistical analysis plan, an explanation of the enrollment target, or a description of interim monitoring.

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: Two participants (one from the PM01183 and Doxorubicin arm and one from the PM01183 alone arm) were not able to be evaluated for response.

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 Disease Control Rate, measured over 24 Weeks.

The primary endpoint is the number of participants who achieved disease control at 24 weeks. Disease control includes either a partial response or stable disease as assessed using RECIST v1.1. The registry definition describes partial response as a decrease of at least 30% in the sum of target-lesion diameters relative to baseline. Stable disease means that changes in tumour measurements meet neither the definition of partial response nor that of progressive disease, using the smallest sum of diameters while on study as the reference.

This endpoint combines two different response states. Partial response represents a specified decrease in measured target lesions, while stable disease indicates that the measurements do not meet the criteria for either response or progression. Combining them gives a count of participants who met either disease-control criterion at the stated assessment time. It does not, by itself, describe how large any response was, how long disease control continued beyond the assessment, or what happened after that time.

A fixed-time endpoint can be useful for describing the proportion or count meeting a defined status at a particular assessment point. It depends on how participants are assessed and on whether outcomes are available at that time. The registry record notes that two participants, one in the PM01183-and-doxorubicin arm and one in the single-agent PM01183 arm, could not be evaluated for response. It does not report how those participants were handled in the primary endpoint analysis or provide the endpoint count. The primary result is therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of endpoint is disease control? Disease control is a binary outcome for each participant: the person either meets the stated definition at the assessment time or does not. The registry reports that the primary measure is a count of participants meeting the definition, rather than a continuous measurement of tumour change. A count can describe the observed outcome, but it does not alone explain the uncertainty around that outcome or establish that a regimen caused it.

In general, an estimate for a binary outcome is most informative when read alongside its denominator and an uncertainty interval. A confidence interval gives a range of values compatible with the data under the statistical method used; it is not a guarantee that the true value lies within that range. Wider intervals generally indicate less precision. The registry record does not report the primary endpoint count, a denominator for its analysis, or a confidence interval, so no such estimate can be interpreted for this endpoint.

Why does the non-randomized design matter? Random allocation is a method for making treatment groups comparable, on average, with respect to measured and unmeasured characteristics. In this study, the treatment approaches are described according to prior anthracycline and gemcitabine exposure. That makes the groups clinically distinct by design. An unadjusted difference between groups, if one were reported, would not by itself identify a causal treatment effect. The registry record does not report an adjusted comparison or the methods that might support one.

The parallel structure means that the treatment approaches were evaluated in separate groups rather than through a crossover design described in the record. The study is unmasked. The record does not report blinding of outcome assessors. For a response endpoint based on imaging criteria, knowledge of treatment assignment can be relevant to assessment procedures, although the record does not give enough detail to determine how assessments were conducted or reviewed.

What does a fixed assessment time capture? The primary endpoint is defined at 24 weeks. A fixed-time binary outcome describes status at that assessment, not the full course of disease over time. It does not indicate how long a participant remained in a response state or when progression occurred. Time-to-event analyses address a different question and require the event and censoring definitions, follow-up information, and analytic methods. These are not reported for the primary endpoint in the registry record.

How should missing assessments be considered? The record says that two participants were not able to be evaluated for response, including one participant from the PM01183-and-doxorubicin arm and one from the single-agent PM01183 arm. This is relevant because the endpoint requires an evaluable response status at the specified time. The registry record does not state whether unevaluable participants were excluded, counted as not meeting disease control, or handled in another way. It also does not report reasons for non-evaluation, other missing assessments, or sensitivity analyses. Different handling choices can affect a binary endpoint estimate, so the analysis population and missing-data rule are essential context.

What can safety counts establish? A count of participants with a serious adverse event describes how many in a reported group experienced an event under the registry’s reporting definitions. A percentage can help convey frequency, but its interpretation depends on the denominator, follow-up, and event-collection rules. Serious adverse events are not synonymous with all adverse events. The record gives group counts at risk and affected, lists selected terms with percentages, and reports deaths by stratum. It does not provide detailed event timing, duration, severity grading beyond serious-event reporting, or exposure-adjusted rates.

In general, adverse-event rates can be affected by how long people are observed and exposed to treatment. When exposure differs, raw counts or simple proportions may not represent comparable risks over time. More detailed safety interpretation could consider follow-up and exposure, but those details are not reported in the registry record. The listed strata also should not be interpreted as randomized treatment comparisons because their treatment histories differ.

What is not available about statistical analysis? A statistical analysis plan would ordinarily specify the analysis population, endpoint calculation, missing-data handling, uncertainty estimates, and any planned comparisons or adjustment methods. The registry record does not report these details and lists no analyses. It is therefore not possible to determine from the record which methods were used for the primary outcome or whether any inferential comparisons were planned or conducted.

The registry includes a sample-size planning description based on an observed effect, with stated general assumptions for significance level, allocation, and approximation. Such calculations are planning illustrations, not evidence about the precision of this study’s observed results and not observed power. No calculated planning values are reported in the registry record. The record also does not report a design justification or explain how an enrollment target was chosen.

Finally, the study lists more than one outcome: disease control is primary, while overall response rate and treatment-related serious adverse events are secondary. When multiple outcomes or comparisons are examined, the chance of at least one apparently notable result can increase unless the analysis plan addresses multiplicity. The registry record does not report a multiplicity strategy, the number of comparisons actually tested, or inferential results. No claim about statistical significance or multiplicity-adjusted evidence can therefore be made from the listed information.

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("PM01183 and Doxorubicin", "PM01183 and Gemcitabine", "Single Agent PM01183")
n      <- c(20, 10, 12)
events <- c(13, 2, 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  PM01183 and Doxorubicin  20  13  65.0  40.8  84.6  43.3  81.9  43.0  81.9
ARM  PM01183 and Gemcitabine  10  2  20.0  2.5  55.6  5.7  51.0  6.0  51.8
ARM  Single Agent PM01183  12  3  25.0  5.5  57.2  8.9  53.2  9.1  53.8

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies disease control at 24 weeks as the primary endpoint and lists overall response rate and treatment-related serious adverse events as secondary outcomes. It does not report a statistical analysis plan, hypothesis tests, or results for these endpoints. The handling of multiplicity is therefore not reported in the registry record. In general, when several outcomes or comparisons are examined, the chance of a false-positive finding can increase; a prespecified testing strategy may address that issue. There is no basis in this record to say whether such a strategy was used.

Response was not evaluable for two participants: one from the PM01183-and-doxorubicin arm and one from the single-agent PM01183 arm. The record does not state whether these participants were excluded from the primary analysis, treated as not achieving disease control, or handled using another rule. Reasons for non-evaluation and any sensitivity analyses are also not reported. This leaves uncertainty about the analysis population and about how missing response assessments might affect the endpoint.

The registry does not report an intention-to-treat definition, a per-protocol population, or another analysis-population definition. It also does not describe interim analyses, stopping rules, or the primary endpoint’s statistical method. These omissions do not establish that such procedures were absent; they mean they are not reported in the registry record. With no endpoint result, analysis denominator, or uncertainty estimate, neither robustness to missing data nor multiplicity-adjusted statistical evidence can be evaluated.

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: neutrophil count decreased (40.0%), white blood cell decreased (15.0%), anemia (10.0%), febrile neutropenia (10.0%), infections and infestations - other, port infection (10.0%).

The serious adverse event figures are reported by registry stratum, with a number at risk and a number affected. Stratum A lists 20 participants at risk and 6 affected; Stratum B lists 10 at risk and 6 affected; Stratum C lists 12 at risk and 4 affected. The record lists zero deaths in each stratum. These are descriptive figures, not randomized comparisons. The registry descriptions do not provide a mapping between the Stratum A, B, and C labels and the named treatment arms, so the strata should not be assigned to treatments based on these figures alone.

The record also lists selected serious adverse event terms with percentages: neutrophil count decreased, 40.0%; white blood cell decreased, 15.0%; anemia, 10.0%; febrile neutropenia, 10.0%; infections and infestations - Other, Port Infection, 10.0%; and intracranial hemorrhage, 10.0%. These percentages describe the registry’s reported terms; the record does not explain their denominator in this listing. They should not be read as incidence estimates for all possible adverse events or as treatment comparisons.

Serious adverse events are a subset of safety outcomes and do not capture every side effect. Follow-up duration, exposure, event timing, and the full adverse-event profile are not reported in the registry record. The figures therefore provide limited descriptive safety information.

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

The registry record documents a completed Phase II investigation of PM01183 as a single agent and in combinations with doxorubicin or gemcitabine. It defines a primary endpoint based on disease control at 24 weeks and describes the treatment approaches in relation to prior chemotherapy exposure. It also reports selected serious adverse event information. These details clarify what the study set out to assess and what aspects of safety were recorded.

The record does not report the primary endpoint result. It therefore cannot establish the observed number achieving disease control, the precision of that result, or whether results differed across the treatment approaches. The lack of a reported result is not evidence that no participant achieved disease control, nor does it indicate that the endpoint was negative. It means the result is not reported in the registry record.

The non-randomized design does not support a direct causal comparison among the regimens. The groups were described according to prior anthracycline and gemcitabine exposure, so they are not equivalent control groups. Any group differences would need to be interpreted in light of that structure and of participant characteristics not reported in the record.

The serious adverse event counts and listed terms offer descriptive safety information, but do not establish a complete safety profile or a comparative risk. The record does not report comprehensive adverse-event results, exposure-adjusted comparisons, or detailed follow-up. The listed zero deaths in each stratum is a registry observation, not a statement about other serious harms.

In general, a clinical trial result is most useful when its estimate, uncertainty, analysis population, missing-data handling, and design limitations are all clear. Here, the endpoint definition and some safety figures are available, but the primary outcome result and important analysis details are not reported in the registry record. Conclusions should remain limited to those documented features.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why treatment-group structure matters as much as the names of the treatments. The three approaches were linked to different prior chemotherapy histories. Because allocation was non-randomized, treatment groups cannot be treated as exchangeable, and simple contrasts would not by themselves isolate treatment effects. Recognizing that distinction prevents descriptive group results from being mistaken for a controlled comparison.

The primary endpoint also illustrates the difference between an outcome definition and an outcome result. The record gives a specific assessment time and a RECIST-based definition that combines partial response and stable disease. That makes the intended measure understandable, but without the observed endpoint count, denominator, and uncertainty, its magnitude and precision cannot be evaluated. A completed study status does not supply those missing statistical results.

The record’s note about participants who could not be evaluated for response highlights why analysis populations and missing-data rules matter for binary endpoints. If an outcome is unavailable, the treatment of that participant can influence the estimated count or proportion. Since the registry does not report the handling rule, readers cannot determine how the endpoint analysis addressed this issue.

The safety information similarly demonstrates the value and limits of descriptive counts. Serious adverse event figures and selected event terms can communicate what was recorded, while still leaving unanswered questions about duration of observation, exposure, and the full set of events. Taken together, these features make the study a useful case for separating what a registry defines, what it reports numerically, and what remains unavailable for statistical interpretation.

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 efficacy is that the registry record does not report the disease-control result, its analysis denominator, or an uncertainty interval. The record notes two participants who were not evaluable for response, but does not explain how they were handled. It also does not report other missing assessments or sensitivity analyses.

The non-randomized allocation and treatment-history-based strata limit comparisons across regimens. The registry record does not report baseline characteristics or adjusted analyses that might help account for differences among the groups. It also does not map the safety stratum labels to the named treatment arms in the reported adverse-event figures.

Further limitations are that the specific predetermined doses are not reported, nor are detailed eligibility criteria, sarcoma subtype distributions, assessment procedures, follow-up beyond the primary time point, or duration of treatment exposure. The record lists overall response rate and treatment-related serious adverse events as secondary outcomes but does not report their results. Detailed adverse-event summaries and the denominator for the listed serious-event term percentages are not reported.

Finally, the registry record does not report a statistical analysis plan, the method used for the primary endpoint, a multiplicity strategy, or a rationale for the enrollment target. These absences limit assessment of analytic choices and precision; they do not establish that procedures were not conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase II Multi-Strata Study of PM01183 as a Single Agent or in Combination With Conventional Chemotherapy in Metastatic and/or Unresectable Sarcomas — NCT02448537.
• Registry record last updated 2021-03-03; status last verified 2021-02.
• Results first posted 2018-03-05.
• 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

NCT02448537 is a completed, non-randomized, unmasked Phase II parallel study sponsored by Massachusetts General Hospital. It evaluated PM01183 alone or in combination with doxorubicin or gemcitabine in metastatic and/or unresectable sarcomas. The treatment descriptions distinguish participants by prior chemotherapy exposure. Enrollment is listed as 42; the study start is 2015-08 and primary completion is 2017-02.

The primary endpoint was the number of participants with disease control at 24 weeks under RECIST v1.1. The registry record does not report the primary endpoint result or its analysis method. It notes two participants who could not be evaluated for response. Selected serious adverse event counts and terms are reported, but the record does not provide a complete safety analysis or detailed statistical plan.