Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer (NCT01737502), a na phase 1, phase 2 study. The primary outcome is Number of Phase 1 Patients Experiencing a DLT.

2. Clinical Question

3. Trial Design

This was a phase I/II trial of auranofin combined with sirolimus in patients with advanced or recurrent non-small cell lung cancer or small cell lung cancer. The registry lists Mayo Clinic as the sponsor, records the study as completed, and gives an enrollment of 29. The recorded start date is 2014-05-14, and the primary completion date is 2023-04-24.

The design is recorded as single group, with allocation not applicable and no masking. The treatment description specifies oral auranofin on days 1-28 and oral sirolimus on days 1-28, with sirolimus omitted on days 1-7 of the first course. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The record also lists laboratory biomarker analysis and pharmacological study as interventions.

The study has a phase I and a phase II component. The primary endpoint specifically concerns phase I patients and counts participants experiencing a dose-limiting toxicity during the first 28 days. The registry says that adverse events were to be tabulated and summarized overall and by dose level. Safety information is reported for Dose Level 0 and Dose Level 1. Those groups are not randomized comparison arms, and the design does not support treating one as a controlled counterfactual for the other.

The listed secondary outcomes include overall survival time, progression-free survival time, objective response status of complete or partial response, and duration of response. The registry lists 8 outcome measures but no analyses. It does not report the rationale for the enrollment target, the planned statistical analysis, or how the phase I and phase II components were intended to contribute to decisions about treatment dosing or later evaluation.

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.

Phase I

Reasons for not completing this period:

Phase II

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Only phase 1 patients were included in 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 Number of Phase 1 Patients Experiencing a DLT, measured over 28 days.

The primary endpoint is the number of phase I patients experiencing a dose-limiting toxicity, or DLT, within 28 days. It is a participant count, not a measure of average symptom severity or time until an event. The endpoint focuses on a prespecified early treatment period and a set of adverse events considered important for evaluating tolerability during dose study.

The registry defines a DLT as an adverse event during the first cycle that is at least possibly related to study treatment and meets one of the listed severity criteria. These include grade 4 neutropenia or thrombocytopenia, anaphylaxis of grade 3 or higher, proteinuria of grade 3 or higher, hematuria of grade 3 or higher, acneiform rash of grade 3 or higher, diarrhea of grade 3 or higher, or oral mucositis of grade 3 or higher. The definition combines an attribution requirement with event type and severity.

In general, phase I studies use dose-limiting toxicity information to describe acute safety at the doses being studied. A clearly defined observation window helps specify which events count toward that endpoint. However, the registry record does not report the number of phase I participants meeting the DLT definition, nor does it report the number evaluated for this endpoint. It therefore does not permit a numerical account of the primary endpoint result or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help clarify what a study can estimate and how much confidence to place in its results. In this trial, the design and the endpoint definition are more informative than a conventional between-group effect estimate, because the registry records a single-group study and does not report a control group.

What does a participant count measure?

The primary outcome is a count of phase I participants who experienced a DLT within the first 28 days. A count answers how many people met the endpoint, but interpretation also requires knowing how many were assessed. The registry record does not report either the DLT count or the analyzed denominator. Without both, it is not possible to describe the observed proportion or its statistical precision. No denominator or rate should be inferred from the total enrollment, because the primary endpoint applies only to phase I patients.

The DLT definition specifies the observation period, treatment relationship, event types, and severity thresholds. A prespecified definition helps make classification more consistent: an event counts only if it falls within the stated window and satisfies the stated criteria. The registry says that adverse events were to be summarized overall and by dose level, but does not report the detailed analysis procedures or the primary endpoint result.

Why does the study design matter?

A single-group design describes outcomes among participants who received the study regimen. It does not directly estimate what would have happened to the same participants under a different treatment. A randomized control group can support a more balanced comparison by assigning treatment independently of participant characteristics. Here, allocation is recorded as not applicable, masking as none, and the model as single group. Dose Level 0 and Dose Level 1 are safety groupings, not a randomized controlled comparison. Differences in their observed counts can reflect factors other than dose, and the registry record does not report an adjusted comparison.

Blinding, when used, can reduce the possibility that knowledge of treatment assignment influences outcome assessment or reporting. No masking is recorded for this trial. That fact describes the design; it does not establish that assessment was biased. The registry record does not report additional procedures for limiting assessment bias.

What do uncertainty intervals and significance tests usually add?

In general, a confidence interval expresses the range of estimates compatible with the observed data under a specified statistical model. A narrower interval indicates greater precision under that model, while a wider interval indicates more uncertainty. A p-value, in general, measures how surprising data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the model assumptions held. Neither is a measure of clinical importance by itself. The registry record does not report confidence intervals, p-values, or a statistical analysis for the outcomes described in the record.

For a participant count, precision depends on the number assessed and the number with the event, as well as the method used to calculate the interval. The primary endpoint result and its denominator are not reported, so no interval can be interpreted for DLTs. The safety counts do not include confidence intervals in the registry information given for this trial. Their size and percentage descriptions should therefore be read as descriptive rather than as precise estimates of risk.

How should planning calculations be read?

General sample-size calculations are planning tools: they illustrate how much information a future study might need under stated assumptions. They are not a measure of the power achieved by a completed study. The planning assumptions associated with this record describe 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. For time-to-event outcomes, the stated calculation convention is a total number of events; other calculations are stated as participants per arm.

Those assumptions do not describe the actual single-group design as a randomized two-arm trial, and the registry does not report that they were the trial's own design assumptions. Any sample-size illustration based on an observed effect is hypothetical planning, not observed power and not evidence that a future study would reproduce that effect. The registry record does not report a sample-size justification for the trial.

What statistical issues are not resolved?

The record lists 8 outcome measures and 0 analyses. It does not describe a statistical analysis plan, a method for handling missing outcomes, or a multiplicity strategy. General concerns about multiplicity arise when several outcomes or comparisons are tested: repeated testing can increase the chance of at least one apparently unusual result. That concern cannot be quantified for this trial without the analysis plan and reported tests. Similarly, missing-data methods matter when outcome information is unavailable, but the registry record does not report the amount of missing data or how it was handled.

Overall, the available statistical information supports a careful description of the design and reported counts. It does not support re-estimating an unreported primary result, making a controlled treatment comparison, or assessing the precision of the listed safety counts.

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("Dose Level 0", "Dose Level 1")
n      <- c(3, 3)
events <- c(0, 0)
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  Dose Level 0  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Dose Level 1  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including the phase I DLT count and secondary outcomes for overall survival, progression-free survival, objective response, and duration of response. It lists 0 analyses. This means that the record available for this account does not contain outcome analysis results or a description of inferential tests. A statistical analysis plan, including any hierarchy among outcomes, is not reported in the registry record.

Multiplicity is a general concern when researchers test multiple outcomes, time points, subgroups, or comparisons. If many tests are conducted, the chance of obtaining at least one result that appears statistically notable can increase. Methods such as prespecifying a primary outcome or adjusting for multiple tests can address particular multiplicity concerns, but the registry record does not say whether such methods were planned or used. There is no basis in the record for determining how multiplicity would affect any result.

Missing-data handling is also not reported in the registry record. The record does not describe how participants with unavailable outcome information were treated, whether any outcomes were censored, or how incomplete follow-up was handled. It does not give the number analyzed for the primary endpoint. The stated primary analysis population is phase I patients, but the specific number included in that analysis is not reported. The total enrollment should not be substituted for an endpoint-specific analysis denominator. These gaps limit interpretation of the endpoint counts and prevent evaluation of whether missing information could influence the reported outcomes.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sepsis (33.3%), blood bilirubin increased (33.3%), respiratory failure (33.3%), hypotension (33.3%), bladder infection (7.7%).

The serious adverse event information is organized by dose level. Dose Level 0 reports 3 participants at risk and 2 affected by serious adverse events; Dose Level 1 reports 26 at risk and 8 affected. For other adverse events, the corresponding counts are 3 at risk and 3 affected for Dose Level 0, and 26 at risk and 23 affected for Dose Level 1. These are descriptive counts. They do not establish that the dose levels had comparable participants or follow-up, and they are not a randomized treatment comparison.

The registry lists sepsis, increased blood bilirubin, respiratory failure, and hypotension at 33.3%, and bladder infection and lung infection at 7.7%, among the serious adverse event terms. The record does not give enough context to interpret these percentages as event rates for a particular dose group or as comparative risks. It also lists 1 death for Dose Level 0 and 3 for Dose Level 1. The figures do not state whether those deaths were related to treatment.

Serious adverse events are not necessarily the same as DLTs. A DLT is defined by specific event and severity criteria, a relationship to treatment, and the first-cycle timeframe. The serious event counts do not identify which events met that definition. The DLT result itself is not reported in the registry record.

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

The registry record establishes that this completed trial evaluated auranofin with sirolimus in a single-group phase I/II study of advanced or recurrent lung cancer. It describes the treatment schedule, the phase I DLT definition, the study's listed outcomes, and safety counts by dose level. These details make it possible to understand the kind of question the study was designed to address, particularly the early toxicity question in phase I.

The record does not report the number of phase I participants experiencing a DLT. It also does not report an endpoint-specific denominator, an analysis of the primary outcome, or results for the listed secondary outcomes. As a result, the primary endpoint cannot be quantified from the registry information. The safety counts and listed serious-event percentages provide descriptive information, but without a randomized comparison they cannot show whether the regimen caused more or fewer events than another treatment.

In general, evidence about treatment effects is stronger when a study includes a suitable comparison group, clearly reported outcomes, and analyses that account for uncertainty. This trial's single-group design can document what was reported among treated participants, but it cannot by itself separate treatment effects from other explanations for observed outcomes. The dose-level counts do not resolve that limitation because the registry does not describe them as randomized comparison groups.

The results described in the registry record should not be taken as proof of benefit, lack of benefit, or a comparative safety advantage. The missing primary endpoint result, absent outcome analyses, and limited information about missing data and analysis methods prevent those interpretations. The appropriate statistical reading is narrower: the record describes a phase I/II evaluation and some safety counts, while leaving the primary DLT result and broader outcome estimates unreported.

14. Why This Trial Matters Statistically

This trial raises several important statistical issues for readers of early-phase oncology studies. Its primary endpoint is a time-bounded count of phase I participants meeting a DLT definition. That kind of endpoint is designed to characterize early safety during dose study, rather than to provide a controlled estimate of treatment benefit. Understanding the endpoint's population, observation window, event criteria, and treatment-relatedness requirement is essential before interpreting any count.

The registry record also illustrates why a reported enrollment number should not automatically be treated as the denominator for every outcome. The primary endpoint applies only to phase I patients, while enrollment refers to the study overall. Without the number assessed for the DLT endpoint, a participant count could not be translated into an event frequency even if the count were reported. Here, the DLT count itself is not reported.

Safety information by dose level may look like a comparative analysis, but the design is single group, allocation is not applicable, and there is no masking. The dose-level group counts therefore remain descriptive. This distinction matters because a comparison between groups is not automatically evidence that dose caused any difference in outcomes.

Finally, the record lists several outcomes but provides no analyses. This makes it important to distinguish planned outcomes from reported results and to avoid treating absent results as evidence of no events or no effect. The statistical value of the record lies in clarifying the design and endpoint definitions, while also showing where information needed for a fuller assessment is not reported.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report the primary DLT count or the number of phase I patients assessed for that endpoint. This prevents calculation or interpretation of an endpoint frequency and leaves the main phase I result unavailable. The overall enrollment of 29 cannot serve as the endpoint denominator because the primary endpoint analysis is restricted to phase I patients.

The design is single group, with no randomized control group. Although safety figures are listed by dose level, the registry does not describe those groups as randomized or otherwise establish that they are directly comparable. The record does not provide an adjusted comparison or enough information to attribute differences in counts to dose. No masking is recorded.

The registry lists 8 outcome measures but 0 analyses. It does not report results for the listed survival, response, or duration outcomes, or provide confidence intervals or p-values. A statistical analysis plan, multiplicity approach, sample-size justification, and missing-data methods are not reported in the registry record. The listed serious adverse event terms and percentages also lack sufficient context in this record to interpret them as dose-specific risks. Death counts are reported, but their relationship to treatment is not stated.

These limitations concern what can be concluded from the registry record; they do not establish that analyses or procedures were absent from the broader study documentation. They do mean that the record does not support a complete statistical assessment of efficacy, the primary phase I endpoint, or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer — NCT01737502.
• Registry record last updated 2025-09-05; status last verified 2024-03.
• Results first posted 2025-08-20.
• 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

NCT01737502 is a completed phase I/II, single-group trial of auranofin and sirolimus for advanced or recurrent non-small cell lung cancer or small cell lung cancer. Mayo Clinic is listed as sponsor. Enrollment was 29, with a recorded start date of 2014-05-14 and primary completion date of 2023-04-24. The primary endpoint counts phase I participants experiencing a DLT during 28 days; the registry record does not report that count. Safety information includes participant counts by Dose Level 0 and Dose Level 1, but the groups are not a randomized comparison. The record lists 8 outcome measures and 0 analyses, and does not report results for the listed secondary outcomes.