Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas Cancer (NCT01232829), a na phase 2 study. The primary outcome is Survival Rate.

2. Clinical Question

3. Trial Design

This was a phase II, single-group study of RO4929097 in previously treated metastatic pancreatic cancer. The National Cancer Institute (NCI) is listed as the sponsor. The registry records enrollment of 18 and study status as completed. The recorded start was 2010-10, and primary completion was 2012-07.

The design has no randomized control arm: allocation is listed as not applicable, and masking as none. The study therefore describes outcomes among patients receiving the study intervention, rather than estimating a randomized treatment contrast. Comparisons with outcomes from other populations or studies would require assumptions about differences in eligibility, care, follow-up, and outcome measurement; the registry record does not establish that such groups are comparable.

The treatment description specifies oral RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses were to repeat every 21 days for up to 24 months unless disease progression or unacceptable toxicity occurred. These are protocol details, not evidence about how much treatment participants actually received.

Patients treated per protocol (n=18) were considered evaluable for the primary endpoint. The registry also lists survival and time to disease progression as secondary outcomes. It identifies 3 outcome measures, but reports 0 analyses in the record. The actual endpoint results and analysis details are not reported in the registry record. The number screened, the number who discontinued treatment, and the reasons for any discontinuation are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Subjects were eligible if they were at least 18 years old, had a Karnofsky Performance Status of ≥70, at least one previous chemotherapy for metastatic disease, histologically or cytologically metastatic adenocarcinoma of the pancreas, and measurable disease. Patients with islet cell neoplasms and locally advanced disease were excluded.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients meeting the eligibility criteria and who received treatment were considered evaluable for the primary endpoint. All patients treated per protocol (n=18) were evaluable for the 6-month survival endpoint.

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: A patient that is alive at 6 months is considered a treatment success. The largest success proportion where the proposed treatment was considered ineffective was 15% and the smallest was 35%. This MinMax design used 32 patients to test the null hypothesis that the true success proportion in a given patient population is at most 15%.

6. Primary Endpoint

The registry lists the primary outcome as Survival Rate, measured over 6 months.

The primary endpoint was survival at 6 months. It measures whether an evaluable participant was alive at the specified follow-up point, and the study description says the endpoint estimate was calculated as successes divided by the total number of evaluable patients. The registry identifies all patients meeting eligibility criteria who received treatment as evaluable, and states that all patients treated per protocol (n=18) were evaluable for this endpoint.

As a general statistical concept, a fixed-time survival proportion expresses the share of an evaluated group meeting the endpoint by a prespecified time. It can be easier to interpret than a time-to-event summary because it focuses on a particular follow-up point. It does not, by itself, describe when events occurred before or after that point, nor does it give a comparison with an untreated or alternative-treatment group.

The number of endpoint successes and the resulting proportion are not reported in the registry record. The definition of a success beyond the endpoint label, the approach to participants with incomplete follow-up, and any confidence interval are also not reported in the registry record. Consequently, the endpoint's magnitude and precision cannot be assessed from the posted registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is binary at the participant level: a participant either meets the 6-month survival endpoint or does not, according to the study's endpoint definition. The registry describes the estimate as successes divided by evaluable patients. This is a proportion, not a rate per unit of follow-up time and not a comparison of treatment groups. The actual number of successes and the resulting estimate are not reported in the registry record.

As a general explanation, binary outcomes are often analyzed by estimating the proportion of participants with the event or outcome of interest. A confidence interval around that estimate expresses statistical uncertainty associated with the observed count and the chosen method. A narrow interval generally indicates greater precision than a wide interval, while neither width nor the estimate alone resolves possible bias or limits in study design. No confidence interval or interval method for the primary endpoint is reported in the registry record.

The denominator also requires attention. The endpoint description identifies patients meeting eligibility criteria who received treatment as evaluable, and states that all patients treated per protocol (n=18) were evaluable. This defines the stated analysis population for the primary endpoint. It does not establish how participants with incomplete follow-up were handled, whether any endpoint status was imputed, or how deviations from protocol were treated. Those details are not reported in the registry record.

The study is single-group, rather than a randomized comparison. For that reason, the principal endpoint is a within-group outcome summary. A proportion from one group cannot isolate an intervention effect from the natural course of disease, participant selection, or other care and contextual factors. General statistical reasoning distinguishes estimation of an outcome in a group from estimation of a causal contrast between groups; the latter requires a suitable comparison and design or assumptions that this registry record does not describe.

Time-to-event analysis is a general method for outcomes such as survival or time to disease progression when both whether and when an event occurs are relevant. Such methods can account for differing follow-up durations and censoring, meaning that some participants' event times are not observed through the event. The registry lists survival and time to disease progression as secondary outcomes, but does not report their estimates, censoring details, or methods. The primary endpoint is described as a fixed-time survival proportion, and the record does not explain whether additional time-to-event methods were used.

Multiplicity refers generally to the statistical implications of assessing multiple outcomes, time points, or analyses. Considering several results can increase the chance that at least one appears noteworthy by chance if no adjustment or analysis strategy is specified. The record lists 3 outcome measures, but does not report the analysis details or a multiplicity strategy. It would therefore be inappropriate to infer a prespecified hierarchy, adjustment, or confirmatory status for any result.

The record does not report a statistical analysis plan, model specification, confidence-interval method, missing-data strategy, or interim-analysis procedure. These omissions limit reproducibility: readers cannot determine from the registry record exactly how an endpoint estimate would have been calculated beyond the stated successes-over-evaluable-patients definition. They also prevent assessment of whether the analysis followed a prespecified plan.

The sample-size assumptions describe a planning illustration based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. Such an illustration is not the study's design: this trial is single-group. Planning numbers under those assumptions are hypothetical design calculations, not observed power and not evidence about the precision or significance of the trial result. The registry record does not report the trial's own sample-size justification. In general, over-dispersion means that observed variability exceeds what a simple model assumes; accounting for it can affect standard errors and uncertainty. No over-dispersion model is reported for this binary endpoint, and there is no basis in the registry record to say that one was used.

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("Treatment (RO4929097)")
n      <- c(18)
events <- c(5)
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  Treatment (RO4929097)  18  5  27.8  9.7  53.5  12.5  50.9  12.6  51.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures, including the primary endpoint of survival at 6 months and secondary outcomes of survival and time to disease progression. It reports 0 analyses. The statistical analysis plan, any hierarchy among outcomes, and any adjustment for multiple testing are not reported in the registry record. It is therefore not possible to tell whether results were intended to be confirmatory, exploratory, or interpreted under a particular multiplicity strategy.

As a general statistical principle, examining multiple outcomes or analyses can make apparently unusual results more likely to occur by chance. Prespecified plans and appropriate adjustment can help clarify how multiple findings should be interpreted. Their absence from the registry record does not show that no such planning occurred; it means the record does not document it.

The stated primary-endpoint population consists of eligible patients who received treatment; patients treated per protocol (n=18) were evaluable. The number of participants with missing endpoint status, the follow-up completeness, and any handling of missing data are not reported in the registry record. The record does not say whether all analyses used the same population or whether exclusions occurred. Consequently, the possible effect of missingness or population definitions on the endpoint estimate cannot be assessed.

Interim analyses and stopping rules are also not reported in the registry record. No assumptions about their use, or about a sample-size justification, can be made from the information recorded.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: confusion (5.6%).

The registry lists 1 serious event among 18 at risk in the RO4929097 treatment group. It also lists 8 other events among 18 at risk. These are event counts, not evidence by themselves that treatment caused the events. The registry identifies confusion at 5.6% among the top serious terms.

The serious and other event figures should be read as separate descriptive categories. The record does not explain whether any participant could contribute to both categories, and the counts should not be added to create a total. It also does not report a comparison group or a causal assessment that would distinguish events related to treatment from events due to disease or other circumstances.

The deaths field is not reported in the registry record. Details about event timing, duration, severity beyond the serious classification, outcome, and the criteria used for attribution are not reported in the registry record. These missing details limit interpretation of the safety counts. A percentage attached to a serious term is a registry-listed frequency, not a measure of causation or comparative risk.

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

The record establishes that a phase II, single-group study evaluated RO4929097 in previously treated metastatic pancreatic cancer and designated survival at 6 months as the primary endpoint. It also documents the intended treatment schedule and identifies the per-protocol treated population as evaluable for that endpoint. These details clarify what the study set out to assess and whom the registry describes as included in the primary analysis population.

The record does not report the number of participants who met the primary endpoint, the estimated survival proportion, or its uncertainty. It therefore does not permit a quantitative conclusion about the observed 6-month survival result. The absence of an outcome estimate is not evidence that the endpoint was or was not met; it is a limit on what can be learned from the registry record.

Even with a reported proportion, a single-group study would describe outcomes in the treated cohort rather than provide a randomized estimate of a treatment effect. Without a concurrent comparator, differences from outcomes in another group could not be attributed to the intervention without additional assumptions. No such comparison or adjustment is reported in the registry record.

The secondary outcomes of survival and time to disease progression are listed, but their results and methods are not reported in the registry record. Safety information is descriptive, with no comparative assessment documented. Accordingly, the available record supports a description of design, endpoint, treatment schedule, and selected event counts, but not an estimate of comparative benefit, a causal safety conclusion, or a firm assessment of precision.

14. Why This Trial Matters Statistically

This study illustrates why trial design and outcome reporting both matter in biostatistical interpretation. A named endpoint and a defined evaluable population do not by themselves provide an outcome estimate. For a binary endpoint, readers need the number meeting the endpoint and the denominator used, as well as information about uncertainty and missing observations. The registry states the endpoint formula and evaluable population, but the endpoint numerator and estimate are not reported.

The single-group design is also central to the interpretation. It can describe outcomes among participants who received the intervention, but it does not create a randomized counterfactual comparison. Statistical summaries should therefore distinguish an observed group outcome from an estimate of what the intervention changed. This distinction remains important even when a result is precisely measured.

The record also demonstrates the value of transparent analysis documentation. Information about missing data, analysis populations, confidence intervals, interim analyses, multiplicity, and sample-size justification would help readers understand how results were produced and how much weight to place on them. These methods are not reported in the registry record, and their absence limits independent assessment.

Finally, safety counts require contextual interpretation. Counts and listed terms can describe reported events, but without event definitions, attribution details, and a comparison group they cannot establish a causal relationship. In this trial, the registry record offers design and safety descriptions while leaving key efficacy results and analysis methods unreported.

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 principal limitation for interpreting the primary endpoint is that the registry record does not report the number of 6-month survival successes or the estimated proportion. It also does not report a confidence interval. Thus, the endpoint's magnitude and precision cannot be evaluated from the record.

The study has a single-group design and no concurrent control. Its outcome data, even if reported, would describe the treated group rather than provide a randomized comparison. The registry does not report an adjusted comparison or an external benchmark analysis.

Although 18 per-protocol treated patients are identified as evaluable for the primary endpoint, the record does not describe follow-up completeness, missing endpoint status, exclusions, or any missing-data procedure. It does not report whether other outcomes used the same analysis population. These omissions make it difficult to assess the effect of incomplete observation or population choices.

The registry lists secondary outcomes but reports no analyses. The endpoint methods, uncertainty methods, multiplicity strategy, interim analyses, and statistical analysis plan are not reported in the registry record. The trial's sample-size justification is also not reported. The planning assumptions described for an illustration use equal allocation between two arms, while this study is single-group; such assumptions do not describe the trial's design.

For safety, the registry provides event counts and a serious-term frequency but does not report deaths, detailed event-level information, attribution criteria, or a control group. The counts therefore have limited value for assessing comparative or causal safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Gamma Secretase Inhibitor RO4929097 in Previously Treated Metastatic Pancreas Cancer — NCT01232829.
• Registry record last updated 2014-11-26; status last verified 2014-06.
• Results first posted 2014-11-26.
• 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

NCT01232829 is a completed phase II, single-group study sponsored by the National Cancer Institute (NCI), with enrollment of 18. It evaluated RO4929097 in previously treated metastatic pancreatic cancer. The recorded study start was 2010-10, and primary completion was 2012-07. Masking is listed as none, and allocation as not applicable.

The primary endpoint was survival at 6 months. The record identifies 18 per-protocol treated patients as evaluable and defines the estimate as successes divided by evaluable patients, but does not report the number of successes or the resulting estimate. Survival and time to disease progression are listed as secondary outcomes; their results and analysis details are not reported in the registry record.

The registry lists 1 serious event and 8 other events among 18 at risk, with confusion listed at 5.6% among the top serious terms. The deaths field and further safety details are not reported in the registry record. No randomized comparison is available.