Low Dose Arsenic Trioxide as a Potential Chemotherapy Protector: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Low Dose Arsenic Trioxide as a Potential Chemotherapy Protector (NCT01428128), a na phase 2 study. The primary outcome is Dose of Arsenic That Blocks Activation of p53.

2. Clinical Question

In general, a biomarker-based question asks whether a measurable biological feature changes in the way anticipated. Such a measure may help characterize a biological response, but it is not by itself a measure of cancer control, symptoms, or long-term clinical outcomes. The registry description gives the rationale that p53 is involved in responses to cell damage and proposes that lower-dose arsenic trioxide might block its activation. That proposed rationale should be distinguished from a demonstrated result in participants. Because the primary outcome result is not reported in the registry record, the biological question remains unanswered by the posted results.

3. Trial Design

This is a Phase II study recorded as completed. It used a single-group model, with allocation listed as not applicable and masking listed as none. The registry record gives enrollment as 50 and identifies arsenic trioxide as the intervention. It does not identify a separate control arm or a randomized allocation process. The stated study population is patients with malignancies; the listed condition is cancer other than leukemia.

The primary objective was to find a dose of arsenic that blocks activation of p53, measured by Western blot, on Day 1 of chemotherapy. A secondary outcome is listed as a complete blood count (CBC). The registry record lists two outcome measures, but it does not report the results for the primary outcome or provide a CBC result in the registry record for interpretation. The intervention description does not specify the administered dose, timing before chemotherapy, duration, or dose-adjustment rules. Those details are not reported in the registry record.

The study began in 2011-04, and primary completion is recorded as 2013-01. The sponsor is The University of Texas Health Science Center at San Antonio. The record is marked completed. These administrative details identify the study’s registered status and timeline; they do not establish that a result was reported for every registered outcome.

For a single-group study, outcome observations can describe what was recorded among participants receiving the study intervention. Without a separate comparison group, the design does not directly estimate how outcomes would have differed under another treatment or no intervention. General statistical interpretation therefore depends on the clarity of the measured outcome, the number of participants contributing data, and how those observations were analyzed. The registry record does not report an analysis population, an analysis method, or a primary outcome estimate. Accordingly, the design can be described, but the magnitude and precision of its primary finding cannot be evaluated from the posted results.

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: No baseline p52 activation in peripheral lymphocytes in culture, but p53 activation inducible upon radiation in culture.

Overall Study

Reasons for not completing this period:

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: Excluded: screen failures, withdrawals for any cause prior to completion of 2 chemotherapy cycles, or received Neulasta for only one cycle. Note: The 2 patients who received Neulasta for only one cycle and were not evaluable, were included in the adverse event numbers since they received study drug. Participant number will be 35 for AE module.

6. Primary Endpoint

The registry lists the primary outcome as Dose of Arsenic That Blocks Activation of p53, measured over Day 1 of chemotherapy.

The primary outcome is titled “Dose of Arsenic That Blocks Activation of p53.” It is expressed in mg/kg, is classified as a number, and has a timeframe of Day 1 of chemotherapy. Its description states that the objective is to find a dose that blocks p53 activation, with blockage assessed through reduced p53 production measured by Western blot.

In general, a dose-finding endpoint seeks to identify an amount of an intervention associated with a specified biological response. A Western blot is a laboratory method for assessing a protein; in this study, it is the stated means of measuring p53 production. The endpoint therefore concerns a biomarker response at a specified time, rather than a direct measure of symptoms, cancer progression, or survival. A biomarker can be useful for investigating a biological mechanism, but interpretation depends on how the response was defined and measured, and whether the reported change is tied to a clinically meaningful outcome.

The registry record does not report the primary outcome value, the criterion used to define “blocks,” or the number of participants contributing measurements at each dose. It also does not report a measure of uncertainty around a dose estimate. Without those results, it is not possible to determine which dose, if any, met the study’s stated objective or how precisely that dose was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry records a Phase II, single-group study with allocation listed as not applicable and masking listed as none. These terms describe the recorded design rather than a statistical result. In a single-group design, the registered intervention is not compared with a distinct randomized control group. General statistical interpretation of such a study focuses on the outcomes observed among participants and the uncertainty in those observations. It cannot use a between-group randomized contrast when no comparator group is identified.

What does a single-group design tell us?

General explanation: a single-group study can be used to characterize an outcome after an intervention or to explore a dose-related biological response. However, changes observed over time may also reflect factors other than the intervention, such as the underlying condition, other care, or variation in measurement. A separate control group can help address some of these alternative explanations. The registry record does not identify a control group or report an adjusted comparison. The study’s stated primary objective is dose finding, so the relevant question is the relation between dose and the p53 measure; the registry does not provide the observations needed to evaluate that relation.

How should the primary measure be understood?

The primary outcome is a numeric dose, expressed in mg/kg, intended to block activation of p53. The stated measurement is p53 production assessed by Western blot on Day 1 of chemotherapy. In general, a numeric biomarker endpoint can be described through a measured value, a change, or a model relating the biomarker to an intervention dose. The registry record does not report which analysis was used, the operational threshold for a blocked response, the number of dose levels, or the resulting dose estimate. Those details are necessary to reproduce or evaluate the endpoint analysis.

A confidence interval, in general, describes a range of values compatible with the data and the chosen statistical method. Its width reflects precision: a narrower interval indicates a more precise estimate under that method, while a wider interval indicates more uncertainty. No confidence interval or other uncertainty measure for the primary dose is reported in the registry record. It is therefore not possible to assess statistical precision for the main question.

What can the safety counts show?

The registry gives one arsenic trioxide group, with 35 participants at risk and 9 affected for serious adverse events. For other adverse events, it gives 35 at risk and 35 affected. The listed serious-event terms include device related infection and lung infection, each recorded as 5.7%, and hypotension, pneumonitis, infusion site extravasation, and non-cardiac chest pain, each recorded as 2.9%. These are descriptive summaries. In general, event counts and percentages depend on the definitions used, the period of observation, and the population included in the denominator. The registry record does not report those details or provide a comparison group for these safety figures.

General statistical methods for comparing event frequencies may account for the size of each group and the uncertainty around each estimate. Such comparisons require suitable groups and clear denominators. A percentage alone does not indicate whether an event was caused by treatment, and a listed event does not establish a difference from another treatment. Here, the registry record gives no comparative safety estimate.

What does the analysis listing mean?

The registry lists zero analyses. This means there are no analysis results listed in the registry record for interpretation; it should not be taken to mean that no analysis was conducted outside the registry. The statistical methods used for the primary outcome are not reported in the registry record. It is also not reported whether the analysis was prespecified, whether measurements were transformed, how repeated measurements were handled, or whether any covariates were included.

General explanation: when measurements vary more than a standard model expects, a model that allows over-dispersion may better represent the variability and may produce more realistic uncertainty estimates. Whether over-dispersion is relevant depends on the outcome and the model. The registry record does not describe a model or an observed distribution for the primary measure, so no conclusion about over-dispersion or a suitable model can be drawn for this study.

Sample-size calculations are planning tools, not evidence about what was observed. A planning illustration based on an observed effect, when available, describes how a hypothetical study might be sized under stated assumptions; it is not “observed power” and does not substitute for an estimate with an uncertainty interval. The registry record does not report its own sample-size justification or statistical design assumptions. The enrollment of 50 is a registered enrollment figure, not by itself evidence that the study had adequate precision for its primary question.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary dose-of-arsenic measure and a secondary complete blood count (CBC). It also lists zero analyses. No outcome analysis results are reported in the registry record for interpretation. The registry record does not report whether there were additional endpoints, repeated measurements, subgroup analyses, or interim analyses, and it does not describe an analysis plan.

In general, multiplicity arises when several outcomes, time points, doses, or statistical tests are considered. Testing many hypotheses can increase the chance of at least one apparently unusual result even when no corresponding effect exists. Statistical plans may address this through prespecified priorities or adjustment methods. The registry record does not report whether any such approach was planned or used. With no analysis results listed, there is no basis for evaluating the impact of multiplicity on the reported findings.

The record does not report the number of participants with usable primary outcome measurements, the number contributing CBC data, or how missing measurements were handled. It also does not describe an analysis population, such as whether analyses included all enrolled participants or only participants with available measurements. These omissions matter because the amount and pattern of missing data can affect both the estimate and its precision. General statistical methods for missing data rely on assumptions about why observations are absent; without information about the missingness pattern and the analysis method, those assumptions cannot be assessed.

Enrollment is recorded as 50, while the safety summaries list 35 at risk for each event grouping. The registry record does not explain this difference or identify the populations used for the primary and secondary outcomes. The denominators should therefore be interpreted only as reported for their respective safety summaries, not as the number analyzed for other outcomes.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: device related infection (5.7%), lung infection (5.7%), hypotension (2.9%), pneumonitis (2.9%), infusion site extravasation (2.9%).

The registry reports serious adverse events for the arsenic trioxide group with 35 participants at risk and 9 affected. For other adverse events, it reports 35 at risk and 35 affected. The serious-event terms listed are device related infection and lung infection, each at 5.7%; hypotension, pneumonitis, infusion site extravasation, and non-cardiac chest pain, each at 2.9%. These figures describe the registry entries and their recorded denominators.

In general, an “at risk” denominator indicates the group counted for a particular adverse-event summary, while “affected” denotes participants recorded as having an event under that summary. The registry record does not provide the observation period, event definitions, event severity grading criteria, or the relationship between the safety denominator and the enrollment of 50. It also does not explain whether participants could contribute to more than one event term. The percentages should be read as the registry reports them, without recalculation or combining categories.

These are descriptive safety figures from a single-group study. They do not establish that arsenic trioxide caused the listed events, and there is no separate comparator group in the registry record to support a relative safety comparison. The registry does not report deaths in the safety summary.

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

The registry record establishes that a Phase II, single-group study was conducted to investigate low-dose arsenic trioxide as a potential chemotherapy protector. Its primary objective was to identify a dose that blocks p53 activation, with p53 production assessed by Western blot on Day 1 of chemotherapy. The record also identifies a CBC as a secondary outcome and provides descriptive adverse-event summaries for the arsenic trioxide group.

The record does not report the result for the primary measure. It therefore does not identify a dose that met the stated objective, quantify p53 production, or show the precision of any dose estimate. No primary outcome confidence interval, statistical test result, or analysis estimate is reported. The CBC result is also not reported in the registry record for interpretation. These gaps prevent an assessment of whether the biological response described in the study objective was observed.

The design is single-group, with no separate comparator identified. General statistical reasoning cautions that observations in one group do not provide a randomized estimate of how outcomes would compare under another treatment or no intervention. The study’s findings, if reported, would need to be interpreted in light of that design and the available measurements. The posted safety counts do not establish that the intervention caused the events or that event occurrence differed from another treatment.

The reported enrollment of 50 describes the registered study enrollment. It does not reveal the number contributing data to each outcome. The safety summaries list 35 at risk, and the registry record does not explain the denominators or provide information about missing outcome data. A complete assessment would require the primary outcome results, the analysis method, the number analyzed, and measures of uncertainty. In general, those details allow readers to distinguish the observed estimate from the range of values consistent with the data.

Accordingly, the registry record supports a description of the research question, design, and reported safety counts, but it does not support a conclusion about the primary biological result or its precision. This is a limitation of what is reported, not evidence that the primary outcome did or did not occur.

13. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a biologically focused dose-finding question and a clinical comparison question. The registered objective concerns identifying a dose associated with blocking p53 activation, measured by Western blot. Such an endpoint can investigate a proposed biological mechanism. It is not interchangeable with a clinical outcome, and interpretation of a biomarker does not alone establish effects on symptoms, cancer outcomes, or other patient-centered measures.

The single-group design makes the distinction especially important. A dose-finding study can describe a measured response across doses if those data and the analysis are reported. A controlled comparison answers a different question by comparing outcomes between groups. The registry record identifies no separate comparator and reports no primary dose-response results, so readers cannot assess either the biomarker pattern or its precision from the posted results.

The record also illustrates why denominators matter. Enrollment is recorded as 50, while the adverse-event summaries use 35 participants at risk. Without an explanation of which participants contributed to each analysis, the enrollment count should not be substituted for the safety denominators or assumed to be the primary outcome analysis population. In general, clear denominators help readers understand the scope of each estimate and judge how representative it may be.

Finally, a completed registry record can describe a study without reporting its outcome analyses. Here, zero analyses are listed, and the primary measure’s result is not reported in the registry record. That limits evaluation of the study’s statistical evidence, regardless of its stated rationale. The distinction between a registered objective, a descriptive safety summary, and an analyzed outcome is central to interpreting clinical research records accurately.

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 primary limitation for interpretation is the absence of a reported result for the main dose-finding outcome. The registry specifies the endpoint, unit, measurement method, and timeframe, but not the dose estimate, p53 measurement, response criterion, or uncertainty around the estimate. Without those items, the stated objective cannot be evaluated from the posted results.

The study is recorded as single-group, with no masking and no separate comparator. This design does not provide a randomized between-group comparison. The registry record also does not report the administered dose levels, timing or duration of arsenic trioxide, or how dose selection was performed. These are not reported in the registry record, so the dose-finding procedure cannot be reconstructed from the available description.

Although enrollment is listed as 50, the number contributing to the primary outcome is not reported. The safety summaries each list 35 participants at risk; the record does not explain why that denominator differs from enrollment or whether the same participants contributed to each outcome. The missing-data approach and analysis population are not reported. Consequently, the potential effects of incomplete measurements on the estimates cannot be assessed.

The registry lists a CBC as a secondary outcome but does not report its result in the registry record for interpretation. It lists zero analyses, and the statistical methods, any multiplicity approach, and any sample-size justification are not reported in the registry record. The serious adverse-event figures are descriptive, and the event observation period and definitions are not reported. These reporting gaps limit assessment of efficacy-related outcomes, statistical precision, and safety context.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Low Dose Arsenic Trioxide as a Potential Chemotherapy Protector — NCT01428128.
• Registry record last updated 2017-12-13; status last verified 2017-11.
• Results first posted 2014-07-18.
• 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 a completed Phase II, single-group study of arsenic trioxide in patients with malignancies, with cancer other than leukemia listed as the condition. Enrollment is recorded as 50. The primary objective was to find a dose that blocks p53 activation, measured by Western blot on Day 1 of chemotherapy. A complete blood count is listed as a secondary outcome.

Allocation is listed as not applicable, masking as none, and no separate comparator is identified. The study began in 2011-04, with primary completion in 2013-01. The sponsor is The University of Texas Health Science Center at San Antonio.

The registry record does not report the primary outcome result or a CBC result in the registry record for interpretation. It lists zero analyses. Safety summaries report 35 at risk and 9 affected for serious adverse events, and 35 at risk and 35 affected for other adverse events. The registry does not explain the safety denominators or report a comparative safety analysis.