Study of Arsenic Trioxide in Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Arsenic Trioxide in Small Cell Lung Cancer (NCT01470248), a na phase 2 study. The primary outcome is Response Rate (RR).

2. Clinical Question

The study also sought to examine safety and to explore whether blood or tumor-tissue biomarkers were related to tumor response. Progression-free survival and overall survival are listed as secondary outcomes, but their outcome results are not reported in the registry record. The study title identifies it as a single-arm, two-stage Phase II study; details of any stage-specific decision rules are not reported in the registry record.

3. Trial Design

The registry describes a completed Phase II study sponsored by Emory University. Its official title identifies a single-arm, two-stage design in previously treated small cell lung cancer. The allocation field is recorded as not applicable, and masking is listed as none. The model is a single group, so there is no randomized assignment between treatment arms and no blinded comparison described in the record.

Arsenic trioxide was the only listed intervention. The treatment description says all patients would receive the investigational agent according to the protocol dose and schedule. Those dose and schedule details, along with the eligibility criteria beyond the response-evaluability description, are not reported in the registry record. The brief description identifies the intended population as people who had failed at least one standard chemotherapy regimen or were unable to tolerate standard treatment.

The registry records enrollment of 20. The brief description says the study would include up to 36 participants; these are different types of registry information and should not be treated as interchangeable. The recorded start was 2011-08, primary completion was 2016-01, and the study status is completed.

Response rate was the primary outcome, assessed every 8 weeks using revised RECIST version 1.1. Progression-free survival and overall survival are named as secondary outcomes. The record also describes an interest in blood and tumor-tissue biomarkers, but biomarker findings are not reported in the registry record. Although the title calls the study two-stage, the registry record does not report the stage-specific rules, the planned statistical analysis, or any interim decision process. It therefore supports a description of the study structure, but not a reconstruction of how its design was implemented or how its results were assessed.

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: Two patients were not analyzed because only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated were considered evaluable for response.

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 Response Rate (RR), measured over Every 8 weeks.

The primary endpoint, response rate, counts participants classified as having a complete response or partial response. The registry specifies assessment every 8 weeks using the revised Response Evaluation Criteria in Solid Tumors guideline, version 1.1. Under that definition, complete response requires disappearance of all target lesions; any pathological lymph nodes must have a short axis below 10 mm. Partial response requires at least a 30% decrease in the sum of target-lesion diameters, using the baseline sum as the reference.

The criteria also define progressive disease as at least a 20% increase from the smallest sum of target-lesion diameters on study, together with an absolute increase of at least 5 mm. Stable disease is neither enough shrinkage for partial response nor enough increase for progressive disease. These categories give a standardized way to classify changes in measurable tumors; the response-rate endpoint counts only complete and partial responses, not stable disease.

Response is used in a Phase II study as a direct measure of tumor change under prespecified criteria. It does not, by itself, describe how long a response lasts or establish what would have happened without treatment. The registry says two patients were not analyzed for response because they did not meet the evaluability conditions. The number classified as complete or partial responders and the resulting response-rate estimate are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies response rate as a participant-count endpoint. In general, a binary endpoint classifies each evaluable participant into categories such as response or no response. A response-rate estimate is the count meeting the response definition divided by the relevant analysis denominator. That denominator matters: it determines which participants contribute to the estimate and affects its uncertainty. In this study, the registry explains why two patients were excluded from response evaluation, but the response count and analysis denominator are not reported in the registry record.

How does RECIST define response?

The endpoint applies revised RECIST version 1.1, a standardized approach for assessing changes in measurable tumor lesions. Complete response means that all target lesions have disappeared, subject to the stated lymph-node criterion. Partial response requires at least a 30% decrease in the sum of target-lesion diameters relative to baseline. Progressive disease requires at least a 20% increase relative to the smallest sum recorded on study and an absolute increase of at least 5 mm. Stable disease is the category that meets neither the partial-response nor progressive-disease threshold. These rules help make response classification explicit rather than relying on an informal judgment that a tumor has improved or worsened.

The primary outcome combines complete and partial response. It is assessed every 8 weeks, according to the registry. The record does not state how repeated assessments were incorporated into the final response classification, whether confirmation of response was required, or what handling rules applied to missing assessments. Those details are not reported in the registry record and should not be inferred from the endpoint name alone.

What can a confidence interval tell a reader?

In general, a confidence interval communicates the statistical uncertainty around an estimate. For a response rate, it would describe a range of values compatible with the observed responder count and the method used to calculate the interval. A narrow interval indicates greater precision than a wide interval, while neither width nor location alone addresses the limitations of a single-group design. The registry record does not report a response estimate or confidence interval, so the precision of the primary result cannot be assessed from the record.

For binary outcomes, statistical methods typically account for the fact that each participant contributes a category rather than a continuous measurement. The exact method can matter, especially when counts are small or near the boundaries of possible rates. The registry record does not report a method for estimating response uncertainty, an adjustment strategy, or a complete statistical analysis plan. No particular method should be attributed to the investigators on the basis of the record.

Why does the single-group design matter statistically?

A single-group study can estimate outcomes within the treated group, subject to the endpoint definition and the analysis population. It cannot directly estimate a randomized between-group contrast because there is no separate control arm. A response observed after treatment is not, on its own, a measure of the difference treatment caused. General statistical adjustment cannot recreate the protection against confounding offered by randomized assignment when the relevant comparator data are absent.

The study title describes a two-stage design. In general, a two-stage Phase II design may use information from an initial stage to determine whether enrollment continues, according to prespecified rules. The registry record does not report such rules, stage sizes, or decision thresholds. It is therefore not possible to assess from the record whether a stage-based stopping rule was used or how it would have influenced the final result.

How should planning calculations be read?

Planning illustrations are distinct from trial results. 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 target effect expressed as a fraction of an observed effect. They are described as illustrations rather than as the trial's own design. In particular, assumptions involving two equally allocated arms do not describe the actual single-group study structure. The illustrations should not be read as observed power, evidence of a treatment effect, or proof that the trial had a particular probability of success. The registry record does not report the trial's own sample-size justification.

General power calculations depend on an assumed effect, a variability model, an error-rate target, and a design. If an assumed effect is based on an observed result, planning for a smaller fraction of that effect can illustrate sensitivity to a less optimistic target, but remains hypothetical. The output of such a calculation is a planning quantity, not an additional set of observed participants or events. Here, no numerical planning result is reported in the registry record, and none should be substituted for the missing response outcome.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists response rate as the primary outcome and progression-free survival and overall survival as secondary outcomes. It also records four outcome measures, but the additional outcome measure details are not reported in the registry record. The record does not describe a multiple-testing strategy or explain how interpretation across several endpoints was handled. When several outcomes are examined, the chance of at least one apparently notable result can increase; in general, a prespecified hierarchy or adjustment can help address that issue. No such approach should be assumed for this study.

The record gives a response-evaluability rule: two patients were not analyzed because they lacked one or more of measurable disease at baseline, at least one cycle of therapy, and disease re-evaluation. It does not report the reasons for each patient's non-evaluability, the outcome denominator, or a broader analysis-population definition. The registry record also does not report how missing or unevaluable response assessments were handled beyond the stated exclusion.

The endpoint was scheduled for assessment every 8 weeks, but the record does not explain how missed visits, incomplete lesion measurements, or assessments after discontinuation were treated. These details can affect an endpoint based on repeated evaluations. They are not reported in the registry record, so the impact of missing assessments on the response estimate cannot be determined.

No outcome analyses are recorded in the registry entry. The analysis plan, including any prespecified adjustment, subgroup analysis, or interim analysis, is not reported in the registry record. The title's description of a two-stage study is not enough to establish the decision rules or to determine whether interim testing affected multiplicity. The outcome findings and the analysis populations therefore cannot be fully evaluated from the registry entry.

11. 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 4% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pleural effusion (5.3%).

The registry lists 19 participants at risk in the arsenic trioxide group for the serious adverse-event entry, with 1 participant affected. For the other adverse-event entry, it lists 19 at risk and 7 affected. These are counts recorded in separate adverse-event categories. The record does not say whether the affected participants in those categories overlapped, so the counts should not be combined or interpreted as counts of different people.

Pleural effusion is listed as the leading serious adverse-event term, at 5.3%. That figure is quoted as recorded; the registry entry does not provide further detail in the information available about the event count behind the term or its clinical course. The deaths field is not reported in the registry record.

Adverse-event counts are descriptive. In a single-group study, they do not show how the frequency compares with another treatment or with the frequency that would have occurred without study treatment. The at-risk counts also do not establish the time each participant was observed or the exposure period used for counting events. The registry record does not report those details. These entries should therefore be read as the recorded safety counts and term, not as a comparative estimate of harm or a complete account of safety.

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

The registry record documents a Phase II study of arsenic trioxide in previously treated small cell lung cancer and specifies how its primary response endpoint was defined. It also records selected adverse-event counts. These details are useful for understanding the study's question, outcome definitions, and structure. They do not supply the primary outcome result: the number of complete or partial responders and the response-rate estimate are not reported in the registry record.

Without the endpoint count, denominator, and uncertainty estimate, the magnitude and precision of response cannot be judged. The fact that the study was completed does not itself establish what the response findings were. Likewise, the registry's listing of progression-free survival, overall survival, and biomarker aims does not establish any result for those outcomes.

The single-group design also limits causal interpretation. Even if a response count were available, outcomes in a treated group alone would not provide a randomized comparison against another treatment or against no study treatment. The registry record cannot establish that an observed outcome was caused by arsenic trioxide rather than by other influences.

The safety entries show that the record lists affected participants in serious and other adverse-event categories, and identifies pleural effusion at 5.3% among the leading serious terms. They are not comparative estimates and do not by themselves describe the full timing, severity, or course of all adverse events. The record does not report deaths in the relevant field.

The appropriate reading is therefore bounded: the study question and endpoint rules are described, and some safety information is recorded, but the registry does not report the efficacy outcomes needed to characterize response or survival. No conclusion about treatment benefit or lack of benefit follows from the absence of these results in the registry entry.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the gap between a clearly stated clinical question and the evidence available in a registry record. The primary outcome has a recognizable definition: response combines complete and partial response under revised RECIST version 1.1, with assessment every 8 weeks. Such explicit criteria are important because outcome classification can otherwise depend on subjective or inconsistent judgments.

The evaluability rule also makes the analysis population consequential. The registry states that two patients were not analyzed for response unless they had measurable disease at baseline, received at least one cycle, and had disease re-evaluated. That distinction between enrollment and endpoint analysis is a basic feature of clinical-trial interpretation. Yet, without a reported response denominator and count, the reader cannot quantify the effect of the evaluability rule on the reported estimate.

The single-arm design illustrates a second important principle: a within-group outcome is not equivalent to a treatment-versus-control effect. A concurrent comparator can help separate treatment differences from other explanations for outcomes. Its absence does not make descriptive results meaningless, but it restricts the claims the design can support.

Finally, the record demonstrates why completeness matters. It identifies secondary survival outcomes and biomarker aims, but does not report their findings or analysis details. The title describes a two-stage design, while the decision rules are not reported in the registry record. Statistical readers need both endpoint definitions and the results, analysis populations, and methods used to produce them. Without those elements, the design can be described, but the main efficacy result and its precision cannot be assessed.

14. 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 trial-specific limitation in the registry record is the absence of primary response results. Although response rate is named and defined, the registry does not report responder counts, the response denominator, an estimate, or its uncertainty. The registry entry therefore cannot support a quantitative assessment of the primary endpoint.

The response analysis excludes two patients under stated evaluability conditions. The registry does not give further detail about why each was not evaluable or how those exclusions affected the analysis. It also does not report the method for handling missing assessments, the final response classification procedure, or whether response confirmation was required. These omissions make it difficult to assess the robustness of the endpoint analysis.

The study is single-arm and unmasked, with no separate comparator group. This limits comparative and causal interpretation. The record does not report detailed dosing, the full protocol, eligibility criteria, or the study's sample-size justification. Although the official title calls the design two-stage, stage-specific rules and interim decision procedures are not reported in the registry record.

Progression-free survival and overall survival are listed as secondary outcomes, but their definitions and results are not reported in the registry record. Biomarker aims are described without reported findings. The record also lists four outcome measures, while the full details of all measures are not available in the entry summarized by these registry entries. Analysis plans, multiplicity handling, and outcome-level statistical methods are not reported.

Safety information is limited to the listed at-risk and affected counts and the leading serious term. The deaths field is not reported in the registry record, and the details needed to interpret exposure time, event timing, and participant overlap are absent. These limitations concern what this registry record can establish; they should not be mistaken for proof that information was never collected elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Arsenic Trioxide in Small Cell Lung Cancer — NCT01470248.
• Registry record last updated 2021-02-17; status last verified 2021-02.
• Results first posted 2017-03-08.
• 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.

18. Record Summary

This is the registry record for a completed, single-arm Phase II study of arsenic trioxide in previously treated small cell lung cancer, sponsored by Emory University. The recorded enrollment is 20; the study brief describes an intended maximum of 36 participants. The recorded start was 2011-08 and primary completion was 2016-01.

Response rate, assessed every 8 weeks under revised RECIST version 1.1, was the primary outcome. Two patients were not analyzed for response because they did not meet the stated evaluability conditions. The registry does not report the response count or estimate. Progression-free survival and overall survival are listed as secondary outcomes, without results in the registry record.

The safety entry lists 1 of 19 at risk as affected in the serious adverse-event category and 7 of 19 in the other adverse-event category; pleural effusion is listed at 5.3% among serious terms. The record does not report a comparator, the outcome analysis plan, or the study's stage-specific rules. It describes the design and selected safety information, but not the primary efficacy findings needed to assess response.