Ipilimumab and Local Radiation for Selected Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ipilimumab and Local Radiation for Selected Solid Tumors (NCT01769222), a non-randomized phase 1 study. The primary outcome is Dose-limiting Toxicity.

2. Clinical Question

The central clinical question was whether intratumoral ipilimumab could be evaluated for safety in the phase 1 component and whether a subsequent combination with local radiation could be studied in the selected cancers. The registry describes these aims, but it does not report a numerical primary endpoint result or phase 2 outcome results. The available record therefore describes the intended questions more fully than it answers them.

3. Trial Design

The registry describes a phase 1/2 study, while its phase field lists PHASE1. The design is nonrandomized, unmasked, and single-group. Stanford University is the sponsor. The study started in 2013-02, had a primary completion date of 2014-11, and is listed as terminated. The reason for termination is not reported in the registry record.

The phase 1 component was described as a safety component. Participants received ipilimumab 25 mg intratumorally on Day 1. The planned phase 2 component was described as treatment-escalation and combined intratumoral ipilimumab 25 mg on Day 1 with local radiation. The registry specifies 10 Gy/fraction within 48 hours for at least 3 fractions. The registry states that the study did not proceed to phase 2. The adverse-event record lists 3 participants at risk in the ipilimumab 25 mg group and none in the combination group.

The enrollment is 3. Because allocation was not randomized and the study is recorded as single-group, there is no randomized control group for estimating a comparative treatment effect. The phase 1 and intended phase 2 regimens should not be interpreted as treatment arms in a head-to-head comparison: the latter had no participants in the posted adverse-event data, and the registry explicitly says phase 2 did not proceed.

The registry lists six outcome measures, including the primary safety endpoint and secondary measures for phase 2. It reports no analysis records. Details such as the reason for termination, a fuller statistical plan, and any rationale for the planned enrollment 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.

Study Phase 1

Study Phase 2

Analysis population for the primary outcome, as defined in the registry: This study did not proceed to Phase 2 (ipilimumab plus radiation combination therapy).

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 Dose-limiting Toxicity, measured over 4 weeks.

The primary endpoint is dose-limiting toxicity, expressed as the percentage of phase 1 participants experiencing dose-limiting toxicities or serious adverse events during 4 weeks. The description says these events were to be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. A safety endpoint of this kind is used to characterize clinically important harms during a defined observation period. In general, counting participants with specified events helps describe how often the endpoint occurred in the study group; it does not, by itself, establish how the regimen compares with another treatment.

The registry does not report a numerical result for this primary endpoint, nor does it provide separate counts of dose-limiting toxicities and serious adverse events for the endpoint. The posted adverse-event information includes a serious-event count and an other-adverse-event count, but the latter is not a substitute for the endpoint result: the registry does not identify that event as dose-limiting. The primary endpoint’s percentage and the event-level details needed to interpret it are therefore not reported in the registry record.

The registry also names phase 2 outcomes for immune response, response rate, overall survival, and duration of response. Since the record states that the study did not proceed to phase 2, those planned outcomes do not provide phase 2 findings.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a binary participant-level outcome: a participant either meets the endpoint definition during the stated observation period or does not. The registry expresses the primary outcome as a percentage of participants. In general, a percentage can make an event frequency easier to understand, but it depends on both the number of participants who meet the definition and the number evaluated. The registry does not report the primary endpoint’s numerator or percentage, so that result cannot be reconstructed from the posted adverse-event counts.

What does a confidence interval add?

In general, a confidence interval describes the uncertainty around an estimate, such as an event percentage. It helps distinguish a precise estimate from one based on sparse observations. When few participants are observed, the estimate may be highly uncertain even when the recorded number of events is low. No confidence interval for the primary endpoint is reported in the registry record. Without it, readers do not have a registry-reported range showing the uncertainty around the endpoint estimate.

What can a single-group study estimate?

A single-group study can describe what happened among the participants who received the study regimen. It does not, on its own, show what would have happened to comparable participants under a different regimen or without the study intervention. Random allocation is one method used in comparative trials to reduce systematic differences between treatment groups. This study is recorded as nonrandomized and single-group, so its data should be treated as descriptive rather than as a randomized treatment comparison. The intended phase 2 combination does not create a valid comparator because the study did not proceed to that phase.

How should zero events be understood?

A zero observed count means no event was recorded in the specified group during the reported observation, not that the underlying event risk is zero. General statistical reasoning treats a zero count from a small group as uncertain evidence: additional observations could reveal events that were not seen in the enrolled participants. The phase 1 safety group included 3 participants at risk for serious adverse events. The registry reports 0 serious adverse events in that group, but does not report an uncertainty interval for this count or rate.

What do the listed planning assumptions mean?

In general, a sample-size calculation asks how many participants may be needed to detect a specified difference under chosen assumptions. The record’s planning description refers to a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of an observed effect. Such planning calculations are illustrations, not trial outcomes, and are not observed power. The registry does not report a trial-specific sample-size justification. With no randomized comparison and no phase 2 enrollment, a planning calculation cannot supply evidence of a treatment effect or turn the posted safety counts into a comparative result.

Why does over-dispersion matter in general?

Over-dispersion occurs when observed variation is greater than a statistical model expects. In general, if a model assumes less variability than the data contain, standard errors can be too small and uncertainty can be understated. It can arise in settings where outcomes vary across participants or clusters more than a simple model allows. The registry record does not report a model-based analysis, an over-dispersion assessment, or an adjustment for it. The concept is therefore relevant as general statistical context, not as a finding about this study.

What does the absence of analysis records imply?

The registry lists 0 analyses. That means the record does not provide analysis entries from which to review an estimated primary endpoint, confidence interval, or hypothesis test. It does not establish that investigators performed no analyses outside the registry; it means such analyses are not reported in the registry record. No p-value or adjusted treatment estimate is available for interpretation. The endpoint description and adverse-event counts should therefore be read as separate pieces of registry information, not combined into an unreported analysis.

Finally, the registry names six outcome measures, but does not describe a statistical analysis plan for them. In general, a statistical plan specifies how outcomes are defined, analyzed, and reported before results are interpreted. The record does not report details such as planned estimation methods, handling of missing observations, or rules for choosing analysis populations. Those omissions limit the ability to evaluate how a numerical endpoint result would have been produced, even apart from the absence of a reported primary result.

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("Ipilimumab 25 mg")
n      <- c(3)
events <- c(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  Ipilimumab 25 mg  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 six outcome measures and names several secondary phase 2 outcomes, including immune response, response rate, overall survival, and duration of response. Immune response appears twice in the listed secondary outcomes. The record does not report a multiplicity strategy, such as whether outcomes were designated as confirmatory or exploratory or whether any adjustment for testing multiple outcomes was planned. Without that information, the interpretation of multiple potential statistical tests cannot be assessed. In any case, the record reports no analysis entries and says that phase 2 did not proceed.

Missing-data methods are not reported in the registry record. The record does not describe how missing endpoint observations, withdrawals, or participants without complete follow-up would be handled. The primary endpoint has a 4-week timeframe, but the registry does not provide participant-level follow-up information or a missingness summary. The absence of such information does not establish that data were missing; it means the registry does not explain whether or how missing observations were considered.

The primary endpoint description identifies phase 1 participants as the relevant population. The registry does not report further analysis-population definitions, such as criteria for inclusion in an endpoint analysis, or whether all enrolled participants were evaluated. The listed enrollment is 3, and the safety record lists 3 participants at risk in the phase 1 group, but this alone does not supply a full analysis-population specification. No details on protocol deviations or exclusions are reported in the registry record.

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 non-serious adverse event terms

For the ipilimumab 25 mg group, the registry lists 3 participants at risk for serious adverse events and 0 affected participants. For other adverse events, it lists 3 participants at risk and 1 affected participant. These are counts in distinct registry categories; the other-adverse-event count should not be mistaken for the number of dose-limiting toxicities. The registry does not identify whether the other event met the primary endpoint definition.

The planned ipilimumab 25 mg and radiation therapy group has 0 participants at risk in the posted adverse-event data. A count of 0 events in a group with no participants is not evidence that the combination caused no events or was safe. The study did not proceed to phase 2, according to the registry.

The record lists no serious adverse-event terms. It also leaves deaths unreported in the adverse-event entries; this is not the same as a reported count of zero deaths. These details should be read as registry reporting categories, not as a complete clinical narrative. The small phase 1 group and absence of phase 2 participants limit what the event counts can establish about safety.

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

The registry records an early study focused on safety for intratumoral ipilimumab, with local radiation planned for a subsequent phase. Three participants were enrolled, the phase 1 group had 0 serious adverse events recorded, and 1 participant had an other adverse event recorded. The registry does not report the primary endpoint percentage or a separate dose-limiting toxicity count. These data describe the posted record, but do not provide a full estimate of the primary safety outcome.

The results do not establish how the regimen compares with another treatment. The study was nonrandomized and single-group, and there was no randomized control group. Nor do the data establish an outcome for the ipilimumab-plus-radiation combination: the registry says the study did not proceed to phase 2, and no participants are recorded at risk in that group.

The record lists phase 2 outcomes related to immune response, response rate, overall survival, and duration of response, but it does not provide results for them. These remain planned outcomes rather than findings. Similarly, the terminated status does not explain why the study stopped; the reason is not reported in the registry record.

In general, a small descriptive safety record can identify events that were observed, but it cannot rule out uncommon events or precisely estimate event frequency. A zero count should not be interpreted as proof that an event cannot occur. The absence of a confidence interval, primary endpoint result, and analysis entries further limits statistical interpretation. The defensible conclusion is therefore about the scope and content of the registry record, not whether a treatment is effective or ineffective.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a research question and the evidence needed to answer it. The registry describes a safety-focused phase 1 component and a planned phase 2 combination component, but the study did not proceed to phase 2. Consequently, the record contains no phase 2 outcome findings for the stated immune and tumor-response measures.

It also shows why the denominator matters when reading event counts. The phase 1 record includes 3 participants at risk for serious adverse events, whereas the planned combination group includes none. A zero event count with participants at risk and a zero count where no participants were observed have different meanings. Neither should be converted into a claim that a regimen has no safety risk.

Another statistical lesson is that event counts, endpoint definitions, and analysis results are not interchangeable. The primary endpoint combines dose-limiting toxicities or serious adverse events over 4 weeks. The posted other-adverse-event count does not tell readers how many participants met that composite definition. Without a reported endpoint result, uncertainty estimate, or analysis record, the intended safety question cannot be evaluated from those counts alone.

Finally, nonrandomized single-group data have a descriptive role but do not establish comparative effects. The phase 1 experience can be described among enrolled participants; it cannot serve as a randomized test of benefit or harm relative to another treatment. Clear distinctions among planned outcomes, observed counts, and unreported analyses are essential when interpreting a terminated early-phase study.

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 enrollment of 3 leaves the safety experience based on very few participants. Such a small group provides limited information about event frequency and cannot reliably characterize less common harms. The registry reports a serious-event count, but does not provide an uncertainty interval or the primary endpoint percentage. The primary endpoint includes dose-limiting toxicities or serious adverse events, yet separate dose-limiting toxicity counts are not reported.

The design is nonrandomized and single-group, so there is no like-for-like control group for comparison. The intended combination regimen cannot be evaluated from the posted participant data because the registry says the study did not proceed to phase 2 and shows no participants at risk in that group. The listed secondary phase 2 outcomes have no reported results.

The status is TERMINATED, but the reason is not reported in the registry record. The record also does not report a statistical analysis plan, a sample-size justification, missing-data methods, detailed analysis-population definitions, or a multiplicity strategy. It lists no analyses. These omissions prevent a detailed assessment of how the planned endpoint and other outcomes were to be analyzed.

The condition list spans numerous lymphoma categories as well as melanoma and colorectal cancers. The registry does not provide participant-level diagnoses or outcome results by diagnosis, so the enrolled group’s disease composition and any variation by condition cannot be assessed. The limitations are therefore both statistical and reporting-related: the small descriptive experience is not accompanied by the endpoint and analysis details needed for a fuller interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ipilimumab and Local Radiation for Selected Solid Tumors — NCT01769222.
• Registry record last updated 2024-01-24; status last verified 2024-01.
• Results first posted 2017-03-03.
• 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

This is a Stanford University-sponsored, nonrandomized, unmasked, single-group study recorded as phase 1. It enrolled 3 participants and is listed as TERMINATED. The phase 1 regimen was intratumoral ipilimumab 25 mg on Day 1. The planned phase 2 regimen added local radiation, but the registry states that phase 2 did not proceed.

The primary endpoint was the percentage of phase 1 participants with dose-limiting toxicities or serious adverse events during 4 weeks. The registry does not report a numerical primary endpoint result. The phase 1 adverse-event data list 0 serious adverse events among 3 at risk and 1 participant with an other adverse event among 3 at risk. No participants are listed at risk in the combination group.

Phase 2 secondary outcomes were planned, but results are not reported. The reason for termination, analysis methods, and missing-data procedures are not reported in the registry record.