Pemetrexed Plus Gemcitabine in Renal Cell Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pemetrexed Plus Gemcitabine in Renal Cell Cancer (NCT00491075), a na phase 2 study. The primary outcome is Overall Response.

2. Clinical Question

In practical terms, the registered question concerns whether participants in this single group met criteria for complete or partial response after receiving the combination. Because no control group was included, the trial was not designed to estimate a treatment effect relative to another regimen or to no treatment. Its stated secondary objectives were toxicity and estimation of survival rate. The record lists a safety summary, but does not report a survival result or an analysis of progression-free survival. Thus, the intended clinical questions are broader than the results that can be read from the available registry record.

3. Trial Design

This was a Phase II, single-group study sponsored by M.D. Anderson Cancer Center. The registry lists the condition as renal cell carcinoma and the official title specifies advanced non-clear cell renal cell cancer. The study began in 2005-12, reached primary completion in 2011-09, and is listed as terminated. Enrollment was 16 participants.

The trial model is single group, allocation is NA, and masking is none. These entries describe an unmasked study without an allocation between competing trial arms. The only described arm is Pemetrexed + Gemcitabine. It received pemetrexed 500 mg/m^2 intravenous (IV) and gemcitabine 1500 mg/m^2 IV on Day 1. The registry record does not state how often that Day 1 administration was repeated, the planned number of cycles, or additional treatment-management details.

The primary objective was to assess clinical activity, with response rate and progression-free survival named in the objective. Toxicity and survival rate were listed as secondary objectives. The one registered primary outcome measure is Overall Response, expressed as a percentage of participants, with a 95% confidence interval listed as the dispersion measure. Its timeframe text includes baseline to 8 weeks (after 4 cycles) and protocol response at 16 weeks. The registry record does not clarify the relationship between those timing statements.

The record reports that one participant did not meet the required 16-week data endpoint and was excluded from response evaluation and analysis. It does not report the overall-response estimate, its confidence interval, or a statistical analysis. A control group, randomization, masking, and comparative treatment estimate are not part of the recorded design. These features limit interpretation to a description of the treated group and do not support a controlled estimate of the combination’s 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: One participant did not meet the required 16 week data end point and was excluded from the response evaluation and analysis.

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 Overall Response, measured over Baseline to 8 weeks (after 4 cycles) protocol response at 16 weeks.

The primary endpoint, Overall Response, counts participants whose best response met the registry’s definition of complete response or partial response. It is described as a percentage of participants, with a 95% confidence interval as the intended measure of precision. The response criteria are based on RECIST. Complete response is described as disappearance of all target lesions. Partial response requires a decrease of more than 30% in the sum of the longest diameters of target lesions, relative to the baseline sum. The registry also describes progressive disease using an increase of more than 20% relative to the smallest sum recorded since treatment started, or the appearance of new lesions. Stable disease is the category that meets neither the partial-response nor progressive-disease criteria.

A response endpoint provides a categorical summary of tumor change over the stated assessment period. Combining complete and partial responses into one endpoint makes the outcome the proportion meeting either response definition, rather than a measure of the size or duration of each participant’s change. The stated timeframe refers to baseline to 8 weeks after 4 cycles and also mentions protocol response at 16 weeks. The registry record does not clarify how these time references fit together or give details of response confirmation or assessment procedures beyond the RECIST description.

The record says one participant did not meet the required 16-week data endpoint and was excluded from response evaluation and analysis. It does not report how many of the evaluated participants had complete or partial response, the resulting percentage, or the confidence interval. Therefore, the endpoint definition is available, but the response result cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins by distinguishing an endpoint definition from an endpoint result. The record defines Overall Response as the number of participants meeting complete- or partial-response criteria and expresses it as a percentage of participants. It also names a 95% confidence interval as the intended measure of dispersion. However, the numerical response count, percentage, and interval are not reported in the registry record. The endpoint can therefore be explained, but no estimate can be evaluated for size or precision.

What does a response percentage represent?

General statistical explanation: a response percentage is a proportion. Its numerator is the count of participants who satisfy the response definition, and its denominator is the set of participants included in the response evaluation. In this trial, the response definition combines complete and partial response under RECIST. The registry states that one participant did not meet the required 16-week data endpoint and was excluded from response evaluation and analysis. It does not report the actual response numerator or explicitly give the analysis denominator. The safety population count should not be substituted for the response denominator unless the analysis population is documented as the same.

A proportion compresses a set of categorical outcomes into one number. That can make the endpoint easy to communicate, but it does not show the range of tumor changes, the time to response, how long a response lasted, or what happened to each participant. Those details require other outcomes or participant-level reporting. The registry’s primary endpoint is not a continuous measure of tumor size and does not itself convey progression-free survival.

How should a confidence interval be understood?

General statistical explanation: a confidence interval describes uncertainty around an estimate under the statistical method used to calculate it. It is not a guarantee that the true value lies within the interval, and it does not establish that a result is clinically important. An interval’s width depends on factors including the amount of information and the variability in the data. In a small study, estimates may be imprecise, but the actual interval is needed to assess that imprecision. Here, a 95% confidence interval is listed as the endpoint’s dispersion measure, but its bounds are not reported in the registry record. No interval width or confidence-limit interpretation can therefore be made.

General statistical explanation: the confidence level does not by itself determine the analysis method. Different methods for proportions can yield different limits, especially when counts are small or a proportion is near a boundary. The registry record does not name the interval calculation method. It would be inappropriate to infer which method was used or to construct replacement limits from information that is not reported.

What does the single-group design allow?

General statistical explanation: in a single-group study, the observed outcome describes participants who received the study intervention. A comparator group is needed for a direct between-group contrast. In its absence, there is no randomized trial estimate of the difference in response between the combination and another treatment or control condition. A response result, if available, would still be informative as a description of this group, but it would not by itself identify the causal effect of treatment. This limitation follows from the design, not from the response endpoint’s calculation.

The trial is unmasked and has allocation listed as NA. The record does not describe a blinded outcome assessment or other measures intended to limit assessment bias. RECIST supplies stated criteria for classifying response, but standardized criteria do not establish that assessments were blinded, independently reviewed, or performed at a particular schedule. Those details are not reported in the registry record.

Why do denominators and missing observations matter?

General statistical explanation: a proportion is interpretable only when its denominator and handling of missing outcomes are clear. Excluding participants without endpoint data can change the group represented by the estimate, particularly if the reasons for missing data relate to health status or response. Counting every enrolled participant as a non-responder is a different analytic choice from excluding participants without evaluable assessments; the two choices can yield different estimates. The record explicitly says one participant was excluded from response evaluation because the required 16-week data endpoint was not met. It does not state whether alternative missing-data approaches were planned or performed.

The record lists 16 enrolled participants and one exclusion from response evaluation. These registry entries do not supply an observed response estimate. Nor do they establish why the data endpoint was not met, whether the participant received the full intended treatment, or what outcome the participant might have had. Such information is not reported in the registry record. The safest interpretation is to keep enrollment, endpoint evaluability, and safety assessment distinct.

What can sample-size planning tell readers?

General statistical explanation: sample-size planning uses assumptions about the outcome, target effect, variability, significance level, and desired power to guide a future study’s design. A planning calculation is not an observed result, and power calculated after a trial from its observed effect is not a measure of the probability that the finding is true. The registry record does not report the trial’s own sample-size justification or planning assumptions. Any planning illustration associated with a displayed effect should be read as a hypothetical design scenario, not as evidence about this trial’s outcome or as observed power.

The trial is single group, while a planning illustration described in the record’s statistical material assumes equal allocation between two arms and a two-sided significance level of 0.05. Those assumptions do not describe the observed trial design. The record does not provide numerical planning outputs in the registry record for interpretation here, and no new calculation can establish them. A hypothetical two-arm calculation also cannot serve as a substitute for an analysis of this single-group study.

Finally, the registry record does not report an inferential analysis, a statistical analysis plan, interim analyses, or a method for multiplicity adjustment. Their absence from the record should not be treated as proof that no such work occurred; it means their details are not reported in the registry record. The result available for statistical interpretation is therefore limited to the design, outcome definition, stated exclusion, and safety counts—not a reported estimate of efficacy.

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("Pemetrexed + Gemcitabine")
n      <- c(14)
events <- c(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  Pemetrexed + Gemcitabine  14  1  7.1  0.2  33.9  1.3  31.5  1.7  31.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure, Overall Response, and states that clinical activity was to take into account response rate and progression-free survival. Toxicity and survival rate were secondary objectives. This creates several distinct questions, but the record does not describe a hierarchy of hypotheses, a multiplicity adjustment, or a plan for interpreting multiple outcomes together. Whether any formal adjustment was made is not reported in the registry record.

Multiplicity matters in general because examining several outcomes or analyses can increase the chance of at least one apparently notable finding when each is interpreted separately. The record does not provide enough information to determine whether this issue was addressed in the trial’s analysis. It also reports no statistical analyses, and no progression-free-survival or survival result.

For missing endpoint data, the record identifies one participant who did not meet the required 16-week data endpoint and was excluded from response evaluation and analysis. The reason the data endpoint was not met, the participant’s clinical outcome, and any sensitivity analysis for missing data are not reported in the registry record. No intention-to-treat, per-protocol, or other named analysis population is specified in the record. The enrollment count and safety counts should not be used to infer an unreported response analysis denominator.

These omissions matter because the result can depend on who is included and how missing outcomes are handled. General statistical explanation: excluding participants with missing assessments relies on assumptions about those missing observations; treating missing outcomes as non-response makes a different assumption. Neither approach can be attributed to this study beyond the explicit exclusion described in the registry record. The stated exclusion should be reported plainly, without imputing an outcome or assuming that the participant’s missing assessment reflects either response or lack of response.

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: thromboembolic event (6.7%).

The safety summary lists the Pemetrexed + Gemcitabine group with 15 participants at risk for serious adverse events and 1 participant affected. For other adverse events, it lists 15 participants at risk and 15 affected. The registry also identifies thromboembolic event as a top serious term, with 6.7%. These figures are the safety information reported in the registry record; they do not replace a detailed account of event types, timing, severity, or clinical course.

The at-risk count describes the participants included in the relevant safety summary, while the affected count describes participants reported as affected in that category. These counts should not be confused with the number of individual events, since a participant may experience more than one event. The record does not define the collection period or provide further detail about how events were coded or attributed. The serious adverse event count and the broader other-adverse-event count are separate categories in the summary, and should not be added together.

The 6.7% value is reported for the thromboembolic event term. The registry record does not provide additional event-level context alongside that percentage. Deaths are listed as null, which means a death count is not reported in the registry record; it should not be interpreted as zero. Safety findings are descriptive in a single group and do not establish comparative risk relative to a control.

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

The registry record provides a defined response outcome and some safety counts for a single-group Phase II study of pemetrexed plus gemcitabine in advanced non-clear cell renal cell cancer. It does not report the primary response result. Without the number of participants meeting response criteria, the response percentage, or the stated 95% confidence interval, the size and precision of the observed response cannot be assessed from the record.

That missing result does not establish that there were no responses, nor does it establish that there were responses. It means the registry record does not report the result needed to answer the registered primary outcome question. The fact that the study enrolled 16 participants and that one participant was excluded from response evaluation does not allow the response count to be reconstructed. Safety counts are not a substitute for the efficacy endpoint.

Even if a response percentage were available, the single-group design would make it a description of outcomes among treated participants rather than a randomized comparison. It would not show whether outcomes differ from those under another treatment or from what might otherwise have occurred. The record also does not provide the progression-free-survival or survival findings named in the objectives, so those objectives cannot be treated as results.

The safety summary reports one participant affected in the serious adverse event category among 15 at risk, and 15 affected among 15 at risk for other adverse events. It also reports thromboembolic event at 6.7% among top serious terms. These data provide limited descriptive information, but the registry record does not provide event-level detail or a comparator. The null entry for deaths is not a reported zero.

The trial’s terminated status gives its registry status, not a reason for termination or an explanation of the absent efficacy analysis. The reason is not reported in the registry record. Overall, the record supports an account of the study’s design, endpoint definition, one exclusion, and reported safety counts. It does not support a conclusion about the magnitude, precision, or comparative effect of the treatment on response, progression-free survival, or survival.

14. Why This Trial Matters Statistically

This trial illustrates why a registry entry should be read as a record of both design and available results, rather than as a complete report of every objective. The study had a stated clinical-activity objective and a defined RECIST response endpoint, but the registry record does not report the endpoint’s numerical result or its confidence interval. An outcome definition alone is not evidence about the observed outcome.

The case also highlights the importance of distinguishing enrollment from evaluability. Sixteen participants were enrolled, while the record states that one participant did not meet the required 16-week data endpoint and was excluded from response evaluation and analysis. A reader needs a clear analysis denominator and transparent missing-data handling to interpret a response proportion. The registry does not provide a numerical response estimate or further analysis details.

Design determines what questions the data can answer. A single-group, unmasked study can describe outcomes in the participants who received the combination, but it does not provide a randomized comparator for estimating a treatment contrast. That distinction remains important even when the endpoint uses standardized response criteria and the safety summary supplies counts.

Finally, secondary objectives and safety listings should not be mistaken for full outcome reporting. The objectives name toxicity and survival, while the safety summary gives limited counts and no survival result is reported. The terminated status does not explain why the study ended or why outcome analyses are absent. These features make this record a useful example of how missing results, an explicitly excluded participant, and a non-comparative design constrain 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.

Several trial-specific limitations constrain interpretation. First, the registry record does not report the overall-response count, percentage, or 95% confidence interval, despite listing Overall Response as the primary outcome. It also does not report a progression-free-survival analysis or survival result, although these outcomes appear in the objectives. The efficacy questions therefore cannot be answered from the posted results.

Second, response evaluation excluded one participant who did not meet the required 16-week data endpoint. The reason the endpoint data were not available and the participant’s outcome are not reported in the registry record. The record does not name the response analysis population, provide further missing-data handling details, or report a sensitivity analysis.

Third, the single-group, unmasked design has no control arm. It cannot provide a direct randomized comparison, and the record does not describe blinded response assessment or independent review. The registry’s RECIST descriptions identify response categories but do not supply the assessment procedures needed to evaluate possible ascertainment limitations.

Fourth, the timeframe wording for Overall Response includes baseline to 8 weeks (after 4 cycles) and protocol response at 16 weeks. The relationship between these timing references is not clarified in the registry record. The treatment description states administration on Day 1 but does not report the full dosing schedule or other treatment-management details.

Finally, the record lists the study as terminated but does not report the reason. The safety summary is limited to participant counts and a top serious-event term; additional event-level details and a reported death count are not available. These limits should be kept separate from conclusions about the treatment itself: the record’s missing outcome information does not establish a positive or negative response result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pemetrexed Plus Gemcitabine in Renal Cell Cancer — NCT00491075.
• Registry record last updated 2013-04-24; status last verified 2013-04.
• Results first posted 2012-05-03.
• 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

NCT00491075 is a Phase II, single-group, unmasked trial sponsored by M.D. Anderson Cancer Center, titled Pemetrexed Plus Gemcitabine in Renal Cell Cancer. Its official title specifies advanced non-clear cell renal cell cancer. The record lists enrollment of 16, a start date of 2005-12, primary completion in 2011-09, and status as terminated.

The described regimen is pemetrexed 500 mg/m^2 IV and gemcitabine 1500 mg/m^2 IV on Day 1. The primary outcome is Overall Response under RECIST, with a 95% confidence interval listed as the dispersion measure. One participant did not meet the required 16-week endpoint and was excluded from response evaluation and analysis. The numerical response result and statistical analysis are not reported in the registry record.

The safety summary lists 15 participants at risk and 1 affected for serious adverse events, and 15 at risk and 15 affected for other adverse events. Thromboembolic event is listed at 6.7% among top serious terms. The record does not report a survival result, the reason for termination, or a death count.