Fosaprepitant for N/V With High-dose Interleukin-2 for Metastatic Melanoma and Renal Cell Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Fosaprepitant for N/V With High-dose Interleukin-2 for Metastatic Melanoma and Renal Cell Carcinoma (NCT01874119), a randomized phase 2 study. The primary outcome is Number of Patients With Complete Response During Inpatient Admission.

2. Clinical Question

The clinical question concerns prevention of vomiting in a specific treatment setting, rather than treatment of nausea and vomiting across all chemotherapy settings. The crossover design means the same participant could experience both study conditions during separate admissions. This can support a within-participant comparison when the outcome data and analysis account for the pairing. However, the registry’s posted results do not include an estimable two-arm comparison, and do not explain how the complete-response counts relate to the crossover periods.

The trial record identifies the study as Phase 2 and randomized. Its title describes a double-blind placebo-controlled crossover study, while the registry classifies masking as triple. The brief summary says that participants and the study doctor would not know which admission involved fosaprepitant or placebo. The identity of any additional masked role is not reported in the registry record. The study status is terminated. The record gives no explanation for termination.

3. Trial Design

This was a randomized Phase 2 crossover study of intravenous fosaprepitant and saline placebo during high-dose interleukin-2 treatment. Its official title describes a Phase 2B double-blind placebo-controlled study. The registry classifies allocation as randomized, masking as triple, and the model as crossover. The brief summary describes participants receiving fosaprepitant during either the first or second hospital admission and placebo during the other. The treatment descriptions specify dosing every 48 hours during a 6-day admission for both study conditions.

The crossover structure differs from a design in which separate groups receive only one treatment. In a crossover, observations from the same participant under both conditions may be related. A statistical comparison generally needs to preserve that pairing rather than treating all treatment observations as independent. The registry does not report the randomization sequence, the timing between admissions, any washout period, or whether treatment order was included in the analysis. It also does not report how period effects or changes in a participant’s condition across admissions were handled.

The registry reports enrollment of 13 participants. For the primary outcome, it lists 7.0 participants and a count of 1.0 in the fosaprepitant arm, and 7.0 participants and a count of 0.0 in the placebo arm. Because this is a crossover study, these arm entries need not represent distinct groups of participants. The relationship between the enrollment figure and the arm-level entries is not explained in the registry record, and the posted information does not identify the participant-level pairs.

The study status is terminated, and the primary completion date is 2015-12-03. The start date is 2013-09. The registry does not report why the study was terminated, whether all planned admissions were completed, or whether the termination affected the planned analysis. The intended population was people receiving high-dose interleukin-2 for metastatic melanoma or metastatic renal cell carcinoma. Detailed eligibility criteria, baseline characteristics, and the number of participants contributing to each period are not reported in the registry record.

The brief summary says the study was designed to limit potential bias through blinding. It describes participants and the study doctor as unaware of assignment at each admission. The registry’s triple-masking classification suggests an additional masked role, but that role is not identified. The record does not report whether blinding was assessed or whether the masking was maintained throughout the study.

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.

First Intervention (6 Days)

Washout (7 Days)

Second Intervention (6 Days)

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 Number of Patients With Complete Response During Inpatient Admission, measured over From the initiation of through 48 hours following the final dose of Interleukin-2.

The primary endpoint is the number of participants with a complete response during inpatient admission. The registry’s operational definition of complete response is no vomiting from the initiation of high-dose interleukin-2 through 48 hours following the final dose. It is therefore a binary participant-level outcome: a participant either meets the stated no-vomiting criterion or does not. The endpoint is not defined as a measure of nausea, vomiting severity, or use of rescue medication.

In general, a binary endpoint can translate a clinically relevant event into a count that is straightforward to interpret. Here, the outcome focuses on whether vomiting occurred over a specified treatment-related period. That makes the endpoint relevant to the trial’s stated aim of evaluating vomiting during high-dose interleukin-2 therapy, while leaving other aspects of nausea and vomiting outside the recorded definition.

The timing matters: the window begins with interleukin-2 initiation and ends 48 hours after the final dose. The record does not give more detail about how vomiting was assessed, how events were recorded, or how participants with incomplete observation during that window were handled. Those details are important for understanding the consistency of endpoint ascertainment, but are not reported in the registry record.

The registry lists a count of 1.0 for fosaprepitant and 0.0 for placebo, with 7.0 participants in each listed arm. Those counts alone do not show whether the same participants contributed to both treatment conditions or how outcomes were paired across admissions. The record does not post an estimable comparative analysis for this binary endpoint. Consequently, the counts should be read as descriptive entries rather than as a complete estimate of the treatment contrast.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a crossover design require?

In general, a crossover design lets participants receive more than one study condition, often in different periods. Because outcomes from one participant can be related across conditions, analysis ordinarily needs to account for the within-participant pairing. For a binary outcome, the paired pattern matters: an outcome under fosaprepitant can be compared with the outcome for the same participant under placebo. Marginal counts for each condition do not reveal that pattern. The registry identifies this study as crossover but does not post paired data or describe the method used to analyze paired outcomes.

Period and order can also matter in crossover studies. In general, outcomes might differ between admissions for reasons unrelated to assigned treatment, and the order of the conditions could be relevant. The record does not report the interval between admissions, any washout, treatment-order results, or methods for addressing period effects. These omissions do not show that such issues affected the trial; they mean the registry record does not let readers assess how they were handled.

What do the posted counts say?

The primary endpoint is a participant count, with complete response defined as no vomiting over the stated treatment window. The registry lists 1.0 participant with a response in the fosaprepitant arm and 0.0 in the placebo arm, with 7.0 participants in each. These counts are descriptive. The registry specifically indicates that values are missing or not estimable for a two-arm comparison of the binary endpoint. It therefore does not provide a comparative effect estimate or a test result that can be interpreted as a treatment comparison.

In general, a binary comparison can be expressed in different ways, such as a difference in event probabilities or a relative measure. Those measures answer related but distinct questions, and their uncertainty depends on the study design and the observed data. For a crossover study, a suitable comparison must also respect the pairing. No recalculated comparative result is appropriate from the posted summaries because the paired outcomes are not available. There is no sponsor analysis posted that could take precedence over a recalculation.

What would an uncertainty interval contribute?

In general, a confidence interval conveys the precision of an estimate by showing a range of values compatible with the data and the analysis assumptions. It is not a guarantee that the true value lies in that range, and its interpretation depends on the method used. No comparative confidence interval is reported for the primary endpoint. The registry therefore gives no direct measure of how precisely the treatment contrast is estimated.

When events are sparse, estimates can be sensitive to individual outcomes and to the method used. In a crossover analysis, the paired pattern can be especially important: participants whose outcome is the same in both periods contribute differently to a paired comparison than those whose outcome changes. The posted marginal counts do not show how many participants had concordant or discordant outcomes. Without that information, neither the estimated contrast nor its precision can be reconstructed from the record.

How should sample-size planning be understood?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, the analysis, and the desired statistical properties. It is not an observed result, and it does not measure the probability that a completed study has found a true effect. A planning illustration based on an observed effect is especially dependent on that effect estimate and should not be read as the trial’s original design justification.

The registry does not report a sample-size justification, a target enrollment, or the assumptions used by the investigators when planning the study. It also does not report a formal power calculation. Enrollment of 13 is reported, but enrollment alone cannot establish whether the study was adequately sized for its intended comparison. The analysis population and paired outcomes are also not described, limiting any assessment based on sample size.

What does the analysis record leave unknown?

The registry reports zero posted analyses and no posted secondary outcomes. It does not identify a statistical test, an estimand, a confidence-interval method, or an approach to missing observations. It does not state whether the primary analysis followed an intention-to-treat population, a per-protocol population, or another definition. Those details are needed to evaluate how participants and admissions were included and how deviations or incomplete outcome records were treated.

In general, statistical methods should match the design and the endpoint. For this trial, a method for a paired binary outcome would need to account for the crossover structure; an analysis treating the arm entries as independent groups might not preserve that relationship. The record does not identify the method used, and the primary comparative result is not estimable from the posted information. Accordingly, no test statistic, p-value, or confidence interval should be inferred from the raw counts.

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("Fosaprepitant", "Placebo")
n      <- c(7, 7)
events <- c(1, 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  Fosaprepitant  7  1  14.3  0.4  57.9  2.6  51.3  3.2  52.7
ARM  Placebo  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9

11. Multiplicity, Missing Data and Analysis Populations

The registry reports one primary outcome measure and zero posted secondary outcomes. It also reports zero posted analyses. The record does not describe a statistical analysis plan or specify whether multiple comparisons, interim looks, or outcome selection were addressed. The absence of those details means multiplicity procedures cannot be evaluated; it does not establish that any particular adjustment was or was not used.

In general, multiplicity arises when a study makes several statistical comparisons, because repeated testing can increase the chance of at least one apparently notable result. A prespecified primary endpoint and analysis can help clarify which result is central. Here, the endpoint is identified, but the comparative analysis and its statistical plan are not reported in the registry record. No interim analyses are reported, and their status is therefore unknown.

Missing-data handling is also not described. The registry does not state whether any endpoint observations were missing, how incomplete admissions were handled, or whether any imputation or sensitivity analysis was used. The 13 enrolled participants and the arm-level entries of 7.0 participants in each condition are not accompanied by a participant-flow account that explains who contributed data in each period. In a crossover study, that information matters because a missing outcome in either period can affect whether a paired comparison is available.

The analysis population is not defined. The record does not say whether all randomized participants were included, whether participants needed to complete both admissions, or whether any exclusions were applied. These gaps prevent readers from assessing the consequences of missing data or the scope of the analysis. They also prevent confirmation that the posted counts correspond to the full randomized population.

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: cardiac arrest (33.3%), sepsis (11.1%), autoimmune disorder - myocarditis (11.1%), hypoxia (11.1%), upper gi hemorrhage (9.1%).

The registry lists serious adverse events separately for the fosaprepitant and placebo groups. For fosaprepitant, 11 participants are listed as at risk and 3 as affected; for placebo, 9 are listed as at risk and 4 as affected. The registry also lists 2 deaths in each group. These are descriptive safety entries, not a comparative safety analysis. The record does not provide an adjusted comparison, uncertainty interval, or explanation of how participants were assigned to these safety denominators in a crossover study.

The registry lists serious-event terms with percentages, including cardiac arrest at 33.3%, sepsis at 11.1%, autoimmune disorder - myocarditis at 11.1%, hypoxia at 11.1%, upper GI hemorrhage at 9.1%, and other - uncal herniation at 9.1%. The denominator and calculation basis for these percentages are not reported in the registry record. They should not be interpreted as treatment-specific incidence estimates without that context.

The safety risk sets differ from the enrollment figure of 13, and the relationship between those entries is not explained. In a crossover study, participants may be exposed to both conditions, so group counts alone do not establish whether an event occurred during one treatment period or another. The registry does not report event timing, attribution, or a method for comparing safety across conditions. These figures describe the posted record but do not establish causation or comparative risk.

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

The trial addresses a focused question: whether intravenous fosaprepitant, compared with saline placebo, was associated with complete response during high-dose interleukin-2 admission, where complete response means no vomiting through 48 hours after the final dose. The registry reports one complete response in the fosaprepitant arm and none in the placebo arm, with 7.0 participants listed in each arm. These counts are the available primary-outcome summaries.

They do not, on their own, answer the comparative question. The trial used a crossover design, but the registry does not provide paired participant outcomes or an estimable two-arm analysis. A comparison that ignores pairing may not represent the design. Nor is a confidence interval reported to show the precision of any treatment contrast. Thus the posted counts cannot establish either the magnitude or the reliability of a difference between conditions.

The absence of an estimable comparison should not be interpreted as proof that the conditions were equivalent. It also should not be read as evidence that fosaprepitant did or did not alter vomiting outcomes. The record’s sparse results leave the primary comparative question unresolved. This is a statement about what the posted data can support, not a medical recommendation.

The endpoint has a specific scope. It records vomiting, not nausea, and the registry does not define complete response to include rescue medication use or other symptom measures. The results therefore do not address every component of chemotherapy-induced nausea and vomiting. The record also does not provide detailed participant characteristics, outcome-assessment procedures, or a complete account of missing observations, which limits judgments about how broadly the findings may apply.

Safety entries are similarly descriptive. Serious adverse event and death counts are posted, but the record does not establish attribution or provide a comparative analysis that accounts for crossover exposure. The status is terminated, with no reason for termination reported. Taken together, the registry supports a cautious description of the recorded counts and design, but not a firm conclusion about efficacy or comparative safety.

14. Why This Trial Matters Statistically

This trial is statistically notable because the crossover design and the endpoint both make the structure of the data important. A binary outcome such as whether a participant had any vomiting can be summarized as counts, but a crossover comparison also depends on how each participant’s outcomes relate across the two admissions. The registry’s arm-level counts do not reveal those paired outcomes. This illustrates why marginal summaries may be insufficient for interpreting a crossover result.

The record also shows the distinction between descriptive data and an estimable treatment comparison. Counts can be reported even when the registry does not provide a comparative estimate. Without a paired analysis and a measure of uncertainty, the posted counts do not quantify how large or precise a treatment contrast may be. This matters particularly when the number of enrolled participants is limited and the observed event counts are sparse.

Another statistical lesson is the need for clear participant flow and analysis populations. Enrollment is 13, while the primary outcome entries list 7.0 participants in each arm. The registry does not explain how these figures relate to periods, admissions, or unique participants. A clear account would help readers understand which observations contributed to the outcome analysis and whether incomplete crossover participation affected the comparison.

Finally, safety data require design-aware interpretation too. In a crossover trial, participants may experience both interventions, so group-level adverse-event counts need timing and attribution information to support a treatment comparison. The posted serious-event counts and terms are useful as a record of reported events, but without those details they cannot establish comparative safety. These issues are general lessons in interpreting trial registries: study design, analysis, participant flow, and uncertainty all shape what counts can mean.

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 limitation of the posted primary results is the absence of an estimable two-arm comparison for the binary endpoint. The registry gives arm-level counts but no paired outcome data, comparative estimate, confidence interval, or analysis method. Since the study is a crossover, the missing paired information is central to interpreting the primary result.

The record reports enrollment of 13 and lists 7.0 participants in each primary-outcome arm, but does not explain the relationship between these figures. It does not provide a participant-flow account, the number completing each admission, the number contributing outcomes in both periods, or reasons for any incomplete data. Analysis-population definitions and missing-data handling are not reported.

Trial conduct details are also limited. Randomized allocation and crossover design are recorded, but the randomization sequence, treatment order, timing between admissions, washout, and handling of period effects are not described. The registry classifies masking as triple, while the brief summary identifies the participant and study doctor as blinded; an additional masked role is not identified. The outcome-assessment procedures are not reported.

The study is terminated, but the record does not explain why. It does not report a sample-size justification, target enrollment, or statistical analysis plan. The record also lacks detailed baseline characteristics and does not explain how the serious-adverse-event denominators relate to crossover exposure. These gaps limit assessments of precision, applicability, safety comparisons, and potential bias. They do not show that any particular problem occurred, but they prevent readers from resolving these questions from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Fosaprepitant for N/V With High-dose Interleukin-2 for Metastatic Melanoma and Renal Cell Carcinoma — NCT01874119.
• Registry record last updated 2018-06-07; status last verified 2018-05.
• Results first posted 2018-05-04.
• 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

The registry describes a randomized Phase 2 crossover study of intravenous fosaprepitant versus intravenous saline placebo during high-dose interleukin-2 treatment for metastatic melanoma or metastatic renal cell carcinoma. It reports enrollment of 13 and a terminated status. The primary endpoint is the number of participants with no vomiting from interleukin-2 initiation through 48 hours after the final dose.

The posted primary counts are 1.0 of 7.0 for fosaprepitant and 0.0 of 7.0 for placebo. The registry does not provide an estimable two-arm comparison, paired outcome data, or an uncertainty interval. It reports serious adverse event counts and deaths by group, but does not explain attribution or the relationship of the safety denominators to crossover exposure. The reason for termination, sample-size justification, analysis plan, missing-data methods, and analysis population are not reported in the registry record.