Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma (NCT01112293), a na phase 2 study. The primary outcome is 3-month Progression Free Survival Rate.

2. Clinical Question

3. Trial Design

This was a phase II, single-group, multi-site study of GC1008 in relapsed malignant pleural mesothelioma. The registry record lists the trial status as completed and enrollment as 14. Its brief summary describes a plan to enroll approximately 40 people at the University of Pennsylvania and the University of Chicago, with about 20 subjects expected at each institution. The reason that listed enrollment differs from the planned enrollment described in the summary is not reported in the registry record.

The arm description states that all subjects received GC1008 in 3 week cycles. Allocation is listed as NA, masking as none, and the study model as single group. These features mean that the record describes no randomized assignment and no separate control arm. It therefore presents a treatment-group outcome, not a randomized comparison between GC1008 and another treatment or no treatment.

The registry lists the study start as 2010-04 and primary completion as 2012-10. It gives the primary outcome timeframe as 3 months. These dates and the endpoint timeframe do not establish how long each participant was followed, when progression was assessed, or what follow-up procedures were used; those details are not reported in the registry record.

The brief summary frames the study as an evaluation of safety and effectiveness, and the listed secondary outcome concerns toxicity and safety of systemic infusion. The record does not provide dosing details, eligibility criteria, outcome-assessment procedures, or a statistical analysis plan. It also does not state a sample-size justification. The trial's observed enrollment and the outcome analysis population should therefore be kept distinct when interpreting the registry entry.

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

Analysis population for the primary outcome, as defined in the registry: Outcome analysis presented in manuscript of results of trial based on 13 participants.

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 3-month Progression Free Survival Rate, measured over 3 months.

The primary endpoint is the 3-month progression-free survival rate. The registry describes it as the fraction of subjects surviving 3 months without disease progression and records the measure as a count of participants. In practical terms, the endpoint asks how many people in the outcome population met both conditions at the stated timepoint: being alive and having no disease progression.

In general, a progression-free survival endpoint is used to describe disease control over a defined period. A fixed-time rate gives a proportion at a particular time rather than a summary of how long participants remain progression-free across all follow-up. It can be straightforward to interpret, but it depends on clear definitions of progression, consistent assessment, and appropriate handling of participants whose status at the timepoint is unknown. Those operational details are not reported in the registry record.

The endpoint timeframe is 3 months. The registry says the outcome analysis presented in the trial manuscript was based on 13 participants, but it does not report the number who met the endpoint, the rate, or an uncertainty interval. No endpoint result can be inferred from the enrollment count alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary outcome: participants either met the stated condition at 3 months or did not. The outcome is also expressed as a count of participants, and its description defines the target as surviving 3 months without disease progression. The actual count and rate are not reported in the registry record. Because those results are missing, the endpoint cannot be numerically interpreted from the registry entry.

What does a fixed-time rate describe?

In general, a fixed-time rate is the share of an analysis population that meets a specified outcome condition by a particular timepoint. It answers a question about status at that timepoint, rather than describing the full pattern of time until an event across follow-up. For a progression-free survival endpoint, the condition combines survival and no progression through the specified time. Its interpretation depends on how progression is defined and assessed, and on how people without an ascertainable status at the timepoint are handled. Those details are not reported in the registry record.

Why does the analysis population matter?

The registry lists enrollment of 14 and says the outcome analysis in the trial manuscript was based on 13 participants. These figures refer to different stated populations: overall enrollment and the population described for the outcome analysis. The reason for the difference, the disposition of participants, and the rules for inclusion in the outcome analysis are not reported in the registry record. A reader should not assume a reason for the difference or treat the full enrollment count as the endpoint denominator.

In general, an analysis population needs to be defined before interpreting a proportion. The denominator determines which participants contribute to the estimate, while missing or unavailable outcome statuses can affect both the estimate and its precision. If outcomes are unavailable, possible analysis choices include excluding those participants or making assumptions about their status; these choices can lead to different answers. The registry does not state how missing endpoint information was handled.

How should uncertainty be considered?

In general, a confidence interval presents uncertainty around an estimated quantity under stated statistical assumptions. For a binary outcome, an interval around a rate helps show how much uncertainty remains about the underlying rate, rather than presenting the observed fraction as exact. The choice of interval method can matter, particularly with a small analysis population. The registry record does not report a primary endpoint estimate, confidence interval, or method for calculating one, so no numerical precision assessment is available from this entry.

A hypothesis test, when used, addresses a specified statistical question under a model. Its meaning depends on the comparison or reference value, the analysis population, and the assumptions used. The registry's listing of 0 analyses does not establish which tests were or were not conducted for the manuscript. A statistical plan, hypothesis, test, and result are not reported in the registry record.

What does the design imply for inference?

The study is listed as single group, with allocation NA and masking none. In general, a single-group study can describe outcomes in the group receiving the study intervention, but it does not provide a concurrent randomized control for estimating a treatment contrast. Without such a comparison, observed outcomes cannot be separated statistically from other explanations using the trial record alone. This limitation applies even if a group outcome is reported precisely.

The trial is labeled phase II, but that designation does not supply the statistical design or a sample-size justification. Such a justification, along with any interim-analysis plan, stopping rule, or detailed analysis plan, is not reported in the registry record. No assumptions about those features should be made based on the phase label.

How do the planning illustrations differ from trial results?

In general, sample-size planning asks how many participants might be needed under specified assumptions to detect a target effect with a chosen error rate and power. The planning assumptions associated with this study describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe hypothetical two-arm planning illustrations based on a stated fraction of an observed effect; they are not the design used in this single-group trial. The illustrations are planning scenarios, not observed power, and should not be mistaken for the number enrolled or an analysis of the study results.

The record also distinguishes total events for time-to-event planning from participants per arm for other planning calculations. Such planning conventions do not add information about the trial's observed endpoint. Since the primary outcome result and its uncertainty are not reported in the registry record, planning assumptions cannot substitute for the missing estimate or establish what the trial found.

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("Investigational Drug infusion-for Safety and Effec")
n      <- c(13)
events <- c(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  Investigational Drug infusion-for Safety and Effec  13  3  23.1  5.0  53.8  8.2  50.3  8.4  50.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 0 analyses. These entries do not identify which outcomes were treated as primary for statistical testing, how many hypotheses were tested, or whether any adjustment for multiple comparisons was used. The analysis plan and multiplicity strategy are not reported in the registry record.

In general, testing multiple outcomes can increase the chance that at least one result appears noteworthy by chance, depending on the testing strategy and the relationships among outcomes. Adjustment procedures can address some of that issue, but their use and appropriateness depend on the prespecified questions and analysis plan. The registry's outcome and analysis counts alone do not show whether multiplicity was a concern or how it was handled.

The primary outcome description says the manuscript analysis was based on 13 participants, whereas overall enrollment is listed as 14. The reason for the difference, participant disposition, and the handling of missing or unassessable outcomes are not reported in the registry record. The record does not say whether the analysis population was defined by intention to treat, by treatment received, or by another rule. Those terms should not be assigned to the study without documentation.

In general, missing outcome data can affect an estimate if the people with unavailable assessments differ from those with known outcomes. The extent of missingness, reasons for any missing data, and methods used to address it are not reported in the registry record. The registry also does not provide a primary endpoint count or rate with which to assess the impact of missing data. These gaps limit interpretation of both the result and its precision.

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: neoplasms benign, malignant and unspecified (incl cysts and polyps) (14.3%), disease progression (14.3%), nausea (7.1%), hyponatremia (7.1%), fatigue (7.1%).

The registry lists 14 participants at risk for serious adverse events, of whom 6 were affected. It also lists 14 participants at risk for other adverse events, of whom 12 were affected. The record lists 12 deaths. These are registry counts; the entry does not establish that the events or deaths were caused by GC1008.

Among the listed serious-event terms, the record gives Neoplasms benign, malignant and unspecified (incl cysts and polyps) as 14.3%, Disease Progression as 14.3%, and Nausea, Hyponatremia, Fatigue, and Thrombosis as 7.1% each. These term-specific percentages should be read as the registry reports them, not as a comparison with another group or a causal estimate.

In general, adverse-event counts describe events recorded under the study's reporting rules. They do not on their own distinguish events caused by treatment from events due to the underlying condition or other factors. The registry does not report attribution details, event timing, duration, severity grading, or a comparison group for assessing relative safety. The deaths entry does not specify cause or relationship to treatment.

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

The registry record describes a completed phase II study of GC1008 in relapsed malignant pleural mesothelioma, conducted as a single group. Its primary question concerns the number of participants alive without disease progression at 3 months. However, the record does not report the endpoint count or rate. It therefore cannot support a numerical statement about the primary outcome.

Even if a single-group outcome estimate were available, it would describe the observed participants and would not establish how outcomes would have differed under another treatment or no study intervention. In general, a comparative effect requires an appropriate contrast and analysis. This record lists no comparator arm and no randomized allocation, so no treatment difference can be estimated from the registry entry.

The registry describes the outcome analysis as based on 13 participants and lists 14 participants enrolled. The reason for the difference is not reported. The estimate's denominator, handling of missing outcome information, and statistical uncertainty are therefore not fully documented in the record. No confidence interval for the primary outcome is reported.

The safety entries report counts of participants affected by adverse events and a count of deaths, along with several event terms and percentages. These entries are useful as descriptive information, but they do not establish causality or comparative risk. The registry does not report the information needed to determine whether an event was considered related to the investigational drug.

In general, absence of a result in the registry record is not evidence that an outcome did or did not occur. The record's intended endpoint and design can be described, but the missing primary result prevents a direct assessment of the observed 3-month outcome. No conclusion about benefit, lack of benefit, or clinical use follows from the information recorded.

14. Why This Trial Matters Statistically

This study illustrates why the design and the reported analysis population matter when reading a clinical outcome. The registry describes 14 enrolled participants and an outcome analysis based on 13 participants. Without the reason for that difference or a reported endpoint denominator, a reader cannot assume which participants contributed to the primary estimate.

It also illustrates the distinction between a fixed-time endpoint and a comparative treatment effect. The primary question is framed as progression-free survival at 3 months, but the study has a single group and no concurrent comparator. In general, a group rate can describe what occurred among participants in that group, while a comparative design is needed to estimate how outcomes differ between treatment strategies under the study's assumptions.

Safety entries are another useful teaching point. Counts of participants affected and listed adverse-event terms summarize recorded events, but they do not establish causality. Without a control group and attribution information, the registry figures cannot distinguish drug-related events from other explanations.

Finally, the record separates a planned study population from actual listed enrollment: the brief summary describes approximately 40 expected participants, while the enrollment field lists 14. The reason is not reported in the registry record. Comparing planning statements with actual enrollment can help readers recognize that a target or expectation is not itself an observed result or evidence about why enrollment differed.

These features make transparent reporting especially important: outcome counts, denominators, missing-data handling, uncertainty estimates, and analysis methods are needed to assess what a small single-group study can establish. Several of those details are not reported in the registry record.

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 registry record does not report the primary endpoint result, even though it identifies the 3-month progression-free survival rate as the primary outcome. It also does not report a confidence interval or the method used to estimate uncertainty. This prevents a direct assessment of the observed outcome and its precision.

The listed enrollment is 14, while the outcome analysis is described as based on 13 participants. The reason for that difference, participant disposition, endpoint denominator, and handling of missing outcomes are not reported in the registry record. The analysis population cannot be characterized further from the entry.

The study is single group, with allocation listed as NA and masking as none. No comparator is described, limiting the ability to interpret an observed group outcome as a treatment effect relative to another approach. The record does not report an analysis plan, sample-size justification, interim-analysis plan, or multiplicity strategy. Its listing of 8 outcome measures and 0 analyses does not resolve those gaps.

The record provides limited detail about the intervention and endpoint procedures. Dose, treatment duration, progression-assessment procedures, follow-up beyond the endpoint timeframe, and operational definitions are not reported in the registry record. These details can affect interpretation of both efficacy outcomes and adverse events.

For safety, counts and event terms are listed, but causal attribution, event timing, and the causes or treatment relationships of the 12 deaths are not reported. These limitations mean that the registry supports a basic description of the study but not a full evaluation of its outcome estimates or safety profile.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Anti-TGF Monoclonal Antibody (GC1008) in Relapsed Malignant Pleural Mesothelioma — NCT01112293.
• Registry record last updated 2020-04-10; status last verified 2020-03.
• Results first posted 2020-04-10.
• 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 a completed phase II, multi-site, single-group study of GC1008 in relapsed malignant pleural mesothelioma. It lists enrollment of 14 and describes treatment with GC1008 in 3 week cycles. Allocation is listed as NA and masking as none.

The primary outcome is the 3-month progression-free survival rate, described as surviving 3 months without disease progression. The registry says the outcome analysis presented in the trial manuscript was based on 13 participants, but the primary result and its precision are not reported. The reason for the difference between enrollment and the analysis population is not reported in the registry record.

The safety entry lists 6 participants affected by serious adverse events, 12 affected by other adverse events, and 12 deaths. These counts do not establish causality. The record lists 8 outcome measures and 0 analyses, but does not report the statistical analysis plan, missing-data methods, or multiplicity approach.