RAD001 (Everolimus) Salvage Monotherapy in Advanced Gastric Cancer (AGC) Who Failed Standard First-line Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for RAD001 (Everolimus) Salvage Monotherapy in Advanced Gastric Cancer (AGC) Who Failed Standard First-line Treatment (NCT00729482), a na phase 2 study. The primary outcome is Progression-free Survival Rate at 4-month (16 Weeks).

2. Clinical Question

3. Trial Design

This was a phase II, single-group study of RAD001 (everolimus) in patients with advanced gastric cancer that was refractory to fluoropyrimidine and platinum-based first-line chemotherapy. Asan Medical Center was the sponsor. The study is listed as completed, with an enrollment of 54 participants. Its start is recorded as 2008-07 and its primary completion as 2011-09.

All participants were assigned to the RAD001 treatment arm. Allocation is listed as not applicable, and masking is listed as none. In other words, the design did not include random assignment between treatments or masking of the treatment. The registry describes oral dosing at 10mg daily, with dose adjustment according to observed clinical toxicities. Treatment was to continue until progression or intolerance.

The stated primary endpoint was progression-free survival rate at 4 months (16 weeks). The study description says that 54 participants would be enrolled to assess the endpoint in 48 participants, assuming a dropout rate of 10%. It describes a decision framework contrasting a progression-free proportion less than or equal to 0.15 with one greater than or equal to 0.30. These statements describe the planned decision question; they do not establish how many participants were ultimately included in the endpoint analysis.

Response rate, overall survival, and the number of participants with adverse events were listed as secondary outcomes. The registry record does not report results for these outcomes, details of the analysis populations, or the statistical methods used to analyze the observed trial data. Because there was no control group, the study can describe outcomes among treated participants but cannot directly compare those outcomes with a concurrent alternative-treatment group.

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

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.

Population: Baseline analysis was based on all enrolled patients.

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival Rate at 4-month (16 Weeks), measured over 4 months (16 weeks).

The primary endpoint was the percentage of participants with progression-free survival at 4 months (16 weeks). It expresses the proportion of the study group meeting the endpoint at a specified follow-up time, rather than reporting a difference between treatment groups. The registry definition says progression was an increase of more than 20% in one or more lesions or the appearance of any new lesion.

A fixed-time progression-free rate can provide a clinically interpretable summary of disease status at a chosen point in follow-up. It focuses on whether participants have met the study’s progression definition by that time. It is distinct from a median time-to-event result, which describes the time by which an event has occurred in half of a population. The registry record does not report how participants with incomplete follow-up were handled, how progression was assessed, or how deaths were treated in defining this endpoint.

The stated decision thresholds were less than or equal to 0.15 and greater than or equal to 0.30. These thresholds indicate the proportions the study aimed to distinguish for its treatment-outcome assessment; they are not the observed result. The registry record does not report the actual 4-month proportion, an uncertainty interval, or a statistical conclusion. Thus, the endpoint’s definition and intended role are available, but its result cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a fixed-time proportion describe?

The primary endpoint is a percentage at a fixed follow-up time. In general, such a proportion describes how many participants in an analysis group meet a defined outcome by the specified time. Here, the relevant time was 4 months (16 weeks), and the registry defined progression through lesion growth or the appearance of a new lesion. A fixed-time proportion is not the same as a median time to progression: it answers a question about status at a particular time, rather than identifying a midpoint in event times.

The registry describes its aim using two values for the progression-free proportion: less than or equal to 0.15 and greater than or equal to 0.30. These express the decision question stated in the study description. They do not reveal the observed proportion, and they are not a substitute for an estimate with its uncertainty. The actual outcome and the method used to draw a conclusion from it are not reported in the registry record.

Why does uncertainty matter?

In general, a confidence interval communicates the range of estimates reasonably compatible with observed data under a specified statistical method. A point estimate alone can conceal how much uncertainty remains, particularly when the number of observations is limited. A confidence interval’s width depends on features including the amount of data and the observed proportion. No confidence interval or interval method for the primary endpoint is reported in the registry record, so the precision of any observed endpoint estimate cannot be assessed from this record.

In a single-group study, an estimate describes the participants included in that group. It does not, by itself, establish what would have happened to the same participants under another treatment. A randomized comparison can help estimate a between-group difference by assigning participants to different groups under a common study design. This study had no randomized comparator, so a relative treatment effect cannot be calculated from its design. Comparisons with results from other studies would not have the same protection against differences in populations and conduct.

What do enrollment and planned assessment counts mean?

The registry reports enrollment of 54 and states that the endpoint was to be assessed in 48 participants, assuming a dropout rate of 10%. Enrollment is the number entered in the study record; it does not establish how many had endpoint data at the specified follow-up. The planned assessment count is not an observed analysis population. The actual number assessed, reasons for missing data, and the approach to incomplete follow-up are not reported in the registry record.

Missing follow-up can affect a fixed-time proportion if participants without an assessment are handled differently from those with observed outcomes. In general, analyses may make different assumptions about participants whose endpoint status is unknown. The handling method matters because the result can depend on whether such participants are excluded, counted in a particular category, or addressed using a model. No such method is described in the registry record, so it would be inappropriate to assume one.

How should sample-size illustrations be understood?

General sample-size illustrations are planning calculations, not additional observations from a trial. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These assumptions do not describe this study’s actual design: this was a single-group trial without equal allocation between two arms. Any sample-size values generated under those assumptions should therefore be read as hypothetical planning illustrations, not as the trial’s own design justification or as evidence of observed power. The registry record does not report a sample-size justification beyond its stated enrollment and decision framework.

In general, power is a property of a planned statistical design under specified assumptions. It is not a measure of how likely a treatment is to work after observing the data. A retrospective calculation based on an observed effect does not establish the probability that the study detected a true effect. No observed primary effect is reported in the registry record, and no trial-specific power calculation or detailed statistical analysis plan is reported.

What can be inferred from the registered analyses?

The record lists four outcome measures: the primary progression-free survival rate and secondary outcomes concerning response rate, overall survival, and adverse events. It does not list analysis results. No inferential method, model, adjustment strategy, or confidence-interval method for the endpoints is reported in the registry record. General statistical explanations cannot fill in those missing study-specific details. As a result, the planned endpoint and the available enrollment information can be described, but the numerical efficacy findings and their statistical precision cannot be reconstructed from the record.

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("RAD001")
n      <- c(54)
events <- c(10)
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  RAD001  54  10  18.5  9.3  31.4  10.4  30.8  10.4  30.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes of response rate, overall survival, and adverse events. When several outcomes are assessed, interpreting multiple statistical tests can raise a multiplicity question: the chance of at least one apparently unusual result may increase when many tests are considered. General approaches can specify a primary outcome, adjust significance thresholds, or treat secondary results as exploratory. The registry record does not report whether any multiplicity strategy was planned or used.

The study description identifies the 4-month progression-free proportion as the primary endpoint and states thresholds of less than or equal to 0.15 and greater than or equal to 0.30. It does not report the statistical procedure used to evaluate those thresholds, any interim analyses, or a broader analysis plan. Those details are not reported in the registry record and should not be inferred from the endpoint description.

The registry states an intended assessment in 48 participants from an enrollment of 54, assuming a dropout rate of 10%. The number actually included in the primary analysis, the extent and reasons for missing endpoint data, and how missingness was handled are not reported. In general, incomplete follow-up can affect estimates of a fixed-time outcome, and assumptions about participants with unknown status can change the interpretation.

The analysis populations for the primary and secondary outcomes are also not reported in the registry record. It is therefore not possible to determine from the record whether the outcomes were analyzed among all enrolled participants, only those with adequate follow-up, or another defined group. The reported enrollment count should not be treated as proof that every participant contributed to every endpoint.

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: pneumonia (5.6%), ileus (1.9%), sudden death (1.9%), gastrointestinal bleeding (1.9%).

The registry lists 54 participants at risk for serious adverse events and 5 participants affected. For other adverse events, it lists 54 participants at risk and 54 affected. These are distinct summaries: the first concerns serious adverse events, while the second concerns other adverse events as categorized in the record. They should not be combined into a single count.

The listed serious adverse event terms are pneumonia at 5.6%, ileus at 1.9%, sudden death at 1.9%, and gastrointestinal bleeding at 1.9%. These percentages describe the listed terms in the registry’s safety information. They do not establish that the events were caused by the study drug, and they do not provide a comparison with a control group. The record does not give further detail about event timing, duration, management, or the number of distinct participants represented by each term.

The aggregate deaths field is not reported in the registry record. The listing of sudden death as a serious adverse event term is not a substitute for a reported aggregate deaths count. The safety summaries should be read as the available registry counts and terms, not as a complete or comparative account of risk.

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

This study was designed to assess a 4-month (16 weeks) progression-free survival rate in a single group of patients with advanced gastric cancer after failure of fluoropyrimidine and platinum-based first-line treatment. The registry sets out the endpoint definition, the intervention, and thresholds used in the stated decision question. Those design details explain what the investigators intended to assess.

The registry record does not report the observed primary endpoint result, its confidence interval, or a statistical conclusion. It also does not report response rate or overall survival results. Consequently, the record does not establish what proportion of participants was progression-free at the specified time, how precise that estimate was, or how the outcome compared with another treatment.

The single-group design is important to interpretation. An outcome rate in the RAD001 group is descriptive of that group; without a concurrent randomized comparator, it cannot establish a treatment difference. This limitation remains even if a result is considered against the study’s stated thresholds, because those thresholds do not create a control group or remove uncertainty about differences between study populations.

The safety information records serious adverse events and other adverse events among the participants at risk, with selected serious event terms and percentages. These summaries provide limited information about events recorded in the registry. They do not show comparative safety or establish cause. Further safety details and an aggregate deaths count are not reported in the registry record.

The completed status means the study is listed as completed in the registry. It does not substitute for missing outcome results. The most defensible interpretation is therefore limited: the registry describes a phase II single-group study and its planned endpoint, but does not provide the efficacy results needed to assess the observed outcome or its precision.

14. Why This Trial Matters Statistically

This trial illustrates why the design and the reported result need to be considered separately. A clearly stated endpoint can make the research question understandable, but an endpoint definition and decision thresholds do not reveal the observed outcome. For this study, the registry identifies progression-free survival at 4 months (16 weeks) and describes how progression was defined, yet does not report the endpoint estimate or its uncertainty.

The distinction between a single-group study and a controlled comparison is also central. A single group can be used to describe outcomes and to evaluate a prespecified decision question. It cannot directly estimate a difference against a concurrent alternative-treatment group. This matters when interpreting rates in a setting where the registry does not provide a comparator or comparative effect estimate.

The enrollment and planned assessment figures illustrate another statistical distinction: a target for enrollment is not necessarily the number analyzed, and an anticipated dropout assumption is not an observed missing-data pattern. Without the final analysis population and missing-data methods, readers cannot judge how much of the enrolled group contributed to the primary endpoint.

Finally, the registry’s safety summaries require attention to their scope. Serious and other adverse events are listed separately, and selected serious event terms have percentages. The record does not provide comparative safety estimates or a reported aggregate deaths count. In this case, careful statistical interpretation means identifying what the record can describe while avoiding claims that would require outcome results, uncertainty estimates, or a comparison that the registry does not report.

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 central limitation for interpreting efficacy is that the registry record does not report the observed primary endpoint result. It gives the endpoint definition and decision thresholds but no observed progression-free proportion, confidence interval, or statistical conclusion. Secondary outcome results for response rate and overall survival are also not reported in the registry record.

The study was single-group, with no randomized comparator. This limits interpretation to outcomes in the treatment group and prevents a direct estimate of comparative effects. Allocation is listed as not applicable and masking as none. The record does not report details of outcome assessment or whether any procedures were used to reduce assessment bias.

The registry reports enrollment of 54 and a plan to assess 48 participants, assuming a dropout rate of 10%, but does not report the actual primary analysis population or missing-data handling. That leaves uncertainty about how many participants contributed to the primary endpoint and how incomplete follow-up may have affected the result. The timing and methods for assessing progression are not reported beyond the stated lesion-based definition.

Further details not reported in the registry record include a trial-specific statistical analysis plan, a sample-size justification beyond the stated decision framework, interim analyses, multiplicity handling, and endpoint-specific uncertainty estimates. The adverse event information is also limited: selected terms and percentages are listed, but the record does not provide comparative safety data, detailed event descriptions, or an aggregate deaths count.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: RAD001 (Everolimus) Salvage Monotherapy in Advanced Gastric Cancer (AGC) Who Failed Standard First-line Treatment — NCT00729482.
• Registry record last updated 2020-01-07; status last verified 2020-01.
• Results first posted 2014-02-13.
• 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

NCT00729482 is a completed phase II, single-group study sponsored by Asan Medical Center. It enrolled 54 participants with advanced gastric cancer after first-line fluoropyrimidine- and platinum-based treatment. Participants received oral RAD001 (everolimus) at 10mg daily, with dose adjustment according to observed clinical toxicities.

The primary endpoint was progression-free survival rate at 4 months (16 weeks), with progression defined as an increase of more than 20% in one or more lesions or the appearance of any new lesion. Secondary outcomes included response rate, overall survival, and adverse events. The registry record does not report the primary or secondary outcome results, an analysis population, or the statistical methods for analyzing the observed data. It lists 5 participants with serious adverse events and 54 with other adverse events among 54 at risk.