Phase II Study of Alimta (Pemetrexed) Treatment of Advanced Thymoma and Thymic Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study of Alimta (Pemetrexed) Treatment of Advanced Thymoma and Thymic Carcinoma (NCT00198133), a non-randomized phase 2 study. The primary outcome is Objective Response Rate (Complete and Partial Response).

2. Clinical Question

This is a single-arm efficacy question: among participants with a post-baseline measurement, what proportion met the stated response definition while receiving pemetrexed? It is not a question about whether pemetrexed outperforms another treatment, because the record lists no comparison arm. Nor does the stated endpoint alone answer how long a response lasted or how treatment-related harms compare with those under another regimen.

The record lists 27 enrolled participants, while the endpoint population is described as 26 evaluable participants. Those figures refer to different recorded aspects of the study; the registry record does not explain the reason for the difference. The clinical question therefore needs to be read alongside the population definition and the absence of a reported endpoint analysis. The planned question is clear, but the posted record does not give the result needed to estimate the observed response proportion.

3. Trial Design

The registry classifies this as a Phase II, non-randomized, single-group study with no masking. It is listed as completed. Enrollment is recorded as 27. The study is titled as an evaluation of Alimta, or pemetrexed, in advanced thymoma and thymic carcinoma, and the brief summary describes the purpose as studying single-agent efficacy in thymic cancers.

The intervention arm is named Pemetrexed. Its description specifies an infusion once every 21 days, with each interval treated as one cycle. The registry record does not state a dose in the arm description. With one study group and no random allocation, there is no internal randomized control group against which to estimate a treatment contrast. The record also gives no masking method beyond listing masking as none.

The study start is recorded as 2005-01 and primary completion as 2006-12. These dates describe the registry timeline; they do not establish when each participant began treatment, how long any individual was followed, or when the analysis was performed. The primary endpoint timeframe is listed as up to 3 years.

The primary endpoint population is defined as patients with at least one post-baseline measurement, with 26 evaluable participants noted: 15 with thymoma and 11 with thymic carcinoma. The enrollment figure and evaluable population should not be treated as interchangeable. The registry record does not explain why a participant counted in enrollment was not included in that endpoint population, nor does it provide an analysis population flow.

Secondary outcomes listed are duration of remission and Grade 3/4 treatment-related adverse events. The record lists 3 outcome measures, but it does not report outcome analyses. In particular, the registered design and endpoint definitions describe what was intended to be assessed; they do not by themselves establish the observed response, duration of remission, or treatment effect.

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 patients with at least one post baseline measurement. (26 evaluable - 15 T and 11 TC patients)

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 Objective Response Rate (Complete and Partial Response), measured over Up to 3 years.

The primary endpoint is the objective response rate, expressed as the percentage of participants with a complete or partial response. It is a binary-outcome measure at the participant level: each participant is classified according to whether the specified response occurred, and the rate describes the proportion meeting that definition in the endpoint population.

The registry description specifies RECIST v1.0 and states that an objective response requires at least a 30% decrease in the sum of the longest diameter of target lesions relative to baseline longest diameter. The endpoint population is described as all patients with at least one post-baseline measurement. The response timeframe is listed as up to 3 years.

A response endpoint is used to summarize tumor response under a prespecified classification rule. The rule makes the outcome more explicit than an informal judgment of improvement, while the population definition identifies who is intended to contribute to the rate. The registry description says the percentage was to be estimated with a 95% exact binomial confidence interval. In general, a confidence interval conveys uncertainty around an estimate; it does not remove uncertainty or establish a causal treatment effect.

The endpoint is not a measure of how long responses last, overall survival, or comparative benefit against another treatment. Duration of remission is listed separately as a secondary outcome. The registry record does not report the primary response estimate or its confidence interval, so the endpoint definition can be described, but the observed response rate cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level outcome: objective response classified as complete or partial response, or no such response. The registry describes the result as a percentage of participants. In general, a binary rate is calculated from the number meeting the event definition relative to the relevant analysis population. The registry record does not report the event count or the resulting rate, so neither can be reconstructed from the endpoint description.

What does an exact binomial confidence interval describe?

The endpoint description specifies a 95% exact binomial confidence interval for the percentage of patients receiving drug. In general, a confidence interval gives a range of values compatible with the observed data under the stated statistical model and method. For a binary rate, the exact binomial method is based on the binomial distribution and is often used when the number of observations or events makes large-sample approximations less dependable. The interval's width reflects uncertainty in the estimated rate. It is not the probability that an individual participant will respond, and it does not establish that treatment caused an outcome.

No response estimate or interval limits are reported in the registry record. Therefore, the width, location, and practical interpretation of the planned interval cannot be assessed. The confidence interval method should be understood as part of the analysis description, not as evidence that an analysis result is available.

How does the response definition affect the estimate?

The response rule uses RECIST v1.0 and requires at least a 30% decrease in the sum of the longest diameter of target lesions relative to the baseline longest diameter for an objective response. Such a threshold turns measurements into a classification used for the endpoint. The rule also means that the rate depends on the measurement process, the available baseline and follow-up assessments, and how the response categories are assigned. The record describes the rule but does not report assessment details, adjudication procedures, or the observed classifications.

The endpoint population is defined as patients with at least one post-baseline measurement. This is a population restriction tied to having a measurement after baseline. In general, excluding participants without such a measurement can affect how well the analyzed group represents all enrolled participants, particularly if missing assessments are related to health status, treatment discontinuation, or response. Those possible mechanisms cannot be determined from this record. The registry does not report a missing-data method or explain the gap between enrollment and the evaluable population.

What can a single-group design estimate?

A single-group study can describe outcomes observed in its participants. It cannot by itself distinguish a treatment effect from other explanations for those outcomes, because no concurrent control group is listed. Non-random allocation also means that there is no randomized assignment process for balancing factors between treatment groups. In this study there is one group, so the central statistical quantity would be a response proportion, not a between-arm treatment difference.

In general, randomization supports causal comparison by making treatment assignment independent of participant characteristics in expectation. A single-arm estimate does not have that feature. The record includes no comparator response rate or external benchmark for a formal comparison, and none should be inferred from the endpoint definition.

What do the safety counts represent?

The safety listing reports groups for thymoma and thymic carcinoma, with counts at risk and counts affected for serious and other adverse events. These are descriptive counts as recorded. The selected serious-event terms have percentages attached, but the record does not provide enough detail to infer a rate over person-time or determine whether a participant could contribute more than one event term. In general, adverse-event counts and percentages need their definitions, denominator, observation period, and event-collection rules for full interpretation.

The registry record does not report a statistical comparison of safety between the diagnosis groups. The two groups should not be treated as randomized arms, and the counts do not establish that diagnosis caused a difference in event occurrence. Death counts are not reported in the registry record.

What analysis details are absent?

The record lists 0 analyses. It does not report a statistical analysis plan, sample-size justification, interim analyses, or a procedure for handling missing primary endpoint data. The exact interval method is stated in the endpoint description, but further analytic choices are not described. In general, these details matter because analysis populations, missing outcomes, response assessment timing, and multiplicity handling can affect interpretation. Their absence does not prove that no such procedures existed; it means they are not reported in the registry record.

The record's completion status and timeline do not substitute for those missing analytic details. Nor do they make it possible to calculate a response estimate. The defensible statistical reading is limited to the design, outcome definitions, population description, and safety counts that are actually recorded.

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("Thymoma", "Thymic Carcinoma")
n      <- c(15, 11)
events <- c(4, 1)
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  Thymoma  15  4  26.7  7.8  55.1  10.9  52.0  11.0  52.4
ARM  Thymic Carcinoma  11  1  9.1  0.2  41.3  1.6  37.7  2.1  38.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures: the primary objective response endpoint and secondary outcomes that include duration of remission and Grade 3/4 treatment-related adverse events. It does not describe how multiple outcomes were handled statistically. A multiplicity procedure, if any, is not reported in the registry record. In general, when several outcomes or repeated statistical tests are considered, the chance of a nominally positive finding can change; the record does not support a claim about whether adjustment was planned or used.

The record lists 0 analyses and provides no primary response estimate or confidence interval. It also does not report analyses for the secondary outcomes. Therefore, multiplicity cannot be evaluated from the posted information, and no conclusion about statistical significance or prespecified testing hierarchy is available.

The endpoint population is defined as participants with at least one post-baseline measurement. It is described as 26 evaluable participants, including 15 with thymoma and 11 with thymic carcinoma, while enrollment is listed as 27. The reason for this difference is not reported in the registry record. The record does not describe whether missing outcome measurements were imputed, treated as nonresponse, or handled by another approach. It also does not give a disposition for participants without post-baseline measurements.

In general, missing data can affect a rate estimate if the participants with missing measurements differ from those assessed. Without the number and reasons for missing assessments or a stated analysis rule, the direction and size of any effect cannot be determined. The described evaluable population should not be assumed to be identical to every possible analysis population, and the registry provides no further population definitions.

A sample-size justification and interim-analysis plan are not reported in the registry record. That absence means the planned precision, stopping considerations, and intended control of repeated looks cannot be assessed. It does not establish what investigators did outside the information entered in the record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: superior vena cava syndrome (svc) (9.1%), abdominal pain (9.1%), fever (9.1%), blood infection (staphlococcus hominis) (9.1%), pneumonitis (9.1%).

The safety listing separates participants with thymoma from those with thymic carcinoma. For thymoma, the record reports 16 at risk and 2 affected for serious adverse events; for thymic carcinoma, it reports 11 at risk and 3 affected. These are the counts as recorded, not a comparison between randomized groups. The record also reports 16 at risk and 16 affected for other adverse events in the thymoma group, and 11 at risk and 11 affected in the thymic carcinoma group.

The selected serious adverse-event terms include superior vena cava syndrome (SVC), abdominal pain, fever, blood infection (Staphylococcus hominis), pneumonitis, and dyspnea. The record attaches percentages to those terms, including 9.1% for each of the first five listed terms and 6.2% for dyspnea. These are registry-reported percentages; the record does not explain the denominator or whether event terms can overlap within a participant. They should not be added or read as mutually exclusive categories.

In general, adverse-event counts describe reported events within the specified recording framework. They do not alone establish causation, severity for every individual, or comparative safety against another treatment. Death counts are not reported in the registry record. The record also does not provide a detailed safety analysis or the duration of observation underlying these listings.

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

The registry record establishes that a Phase II, single-group study of pemetrexed in advanced thymoma and thymic carcinoma was completed and that objective response was the primary endpoint. It describes the response definition, the evaluable population, the planned confidence interval method, and selected safety information. These details make the intended statistical question identifiable, but they do not supply the primary endpoint result.

The key efficacy information needed to interpret the study is not reported in the registry record: the number of participants with a complete or partial response, the estimated response percentage, and the confidence interval limits. Without those values, the observed response magnitude and precision cannot be described. The fact that the endpoint was planned, or that the record is marked completed, is not a substitute for an outcome analysis.

Even if a response percentage were available, the single-group, non-randomized design would support a description of outcomes in this study population rather than a randomized causal comparison. There is no concurrent control group listed. The study therefore cannot, on its design alone, establish how outcomes would compare under another treatment or without pemetrexed.

The safety counts offer some descriptive information by diagnosis group, and selected serious event terms have recorded percentages. They do not provide a complete comparative safety assessment. The record does not report deaths, detailed event timing, participant-level overlap, or a statistical safety comparison. Duration of remission is listed as a secondary outcome, but its analysis is not reported.

The record also leaves important analysis questions unanswered, including the handling of missing endpoint measurements, the reason the endpoint population differs from enrollment, multiplicity procedures, sample-size justification, and interim analyses. These omissions limit assessment of precision, representativeness, and the analysis plan. They do not prove that methods were absent in practice; they indicate that the methods are not reported in the registry record.

Accordingly, the available information supports a description of study design and endpoint intent, not a conclusion about the size or certainty of the observed response, nor a claim that pemetrexed does or does not work. Those judgments require reported efficacy analyses and, for comparative claims, a suitable comparator design.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a clearly specified endpoint and a reported result. The registry defines objective response using RECIST v1.0, gives a threshold based on change from baseline, identifies a population with post-baseline measurement, and names an exact binomial confidence interval. Those details outline how an efficacy estimate was intended to be framed.

At the same time, the record lists 0 analyses and does not report the primary response estimate or interval. This gap matters because an endpoint definition cannot convey the observed event frequency or its uncertainty. Readers need both the estimate and a measure of precision to judge what the study data support. Without them, quantitative interpretation of efficacy is not possible from the registry record.

The single-group design also makes the scope of any potential inference important. A rate in one treated cohort is descriptive; it is not a randomized treatment contrast. This distinction is central in clinical research because an observed outcome proportion does not isolate the effect of treatment from other influences. The study's title and completed status do not change that design limitation.

The record also illustrates why analysis populations and safety denominators matter. Enrollment is 27, while the primary endpoint description identifies 26 evaluable participants. The reason for the difference is not reported. Safety is listed separately by diagnosis group, and the event percentages are not accompanied by an explanation of denominator or overlap. These are interpretive considerations, not grounds for inventing missing counts or analyses.

Finally, the record names secondary outcomes but does not report their analyses or explain multiplicity, missing-data, or sample-size procedures. The distinction between what was planned and what was reported is therefore essential. The study can be described statistically in terms of its design and measures, while the efficacy result remains unavailable 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.

A central limitation is that the registry record does not report the primary objective response estimate, its exact binomial confidence interval, or the analyses for the listed secondary outcomes. Although the endpoint method and response definition are described, the result and its precision cannot be assessed.

The study is non-randomized and single-group, with no concurrent comparator listed. This limits inference to description of outcomes in the study cohort and does not permit a randomized comparison. The registry record does not identify an external control or benchmark for comparison.

The endpoint population is defined by having at least one post-baseline measurement and is described as 26 evaluable participants, while enrollment is 27. The reason for this difference, the disposition of participants, and any missing-data handling are not reported in the registry record. That leaves uncertainty about how the endpoint population relates to everyone enrolled.

The record does not report the response assessment process beyond the RECIST v1.0 definition, nor does it provide further information on assessment timing, review, or adjudication. Although the timeframe is listed as up to 3 years, follow-up duration for individual participants is not reported in the registry record.

Safety information is limited to group counts and selected serious-event terms with percentages. The record does not state the denominator basis for those percentages, whether event terms overlap, or the safety observation period. Death counts are not reported. The record also does not report a sample-size justification, interim-analysis plan, multiplicity procedure, or detailed statistical analysis plan. These omissions limit evaluation of precision and analytic choices; they should not be taken as evidence that a particular procedure was or was not used outside the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Study of Alimta (Pemetrexed) Treatment of Advanced Thymoma and Thymic Carcinoma — NCT00198133.
• Registry record last updated 2019-07-22; status last verified 2019-07.
• Results first posted 2016-01-25.
• 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, non-randomized, single-group study of pemetrexed in advanced thymoma and thymic carcinoma. Enrollment is listed as 27. The primary endpoint was objective response, defined as complete or partial response under RECIST v1.0, among patients with at least one post-baseline measurement. The endpoint population is described as 26 evaluable participants, comprising 15 with thymoma and 11 with thymic carcinoma.

The planned endpoint estimate was a percentage with a 95% exact binomial confidence interval, and the timeframe was up to 3 years. The response result and interval are not reported in the registry record. Duration of remission and Grade 3/4 treatment-related adverse events are listed as secondary outcomes, but their analyses are not reported. Safety counts and selected serious-event terms are recorded; death counts are not reported. The reason for the difference between enrollment and the evaluable population, and the missing-data and multiplicity approaches, are not reported in the registry record.