Pilot Ipilimumab in Stage IV Melanoma Receiving Palliative Radiation Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pilot Ipilimumab in Stage IV Melanoma Receiving Palliative Radiation Therapy (NCT01449279), a na phase 2 study. The primary outcome is Safety Measurement - Percentage of Patients Experiencing Serious Adverse Events (SAEs) in the First 4 Months of Treatment..

2. Clinical Question

The trial is titled “Pilot Ipilimumab in Stage IV Melanoma Receiving Palliative Radiation Therapy” and is sponsored by Stanford University. Its brief summary states that it was designed to determine the safety of local palliative radiation therapy used in combination with anti-CTLA-4 immunotherapy. The registry lists melanoma as the condition and the trial as phase 2.

The study also lists response rate, overall survival, duration of complete response, duration of partial response, stable disease, median time to complete or partial response, and progression-free survival as secondary outcomes. These outcomes raise questions about tumor response and the course of disease, but the record does not provide analysis results for them. The central interpretive question is therefore narrower than whether the combination improves outcomes: the posted safety count describes events observed in this treatment group, while efficacy and comparative effects are not established by the information reported.

3. Trial Design

The registry describes a completed phase 2, single-group study sponsored by Stanford University. Enrollment is listed as 22. The study began in 2011-10, had a primary completion date of 2015-12-31, and its status is COMPLETED. The allocation entry is NA and masking is NONE. These design features indicate that the registry does not describe randomized assignment, masking, or a separate control arm.

The intervention group is named “Ipilimumab Treatment + Radiation Therapy.” The arm description says that ipilimumab was to be administered as standard of care at a base dose of 3 mg/kg intravenously over approximately 90 minutes every 3 weeks for a total of 4 treatments. It describes palliative radiation therapy to 1 to 2 disease sites, starting within 5 days of the first ipilimumab treatment. The final phrase of the recorded arm description is incomplete, so further procedural detail is not reported in the registry record.

The primary outcome is a safety measure: the percentage of patients experiencing serious adverse events during the first 4 months of treatment. Its unit is participants, and the posted result is expressed as a participant count. The registry lists 8 outcome measures, including secondary response and survival outcomes, but reports 0 analyses. Consequently, the record does not provide effect estimates, statistical tests, or analytic results for those listed outcomes.

Because this is a single-group study, its observed event count describes participants treated under the recorded regimen; it cannot estimate a treatment contrast against an untreated or alternative-treatment group. The registry record does not report a sample-size justification, a statistical analysis plan, or details of interim analyses. Any planning illustrations should be distinguished from observations in this completed trial: the stated assumptions describe hypothetical two-arm calculations based on a fraction of the observed effect, not the trial’s own design or observed power.

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: All subjects.

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 Safety Measurement - Percentage of Patients Experiencing Serious Adverse Events (SAEs) in the First 4 Months of Treatment., measured over 4 months.

The primary endpoint is the percentage of patients experiencing serious adverse events during the first 4 months of treatment. Although the endpoint title is framed as a percentage, the posted result is given as a count of participants: 11 of 22 at risk are recorded as having a serious adverse event. No confidence interval or test of this result is reported in the registry record.

The registry’s definition covers events with serious consequences or clinical importance. It includes death, a life-threatening event, hospitalization or prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, and an important medical event that may jeopardize the subject or require intervention to prevent another serious outcome. The definition concerns the seriousness of an event, not whether the event was caused by ipilimumab, radiation, the underlying disease, or another factor. Causal attribution is not reported with the count.

A safety endpoint is used to describe harms observed during treatment and to identify events that merit attention in the study’s safety record. A count is a direct summary of how many participants were recorded as affected, but it does not by itself characterize event timing, duration, severity beyond the stated definition, recurrence, or causal relationship. The endpoint is limited to its specified observation window; conclusions about events outside the first 4 months are not supported by this primary measure.

The group-level count also does not provide a comparison with what might have occurred under another treatment strategy. In a single-group study, this endpoint can describe observed safety experience but cannot isolate the contribution of each component of the combination.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count describe?

A participant count reports how many people in the stated risk group were recorded as experiencing an event. In this trial, the primary outcome is defined over the first 4 months of treatment, and the registry reports 11 affected participants among 22 at risk. This is a direct description of the recorded cohort, not an estimate of what would happen in a different group. The endpoint title uses percentage language, but no recalculation is needed to interpret the posted count, and no additional percentage should be inferred from it.

What does the event definition add?

Safety measures depend on clear definitions. The registry’s serious adverse event definition groups events by their consequences or importance, including life-threatening events, hospitalization, disability, congenital anomaly or birth defect, and other important events that may require intervention. This definition provides a rule for classifying events as serious. It does not, by itself, establish why an event occurred. A serious event can be observed during treatment without the registry summary demonstrating that treatment caused it.

How should uncertainty be understood?

General statistical explanation: an estimate from a study is subject to sampling uncertainty, because the observed participants may not represent every person who could receive the treatment. A confidence interval is a range of values compatible with a method’s assumptions and the observed data; it communicates precision as well as the central estimate. No confidence interval is reported for the primary safety result in the registry record. Without one, readers should not assign a numerical precision range or treat the observed count as an exact estimate of risk in a broader population.

A p-value, when reported, addresses compatibility between data and a specified null model under particular assumptions. It does not measure the probability that a treatment works, establish causality, or describe the size of an effect. The registry record reports no analyses, so it does not provide a p-value for this primary outcome. There is also no reported inferential comparison to interpret.

Why does the single-group design matter?

A treatment contrast requires information about outcomes under different treatment conditions. In this record, participants are described in a single-group design and no control arm is recorded. The observed count consequently describes the treated group without separating treatment effects from other influences. General statistical explanation: random allocation in a comparative study can help balance measured and unmeasured influences on average, while masking can reduce some forms of assessment or reporting bias. Neither randomized allocation nor masking is described in this registry record.

The combination also contains ipilimumab and radiation therapy. A single group receiving both components cannot, by itself, identify the contribution of either component separately. The count is not a direct comparison of the combination with either component alone. Such comparisons are not reported in the registry record.

What is over-dispersion, and is it relevant to this result?

General statistical explanation: over-dispersion occurs when variation in observed data exceeds what a chosen statistical model expects. It can matter for models of counts or rates, because standard errors and confidence intervals may otherwise be too small. The primary result is presented as a participant count rather than a model-based rate, and no model, variance estimate, or analysis is reported. The registry record does not provide enough information to assess over-dispersion or an adjustment for it. It would be inappropriate to assume that a particular model was used.

How do the secondary outcomes fit in?

The registry lists response rate, overall survival, duration of complete response, duration of partial response, stable disease, median time to complete or partial response, and progression-free survival as secondary outcomes. Such outcomes generally describe tumor response or time until a specified event, but their interpretation depends on definitions, follow-up, censoring, and analysis procedures. Those details and outcome estimates are not reported in the registry record. The record lists 8 outcome measures overall and 0 analyses; it therefore does not support numerical conclusions about these secondary outcomes.

What do the planning assumptions mean?

General statistical explanation: sample-size planning asks how much information a future study might need to detect an effect under specified assumptions. The registry’s planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detecting a stated fraction of the observed effect. It describes time-to-event planning in terms of a total event count and other planning in terms of participants per arm. These assumptions do not describe the design used for this single-group trial. Planning illustrations are not observed power and do not demonstrate that a treatment effect exists. The registry record does not report the trial’s own sample-size justification.

Recalculated analyses, when available, are simple unadjusted recalculations from posted summary statistics. They do not replace a sponsor’s analysis; if a discrepancy is identified, the sponsor’s own analysis takes precedence. No such analysis is reported in the registry record for the outcomes.

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 Treatment + Radiation Therapy")
n      <- c(22)
events <- c(9)
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 Treatment + Radiation Therapy  22  9  40.9  20.7  63.6  23.3  61.3  23.2  61.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including a primary safety measure and secondary measures relating to response and survival. When a study evaluates multiple outcomes, the chance of at least one apparently notable result can increase if each is tested without accounting for the number of tests. General statistical explanation: multiplicity procedures can control or otherwise address that issue, but they depend on the analysis plan and the role assigned to each outcome. No multiplicity strategy is reported in the registry record. Since the record reports 0 analyses, there are no posted outcome tests to interpret for multiplicity.

Missing-data handling is not reported in the registry record. The record does not describe whether all participants had complete follow-up for the primary endpoint, how incomplete observations were handled, or whether any imputation or other missing-data method was used. The count is reported alongside 22 participants at risk, but that alone does not establish completeness of follow-up or explain how the risk group was defined operationally.

The primary outcome describes its population as all subjects. The registry record does not provide further analysis-population definitions, such as how participants who did not receive treatment or did not complete follow-up were handled. It also does not report an intention-to-treat population or a per-protocol population. These labels should not be inferred from the stated population description.

Without an analysis plan, results for the secondary outcomes, or missing-data details, it is not possible to assess whether outcome selection, incomplete follow-up, or analytic choices affected the reported safety summary. Those gaps are limitations of what the registry record allows readers to establish; they are not evidence that a particular analysis was or was not conducted outside the record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nausea (18.2%), pain-gastrointestinal-abdomen nos (18.2%), vomitting (18.2%), colitis (13.6%), diarrhea (13.6%).

The primary safety result records 11 participants with serious adverse events among 22 at risk during the first 4 months of treatment. The registry defines serious events using consequences such as death, life-threatening events, hospitalization or its prolongation, disability, congenital anomaly or birth defect, and other important events requiring intervention or potentially jeopardizing the subject. The count describes participants recorded as affected; it does not establish that treatment caused the events.

The listed serious adverse event terms are Nausea, 18.2%; PAIN-GASTROINTESTINAL-Abdomen NOS, 18.2%; Vomitting, 18.2%; Colitis, 13.6%; Diarrhea, 13.6%; and Pancreatitis, 4.5%. The record does not state in this summary whether terms overlap within participants, so these percentages should not be added or treated as mutually exclusive categories.

For other adverse events, the group record lists 22 at risk and 22 affected. It also lists 13 deaths. The timeframe and causal attribution for these figures are not reported in the registry record. They should not be substituted for the primary serious adverse event count or interpreted as treatment-related deaths. No confidence interval or comparative safety analysis is reported.

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

The result does mean that the registry records serious adverse events in 11 of 22 participants at risk within the primary endpoint’s first 4 months of treatment. It also means that the study’s safety outcome is framed around a defined category of serious events, rather than every symptom or medical occurrence. The listed event terms provide additional descriptive information, but the record does not explain whether terms overlap within participants or provide details about individual event courses.

The result does not show that ipilimumab with palliative radiation therapy caused the recorded events. The primary outcome counts events observed during treatment; the registry summary does not report causal attribution. The result also does not establish how this experience compares with another treatment, because the trial is single-group and has no recorded randomized comparator. It cannot isolate the effects of ipilimumab from those of radiation therapy or other influences.

The safety count does not establish efficacy. Response rate, overall survival, response durations, stable disease, time to response, and progression-free survival are listed as secondary outcomes, but their analyses are not reported in the registry record. No efficacy conclusion can be drawn from the trial’s title, stated objective, or the presence of those outcomes in the registry.

The count is not accompanied by a confidence interval or statistical test in the registry record. Its precision and the degree to which it might generalize beyond the study group therefore cannot be quantified from the posted result. The separate adverse-event information includes other-event and death counts, but their timeframe and relation to treatment are not specified in the summary. These figures should be read as recorded descriptive information, not as evidence of causation.

Overall, the record documents a safety observation from a completed pilot study. It does not support a comparative treatment effect, a causal conclusion, or a broad claim about the expected outcome for people outside the study. Those questions require information and analyses not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how to read a safety count from a single-group trial. A count can convey what was recorded among the participants at risk and within a stated observation window. Here, the registry provides a defined serious adverse event endpoint and a count for the first 4 months of treatment. Such specificity is useful, but it does not remove the need to consider design and uncertainty.

The single-group design places a clear boundary around interpretation. A descriptive safety result can characterize the observed group, while a comparison requires a reference group and an analysis that supports a treatment contrast. Without those features, the count cannot distinguish treatment-related events from events that might arise from underlying illness or other circumstances. This is particularly important for a combination regimen, where the separate contributions of ipilimumab and radiation therapy cannot be identified from the group-level observation.

The record also illustrates why outcome availability and outcome results are different. It lists response and survival outcomes, but reports 0 analyses. Listing an outcome does not provide an estimate, a precision measure, or evidence about its direction. Similarly, a completed status does not by itself supply the missing statistical analyses.

Finally, the registry’s event terms and counts require careful reading. Seriousness, event frequency, attribution, and follow-up are distinct concepts. The record reports some of these elements, but not all: it defines serious events and gives the primary count, while causal attribution and confidence intervals are not reported. Keeping those distinctions explicit helps prevent a descriptive safety report from being mistaken for a comparative or causal result.

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 most important trial-specific limitation is the single-group design. Allocation is listed as NA, masking as NONE, and no control group is recorded. As a result, the safety observations cannot be contrasted with outcomes under another treatment strategy, and the separate effects of ipilimumab and radiation therapy cannot be distinguished.

The primary endpoint has a stated timeframe of 4 months, but the registry record does not report the follow-up duration for the other adverse-event and death counts. The summary also does not provide event-level details such as timing, recurrence, severity grading beyond the serious-event definition, or causal relationship. These omissions constrain interpretation of the safety profile.

Precision measures and analyses are absent from the registry record: it reports 0 analyses and provides no confidence interval or statistical test for the primary safety count. The registry does not report missing-data procedures, further analysis-population definitions, multiplicity handling, interim analyses, or the trial’s sample-size justification. It is therefore not possible to assess those aspects of the analysis from the record.

The secondary response and survival outcomes are listed, but their results are not reported. The recorded arm description also ends mid-phrase after describing the radiation schedule, so additional treatment-procedure detail is not available in that description. Together, these limitations mean the record supports a bounded description of the reported safety observations, not a complete evaluation of comparative safety or efficacy.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pilot Ipilimumab in Stage IV Melanoma Receiving Palliative Radiation Therapy — NCT01449279.
• Registry record last updated 2020-03-02; status last verified 2020-02.
• Results first posted 2017-03-10.
• 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

NCT01449279 is a completed phase 2, single-group trial sponsored by Stanford University, studying ipilimumab with palliative radiation therapy in stage IV melanoma. The registry lists enrollment as 22 and the primary outcome as serious adverse events during the first 4 months of treatment.

The posted primary result records 11 of 22 participants at risk as experiencing serious adverse events. The registry also lists event terms and separate counts for other adverse events and deaths. The design has no recorded comparator, and the record reports 0 analyses. It lists response and survival outcomes, but their results, confidence intervals, missing-data procedures, and causal attribution are not reported in the registry record. The safety result is therefore descriptive and does not establish comparative effects or efficacy.