A Phase I/II Evaluation of ADXS11-001, Mitomycin, 5-fluorouracil (5-FU) and IMRT for Anal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase I/II Evaluation of ADXS11-001, Mitomycin, 5-fluorouracil (5-FU) and IMRT for Anal Cancer (NCT01671488), a na phase 1, phase 2 study. The primary outcome is To Evaluate the Safety of the Addition of ADXS11-001 to Standard Chemoradiation for Patients With Anal Cancer..

2. Clinical Question

This is a safety-focused Phase I/II study, not a trial designed in the registry record as a controlled test of treatment effectiveness. Its clinical question is about the experience of participants receiving the combined regimen, including adverse events captured during treatment and follow-up. Because there is no concurrent control group, the reported event counts describe participants in this study; they do not isolate the contribution of ADXS11-001 from chemotherapy, radiation, the cancer, or other factors. The registry record does not report a separate efficacy estimate for the combination.

3. Trial Design

The registry identifies NCT01671488 as a Phase I/II study sponsored by Brown University. It lists anal cancer as the condition, a single-group model, no masking, and allocation as not applicable. Enrollment is recorded as 11. The study began in 2013-02, had a primary completion date of 2018-02, and has a status of terminated. The reason for termination is not reported in the registry record.

The study evaluated ADXS11-001 together with 5-FU, mitomycin and IMRT. The treatment description says the first dose would be given 10-14 days before chemoradiation began, followed by chemotherapy and radiation. The description includes regimen details, but its final schedule text ends mid-sentence; the complete treatment schedule is not reported in the registry record. The brief summary describes the study's purpose as evaluating safety and effectiveness of ADXS11-001 in combination with standard chemotherapy and radiation.

A single-group design means participants are described as receiving the study regimen without a parallel control arm. No randomized allocation is reported, and there is no masking. These features make the study suitable for describing events among treated participants, but they do not support a like-for-like comparison with patients receiving another regimen. The registry lists progression-free and overall survival as secondary outcomes, but it reports no analyses for those outcomes. It also does not report an analysis plan, interim analyses, or a design-based sample-size justification. The enrollment figure describes the study overall; the safety data separately identify 10 participants at risk for serious and other adverse events.

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: Patient's who received treatment on 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.

6. Primary Endpoint

The registry lists the primary outcome as To Evaluate the Safety of the Addition of ADXS11-001 to Standard Chemoradiation for Patients With Anal Cancer., measured over Baseline, then prior to each ADXS11-001 and weekly during radiation. Assessments 1-2 weeks post radiation then 2-6 weeks post vaccine and off study and 30 days post treatment..

The primary outcome is framed as evaluating the safety of adding ADXS11-001 to standard chemoradiation. It is a participant-count outcome, with the unit listed as participants and the measure described as a count. The outcome description says maximal toxicities were evaluated using CTCAE version 4.0. All serious and non-serious adverse events were captured from the date of informed consent through 4 weeks after treatment completion, regardless of causality.

The registry specifies a schedule of assessments beginning at baseline and continuing before each ADXS11-001 dose and weekly during radiation. Further assessments are described after radiation, after vaccination and off study, and 30 days after treatment. This repeated monitoring is relevant to a safety endpoint because adverse events may arise at different points during treatment and follow-up. A participant count is a direct way to report how many treated participants experienced an event; it is distinct from a count of event episodes, which could include repeated events in one person.

The posted record does not give a complete numerical result for the primary maximal-toxicity outcome as described. Instead, it provides adverse-event summaries with participant counts and listed event terms. The registry record does not report a severity distribution for all toxicities or a separate estimate with a confidence interval for the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study with participant-count safety outcomes. The methods below explain what that design and outcome type can show in general; they do not add analyses that are absent from the registry record.

What does a participant count describe?

For an event-based safety outcome, a participant count records how many people experienced an event in the defined observation period. It does not necessarily count every occurrence. If one participant has repeated episodes, a participant-level count and an episode-level count answer different questions. The registry identifies the primary outcome unit as participants, while its adverse-event entries present affected-participant counts. The record does not give a detailed event-level dataset or a separate count of repeated episodes.

Counts are useful for an initial description of safety, especially when the question is whether events occurred among treated participants. Their interpretation depends on the population observed, the event definition, the observation period and how completely events were collected. Here, the primary outcome description specifies CTCAE version 4.0 and says serious and non-serious events were captured from informed consent through 4 weeks after treatment completion, regardless of causality. The registry also describes repeated assessment during treatment and follow-up.

What can a single-group design establish?

In general, a single-group study can describe what happened to participants who received the regimen. Without a concurrent control group, it cannot establish how the observed event frequency compares with what would have occurred under another regimen. It also cannot separate events attributable to ADXS11-001 from events related to chemotherapy, radiation, the underlying disease or other influences. This is a design limitation, not a claim that any particular event was or was not caused by treatment.

Randomization is commonly used to make treatment groups comparable, on average, with respect to measured and unmeasured factors. There is no randomized comparison in this record: allocation is listed as not applicable, and the model is single group. Consequently, no between-group treatment effect can be estimated from the posted design. The absence of a comparator also means that an event count should not be interpreted as evidence that the combination has a different safety profile from another treatment.

How should uncertainty be understood?

General statistical explanation: a confidence interval expresses a range of values compatible with data and a specified statistical procedure. It communicates estimation uncertainty; it is not a guarantee that the true value lies in that particular interval. For participant counts, uncertainty is influenced by the number of participants observed and by the number who experienced the event. The registry record does not report confidence intervals for the safety counts, so their precision cannot be assessed from interval estimates in the posted results.

A p-value, in general, measures how incompatible data are with a stated statistical model or null hypothesis, assuming that model and hypothesis. It is not the probability that a treatment works, and it does not measure clinical importance. The registry record reports no analyses, and it provides no p-values or inferential test results for the primary or secondary outcomes. The safety counts therefore remain descriptive in the posted record.

Why does the sample-size illustration not describe trial power?

The record's planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe a planning illustration based on a stated fraction of an observed effect, not the trial's own design. This study is recorded as single group, so the hypothetical two-arm allocation does not describe its actual design. A planning sample size is not observed power and does not show that the study had a particular probability of detecting an effect after the data were collected. The registry record does not report the trial's sample-size justification or a formal power calculation used in its design.

General statistical explanation: over-dispersion occurs when observed variability is greater than a statistical model assumes. If a model ignores it, uncertainty estimates may be too narrow and tests may be poorly calibrated. This issue can arise in some count-data analyses, but the registry record does not identify a count model, report a dispersion estimate, or present model-based safety analyses. It is therefore a general consideration, not a reported feature of this analysis.

In short, the design and outcome definitions support a descriptive reading of the recorded safety experience. The registry does not provide the additional model details, uncertainty estimates, or comparative analyses needed for broader statistical claims.

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")
n      <- c(10)
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  Treatment  10  10  100.0  69.2  100.0  72.2  100.0  71.5  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a plan for handling multiplicity, such as how statistical testing would account for evaluating more than one outcome. It identifies safety as the primary objective and lists progression-free and overall survival as secondary outcomes, but no analyses are reported for those secondary outcomes. The record lists 3 outcome measures; it does not explain whether all planned measures were collected or how any were prioritized in analysis.

Missing-data methods are not reported in the registry record. The safety summary gives 10 participants at risk for serious and other events, compared with overall enrollment of 11, but it does not explain the difference. The record does not describe how participants with incomplete follow-up, unavailable assessments or treatment discontinuation were handled. No assumptions about missing outcomes can therefore be established from the posted information.

The primary safety population is described as patients who received treatment on study. This is not the same as a report of all enrolled participants, and no further analysis-population definitions are reported. The record does not say whether participants were analyzed according to treatment received, whether any participants were excluded from the safety population, or how protocol deviations were handled.

The registry also does not report interim analyses, stopping boundaries, or a statistical analysis plan. The terminated status alone does not establish why the study ended or whether a statistical rule was used. These omissions limit assessment of selective outcome reporting, missingness, and the analysis decisions behind the posted results.

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: fever (1), hypotension(2) (10.0%), fever (1), hypotension(2) hypokalemia (3) (10.0%), weakness (3), decreased appetite (2), gi bleed(3). anemia(3) (10.0%), nausea (3), dehydration (3), anal mucositis (3), enterocolitis (2) (10.0%), nausea(3),dehydration(3),anal mucositis(3), (10.0%).

The safety summary reports 10 participants at risk for serious adverse events and 10 affected. For other adverse events, it reports 10 at risk and 8 affected. These are participant-level counts as described in the registry, rather than a comparison between treatment groups. The record does not explain why the safety denominator is 10 when total enrollment is 11.

The serious-event list contains multiple event-term groupings, each paired with 10.0%. The parenthetical numbers within those descriptions are part of the registry wording, but the record does not define them. The entries should not be treated as a complete severity profile or as proof of causation. The outcome description says events were captured regardless of causality.

The record also lists deaths as 10, without explaining the circumstances or meaning of that entry. One serious-event term is “Expired unknown reason.” Neither entry establishes cause or treatment relationship. These data are best read as reported safety information with important contextual details unavailable in the registry record.

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

The posted results establish that the registry contains safety-event counts for participants treated in a single-group study of ADXS11-001 with 5-FU, mitomycin and IMRT. The serious-event summary reports 10 affected among 10 at risk; the other-event summary reports 8 affected among 10 at risk. The serious-event listing supplies event terms and 10.0% alongside each entry. These are descriptive observations from the study population, not estimated differences between treatment options.

The figures do not establish which treatment component caused an event. The study combined an investigational agent with chemotherapy and radiation, collected events regardless of causality, and had no concurrent control group. The record does not provide detailed event-level timing, cause, duration, or severity distributions, nor does it clarify the deaths entry. These gaps constrain interpretation of the safety summaries.

The record does not provide results for the listed secondary outcomes of progression-free and overall survival. It therefore does not show an estimate of survival or a comparison of survival between regimens. The stated study purpose includes effectiveness, but a stated purpose is not itself an effectiveness result.

Enrollment was 11, while 10 participants are listed at risk in the safety summaries. The reason for this difference is not reported. The study's terminated status is also recorded without a stated reason. Neither fact, by itself, explains the observed safety entries or the absence of analyses. Overall, the registry supports a limited description of reported events in the treated group, but not a conclusion about comparative safety, treatment effect, or causation.

14. Why This Trial Matters Statistically

This study is statistically important as an example of how a safety-focused Phase I/II study and its registry results need to be read in light of design. A single-group study can record treatment experience, including adverse events, and can provide information relevant to planning later research. Its counts describe what was recorded among treated participants, but without a concurrent comparison they cannot estimate how those counts differ from another treatment strategy.

The distinction between enrollment and the safety denominator matters for transparent interpretation. The registry records enrollment of 11 and identifies 10 participants at risk in the adverse-event summaries, without explaining the difference. Reporting the denominator alongside affected counts helps readers understand the population represented; the unexplained difference makes it important not to assume that every enrolled participant contributed to each safety summary.

It also matters that the stated primary objective and the reported numerical information are not identical. The primary outcome is described as maximal toxicities assessed with CTCAE version 4.0, while the posted safety information consists of event counts and terms. The record does not provide a complete severity distribution or inferential estimates. Likewise, listing progression-free and overall survival as secondary outcomes does not supply results for those outcomes.

Finally, planning assumptions should be distinguished from the actual design. The record's sample-size illustration describes hypothetical equal allocation between two arms, whereas the registered study is single group. Keeping that distinction clear prevents planning calculations from being mistaken for observed power or evidence of a comparative effect. These features make careful, bounded interpretation especially important.

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.

Several limitations are specific to the information reported for this study. The design is single group, with no randomized comparator and no masking. The observed safety counts therefore have no direct concurrent benchmark. Because the regimen includes ADXS11-001, 5-FU, mitomycin and IMRT, the design cannot distinguish the contribution of each component to an observed event.

The registry records enrollment of 11 but reports 10 participants at risk in each adverse-event summary; it does not explain the difference. The primary outcome is described as maximal toxicities assessed using CTCAE version 4.0, but the record does not report a full toxicity-grade distribution or a complete numerical primary-outcome result. The listed serious-event terms include parenthetical numerals whose meaning is not defined in the record.

The adverse-event record lists deaths as 10 and includes “Expired unknown reason,” but does not clarify the death entry's definition, timing, cause, or treatment relationship. The event collection period and assessment schedule are described, but event-specific timing and duration are not reported. The treatment schedule description ends mid-sentence, so the complete regimen details are not available in the registry record.

The status is terminated, with no reason reported. No analyses are reported for progression-free or overall survival, and no inferential results, confidence intervals, missing-data methods, multiplicity plan, interim analyses, or statistical analysis plan are reported. These gaps restrict both clinical interpretation and statistical assessment of the posted findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase I/II Evaluation of ADXS11-001, Mitomycin, 5-fluorouracil (5-FU) and IMRT for Anal Cancer — NCT01671488.
• Registry record last updated 2020-02-17; status last verified 2020-02.
• Results first posted 2017-05-12.
• 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

NCT01671488 is a Brown University Phase I/II, single-group study of ADXS11-001 combined with 5-FU, mitomycin and IMRT for anal cancer. The registry records enrollment of 11, a start date of 2013-02, primary completion in 2018-02, and terminated status. It does not report the reason for termination.

The primary objective concerns safety, with maximal toxicities assessed using CTCAE version 4.0 and adverse events captured regardless of causality. The safety summary lists 10 participants at risk for serious events and 10 affected, and 10 at risk for other events and 8 affected. The record lists progression-free and overall survival as secondary outcomes but reports no analyses for them. No randomized comparison or statistical analysis results are reported.