Transarterial Chemoperfusion: Cisplatin, Methotrexate, Gemcitabine for Unresectable Pleural Mesothelioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Transarterial Chemoperfusion: Cisplatin, Methotrexate, Gemcitabine for Unresectable Pleural Mesothelioma (NCT02611037), a na phase 2 study. The primary outcome is Disease Control Rate (DCR).

2. Clinical Question

3. Trial Design

This is a phase 2, single-group study registered as NCT02611037. Its title describes transarterial chemoperfusion with cisplatin, methotrexate and gemcitabine for unresectable pleural mesothelioma. The registry lists 34 participants as the enrollment figure, gives the study status as completed, and identifies H. Lee Moffitt Cancer Center and Research Institute as sponsor. The study start date is 2016-03-04 and the primary completion date is 2021-10-16.

The intervention combined cisplatin, methotrexate and gemcitabine. The arm description gives doses of 35 mg/m^2, 100 mg/m^2 and 1000 mg/m^2, respectively, and describes administration every 4 weeks, with a 3-6 weeks interval allowed. A Lung Cancer Symptom Scale for Mesothelioma Questionnaire is also listed as an intervention of type other. The record states that no dose limiting toxicities were observed and that all participants received the same dosing.

The registry lists allocation as NA and masking as none. With a single group and no randomized comparator, outcome changes cannot be separated from the effects of disease course, other care or assessment conditions by a controlled between-group comparison. The lead-in and open-label labels in the safety record do not turn the study into a randomized comparison.

The primary outcome was DCR, defined using partial response and stable disease under modified RECIST for mesothelioma, with a timeframe up to 3 years. Listed secondary outcomes were overall survival, progression free survival, occurrence of treatment related toxicity and quality of life questionnaire scores. The numerical primary outcome and detailed statistical analysis procedures are 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All evaluable participants. Study patients cannot be analyzed separately. No dose limiting toxicities observed, therefore all participants received same dosing.

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 (DCR), measured over Up to 3 years.

The primary endpoint was disease control rate (DCR), expressed as a percentage of participants. The registry defines it as the percentage with partial response plus the percentage with stable disease, assessed using modified Response Evaluation Criteria in Solid Tumors for mesothelioma. The stated timeframe was up to 3 years, and the analysis population was all evaluable participants.

DCR combines two kinds of disease assessment: a partial response indicates a reduction meeting the specified response criteria, while stable disease indicates that the criteria for response or progression are not met. As a general statistical concept, combining these categories can describe the proportion whose measured disease status falls within either category at the assessment used. It does not show how large an individual response was, how long disease control lasted, or what would have happened under a different treatment.

A numerical DCR result, its denominator, and an uncertainty interval are not reported in the registry record. The record therefore supports a description of the endpoint definition, but not an estimate of the observed disease control rate or its precision. The stated population is all evaluable participants; the record also says study patients cannot be analyzed separately.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary percentage outcome: DCR is the percentage of evaluable participants who had partial response plus the percentage who had stable disease. In general, a percentage outcome describes how often a defined category was observed within a stated population. To interpret it, readers need the event definition, analysis population, numerator, denominator and assessment timeframe. The record gives the definition, population as all evaluable participants and timeframe up to 3 years, but does not report a numerical DCR, its numerator or denominator.

What does a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimated outcome. It communicates which values are reasonably compatible with the observed data under the interval method’s assumptions. A narrow interval indicates greater precision than a wide interval, while neither interval width nor the point estimate alone resolves possible bias in study design or outcome measurement. The registry record does not report a confidence interval for DCR, so its statistical precision cannot be assessed.

A confidence interval also does not convert a single-group observation into a controlled treatment effect. It quantifies uncertainty around the quantity being estimated; it cannot provide the missing counterfactual outcome that a randomized comparator can help estimate. Here, the single-group design means that a DCR, even if numerically reported, would describe disease control in the evaluable study population rather than a randomized difference between treatment strategies.

What does the design allow?

Allocation is listed as NA, masking as none, and the model as single group. In general, random allocation helps balance known and unknown prognostic factors between comparison groups. Masking can reduce the influence of knowledge of treatment assignment on care or outcome assessment. These design features address different sources of bias; neither can be presumed when the registry does not list them. This study record does not describe a randomized comparator, so a causal contrast against another treatment is unavailable.

The record’s lead-in and open-label group labels appear in the adverse-event information. They should be read as registry group labels, not as randomized arms or as a basis for direct efficacy comparisons. The record does not provide a statistical comparison between these groups. It states that no dose limiting toxicities were observed and that all participants received the same dosing, but does not report a separate efficacy estimate by group.

How should the planned sample-size illustrations be read?

In general, a sample-size calculation describes the number of participants that a future study might require under specified assumptions about the effect to detect, significance level, allocation and statistical method. It is a planning exercise, not an observed outcome and not proof that an existing study had a particular probability of detecting an effect. The registry’s planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation and effects expressed as fractions of an observed effect. It says that non-time-to-event illustrations are expressed as participants per arm, while time-to-event illustrations give the total number of events.

Those planning assumptions should not be mistaken for this study’s design: the study is listed as single group and has no randomized allocation. The registry record does not report the actual numerical illustration values or a numerical observed DCR from which to assess the effect-based planning premise. Therefore no planned sample size or observed-power claim can be drawn from the record. In general, observed power is not a substitute for reporting an estimate and its uncertainty.

What can be concluded from missing analysis details?

The registry lists five outcome measures and zero analyses. It names secondary outcomes, but does not report a statistical analysis plan, adjustment method, confidence intervals or p-values. In general, a prespecified plan clarifies which outcomes and contrasts are primary, which populations are analyzed, and how uncertainty and multiple testing are handled. Without those details, readers cannot determine whether the reported outcome would be the result of a prespecified analysis or how alternative analyses were addressed. No unreported method should be inferred.

For this endpoint, the record identifies all evaluable participants as the population, but does not state how evaluability was determined or how missing assessments were handled. In general, excluding participants without an assessable endpoint can change the composition of the analysis population, especially if missingness is related to health status or outcome. The record does not report the extent or reasons for missing primary-outcome data, so the direction or size of any resulting bias cannot be evaluated.

Overall, the design and endpoint description establish what the study sought to measure. The absent numerical outcome and analysis details prevent an independent assessment of its estimate, precision and robustness.

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("Chemoperfusion + Questionnaire")
n      <- c(32)
events <- c(24)
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  Chemoperfusion + Questionnaire  32  24  75.0  56.6  88.5  57.9  86.7  57.7  86.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists DCR as the primary outcome and identifies overall survival, progression free survival, treatment related toxicity and quality of life questionnaire scores as secondary outcomes. It reports five outcome measures and zero analyses. A numerical result for the primary endpoint and numerical results for the secondary outcomes are not reported in the registry record.

Multiplicity arises when several outcomes, time points or comparisons are examined. In general, examining more statistical tests can increase the chance of at least one apparently notable result unless the analysis plan addresses that issue. The registry record does not report a multiplicity procedure, a hierarchy among secondary outcomes, or details of which outcome analyses were conducted. No adjustment or testing strategy should therefore be assumed.

The primary outcome population is described as all evaluable participants. The registry does not report the operational definition of evaluability, the number contributing to the primary endpoint, or how missing response assessments were handled. It also does not report reasons for missing data, whether participants with incomplete assessments were excluded, or any sensitivity analysis. In general, missing-data methods depend on why values are missing and on assumptions about outcomes that were not observed; the record does not provide the information needed to assess those assumptions.

The record lists enrollment of 34, but enrollment is not necessarily the primary-outcome denominator. It also says study patients cannot be analyzed separately. The registry does not report whether the outcome was analyzed according to a particular treatment or follow-up population beyond the description “all evaluable participants.” These omissions limit assessment of selection, attrition and the relationship between enrolled participants and the endpoint result.

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: dyspena (40.0%), atrial fibrillation (20.0%), fatigue (20.0%), hypomagnesemia (20.0%), pleural effusion (20.0%).

The registry lists safety information for “Chemoperfusion - Lead In” and “Chemoperfusion - Open Label.” For the lead-in group, it records 5 at risk, 2 with a serious adverse event, 5 at risk for other adverse events, 5 affected for those events, and 2 deaths. For the open-label group, it records 25 at risk, 7 with a serious adverse event, 25 at risk for other adverse events, 25 affected for those events, and 21 deaths. These are the registry’s group-level counts; they should not be treated as a randomized comparison.

The listed serious adverse-event terms and percentages are Dyspena (40.0%), atrial fibrillation (20.0%), fatigue (20.0%), hypomagnesemia (20.0%), pleural effusion (20.0%) and edema limbs (20.0%). The record does not provide additional detail on event timing, recurrence, severity grading or whether each event was judged treatment-related. It also does not state that the recorded deaths were caused by treatment. Counts and listed terms describe what the record reports, not a causal assessment.

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

The registry record establishes the study’s clinical question and endpoint definition: whether transarterial chemoperfusion with cisplatin, methotrexate and gemcitabine was associated with disease control in adults with unresectable malignant pleural mesothelioma. DCR was defined as partial response plus stable disease under modified RECIST for mesothelioma, among all evaluable participants, with a timeframe up to 3 years.

What the record does not establish is the numerical DCR. The primary result, denominator and uncertainty interval are not reported in the registry record. As a result, readers cannot judge the observed rate, how precise it was, or whether the estimate is compatible with a wide range of outcomes. The completed status and study dates do not replace the missing outcome estimate.

Even a reported DCR from this design would be an observed outcome in a single treated group. Without randomized allocation and a control group, it would not establish what would have happened to comparable participants under another treatment or without this intervention. The registry record does not support a comparative treatment-effect estimate.

The safety counts and selected serious-event terms add descriptive information, but they do not establish causation. The record does not detail whether each event was attributed to treatment, and deaths listed by group should not be interpreted as treatment-caused deaths. The record also does not report enough information about follow-up, missing assessments or analysis procedures to resolve the limits of these data.

In general, statistical interpretation requires both an estimate and information about its uncertainty, the population analyzed and the method used. Here, the endpoint and design are described, but the primary estimate and important analysis details are absent from the registry record. Conclusions about efficacy, comparative benefit or treatment-related risk should not be inferred from the available registry entries.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly stated clinical endpoint and the absence of a numerical primary result in the registry record. The DCR definition identifies the response categories and assessment framework, and the record names the evaluable population. Yet the rate, its denominator and its uncertainty are not reported. Without these, readers cannot judge either the magnitude or precision of the outcome.

The study also illustrates the limits of a single-group design. Such a design can document outcomes in participants receiving an intervention, but it cannot provide a randomized estimate of how those outcomes differ from a comparator. The lead-in and open-label safety groupings do not supply that missing comparison. This distinction matters because an observed outcome and a treatment effect are different statistical quantities.

Registry descriptions of enrollment and endpoint populations also serve different purposes. The record lists enrollment of 34 but defines the primary population as all evaluable participants and says study patients cannot be analyzed separately. Because the number evaluable and the endpoint denominator are not reported, readers cannot determine how the enrolled group relates to the primary outcome analysis.

Finally, the record names multiple secondary outcomes while reporting zero analyses and no statistical analysis details. This limits assessment of multiplicity, missing data and analysis choices. Together, these features show why a registry record can describe a study’s intent and design without providing enough outcome information for a quantitative assessment.

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 interpretation is that the registry record does not report a numerical DCR. It also does not report the number of participants contributing to that endpoint or an uncertainty interval. The outcome definition and timeframe are stated, but the observed result and its precision cannot be evaluated.

The study is listed as single group, with allocation NA and no masking. No randomized control group is described, limiting comparative interpretation. The lead-in and open-label safety labels do not provide a like-for-like randomized comparison, and the record does not report a statistical comparison between those groups.

The registry lists enrollment of 34, while the primary population is all evaluable participants and study patients cannot be analyzed separately. The number evaluable, criteria for evaluability, missing assessment counts and handling of missing data are not reported. This leaves uncertainty about which participants contributed to the endpoint and how missing outcomes may affect interpretation.

The record lists secondary outcomes but no analysis entries, and does not report a statistical analysis plan, multiplicity handling, confidence intervals or p-values. Safety information includes group counts and selected serious-event terms, but the registry record does not provide the detailed attribution, timing or assessment information needed to interpret causation. The listed deaths cannot be attributed to treatment from these entries alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Transarterial Chemoperfusion: Cisplatin, Methotrexate, Gemcitabine for Unresectable Pleural Mesothelioma — NCT02611037.
• Registry record last updated 2025-12-18; status last verified 2025-12.
• Results first posted 2023-02-01.
• 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

NCT02611037 is a completed phase 2, single-group study sponsored by H. Lee Moffitt Cancer Center and Research Institute. The registry lists enrollment of 34, a start date of 2016-03-04 and a primary completion date of 2021-10-16. The study evaluated transarterial chemoperfusion with cisplatin, methotrexate and gemcitabine for unresectable malignant pleural mesothelioma.

The primary outcome was DCR, defined as partial response plus stable disease under modified RECIST for mesothelioma, among all evaluable participants and with a timeframe up to 3 years. The numerical DCR and its precision are not reported in the registry record. The record also lists overall survival, progression free survival, treatment related toxicity and quality of life questionnaire scores as secondary outcomes, without reporting numerical results for them.