Phase II Study of Ibrutinib in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study of Ibrutinib in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors (NCT02575300), a na phase 2 study. The primary outcome is Overall Radiographic Response Rate (ORR).

2. Clinical Question

The study’s stated purpose was to examine the good and bad effects of ibrutinib in advanced carcinoid tumors and pancreatic neuroendocrine tumors. Its primary endpoint counts participants meeting the study’s radiographic response definition. The record describes complete and partial response criteria, but it does not report how many participants met either criterion or the overall response rate.

The registry describes two disease cohorts, carcinoid tumors and pancreatic neuroendocrine tumors. Its brief summary says the study would enroll up to 51 participants, with 30 in the carcinoid cohort and 21 in the pancreatic neuroendocrine tumor cohort. The registry’s enrollment field reports 20. These are different types of record information: the former describes planned enrollment and the latter the reported enrollment. The record does not explain the difference or provide cohort-specific enrollment or response results.

Because there is no control group, the study can describe outcomes in participants who received ibrutinib, but cannot estimate a treatment contrast against an untreated or differently treated group. The registry record does not report an efficacy result that would answer even the descriptive response question.

3. Trial Design

This is a prospective phase II, open-label study of ibrutinib in advanced carcinoid tumors and pancreatic neuroendocrine tumors. The registry lists the study as completed. Its recorded start date is 2015-10-09, and its primary completion date is 2019-03-26. The sponsor is H. Lee Moffitt Cancer Center and Research Institute.

The design is single-group, and allocation is listed as not applicable. Masking is listed as none. Participants received ibrutinib; the arm description specifies an initial oral dose of 560 mg once daily. Since there is no separate control arm, the design does not provide a randomized, like-for-like comparison between ibrutinib and another treatment or control condition.

The brief summary describes two cohorts: carcinoid tumors and pancreatic neuroendocrine tumors. It says the study would enroll up to 51 participants, with 30 in the carcinoid cohort and 21 in the pancreatic neuroendocrine tumor cohort, and describes the cohorts as stratified equally. The registry’s enrollment field, however, reports 20. The record does not explain this difference, report the number enrolled in each cohort, or say whether the planned cohort targets were reached. It also does not clarify how the description of equal stratification relates to the stated cohort targets.

The primary outcome is overall radiographic response rate, assessed using RECIST v1.1, with a timeframe of up to 18 months. Secondary outcomes listed in the registry are progression-free survival, overall survival, occurrence of possibly related adverse events, and duration of response. The record lists five outcome measures, but it does not provide results for the primary endpoint or the secondary outcomes. No statistical analyses are reported in the registry record.

The design and enrollment information describe the study’s intended structure and recorded completion status, not the magnitude or certainty of any treatment effect. Without a reported response count, an estimated response rate, or a control group, the registry record does not support a quantitative estimate of comparative efficacy.

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

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one dose of study drug.

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 Overall Radiographic Response Rate (ORR), measured over Up to 18 months.

The primary endpoint is overall radiographic response rate. It counts participants who meet the study’s response criteria, rather than measuring a continuous change averaged across all participants. The endpoint is defined using RECIST v1.1. The record describes measurable disease as at least one measurable lesion and specifies complete response as disappearance of all target lesions, confirmed by repeat assessment no less than 4 weeks after response criteria are first met. Partial response requires at least a 30% decrease in the sum of target-lesion diameters from the baseline sum.

Radiographic response is used in oncology studies to classify changes in measurable tumors according to prespecified imaging criteria. A standard definition makes response categories more explicit and can support consistent assessment across participants and time. Complete and partial responses are different categories, although both contribute to an overall response measure when the study’s analysis defines them as responses.

The registry says this endpoint applies to participants who received at least one dose of study drug and gives a timeframe of up to 18 months. It does not report the number assessed, the number with complete or partial response, the number with no response, or the calculated overall response rate. It also does not report details of imaging review procedures or how missing or unevaluable assessments were handled. Therefore, the endpoint definition is available, but its observed value and the precision of that value are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how an endpoint is turned into an estimate, how uncertainty is described, and what conclusions the design can support. The registry record gives an endpoint definition and some study-design details, but it does not report the statistical analysis methods used for the primary outcome. The concepts below explain how such methods are generally interpreted; they are not claims about methods used in this study.

What does a response rate estimate?

For a binary endpoint such as response, each participant is classified according to whether the prespecified response criterion was met. The response rate is the proportion of participants in the analysis population who meet that criterion. For this study, the registry identifies the primary outcome as a count of participants and defines response using RECIST v1.1. The analysis population is described as participants who received at least one dose. The record does not report the response count, the denominator used in the analysis, or the resulting rate, so none of those quantities can be interpreted from the posted results.

A response rate is a descriptive summary of the observed group. It does not, by itself, show what would have happened to the same participants under a different treatment. That distinction is especially important in a single-group study. Without a control group, there is no direct randomized estimate of a difference between treatment groups, and changes in outcomes cannot be separated from other influences by a concurrent comparison.

What would a confidence interval add?

In general, a confidence interval describes statistical uncertainty around an estimated quantity under the assumptions of the method used. For a response rate, it would indicate a range of values compatible with the observed data and method, rather than a single point estimate alone. A wider interval indicates less precision; a narrower interval indicates greater precision. An interval does not correct design limitations, establish causation, or account automatically for bias or missing observations.

No confidence interval for the primary response rate is reported in the registry record. Since the response count and analysis denominator are also absent, the precision of the primary estimate cannot be assessed. The record does not state whether any interval was calculated or which method would have been used.

How does the design affect interpretation?

Random allocation, when used, helps make comparison groups similar on average with respect to measured and unmeasured characteristics. This study has no randomized comparison: allocation is listed as not applicable and the design as single-group. Consequently, a response outcome could describe the treated cohort, but the design does not estimate a randomized contrast. Open-label status means masking is listed as none; the record does not describe whether imaging assessments were independently reviewed or otherwise protected from knowledge of treatment.

The study describes two disease cohorts, but the registry does not report cohort-specific analysis methods or results. The brief summary states planned enrollment of up to 51, including 30 with carcinoid tumors and 21 with pancreatic neuroendocrine tumors, while the enrollment field reports 20. The record does not explain this difference. It also does not report whether the primary outcome was analyzed separately by cohort, pooled across cohorts, or in another way.

What do missing analysis details mean?

For binary outcomes, an analysis should define who is included in the denominator and how participants without an evaluable assessment are treated. Excluding participants without outcome data can change the set being described; counting them as nonresponders answers a different question. General statistical practice therefore distinguishes the intended analysis population from the participants with observed endpoint data. The registry defines the primary population as participants who received at least one dose, but does not report how many met that definition, how many had evaluable imaging, or how missing assessments were handled.

The registry record lists no statistical analyses. It does not report hypothesis tests, an analysis plan, adjustment for covariates, interim analyses, or a multiplicity approach. No conclusion should be drawn about whether these procedures were planned or performed. Their status is not reported in the registry record.

Why do safety counts need context?

Adverse event counts describe reported events or participants with events, depending on the endpoint definition. The record identifies the relevant event information as participant counts and reports serious and other adverse event counts, along with deaths and selected serious event terms. In general, counts do not alone explain how long participants were followed, whether events began before or after treatment, how events were attributed, or whether one participant experienced multiple types of event. Those details affect interpretation and are not reported in the registry record.

In general, sparse event counts can be imprecise, and the absence of a control group limits attribution of observed events to treatment. A serious adverse event and an event considered possibly related to treatment are not necessarily the same category. The registry lists possibly related adverse events as a secondary outcome but does not report a detailed result for that outcome. The posted safety counts should therefore be read as the information recorded, not as a comparative safety estimate.

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("Ibrutinib Therapy")
n      <- c(20)
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  Ibrutinib Therapy  20  0  0.0  0.0  16.8  0.0  16.1  0.1  16.1

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists overall radiographic response rate as the primary outcome and names progression-free survival, overall survival, occurrence of possibly related adverse events, and duration of response as secondary outcomes. It does not report a statistical analysis plan, hypothesis tests, or an approach to multiplicity. Multiplicity refers generally to the interpretive challenge created when multiple outcomes or comparisons are examined: the more questions asked, the greater the chance that an apparently notable finding may arise by chance. Whether and how this issue was addressed is not reported in the registry record.

The record gives a primary endpoint population of participants who received at least one dose of study drug. It does not state how participants without an evaluable radiographic assessment were handled, whether any participants were excluded from the analysis, or how missing data were treated. It also does not report the number with evaluable primary outcome data. These omissions mean the denominator for any response calculation cannot be confirmed from the registry record.

The registry reports enrollment of 20, while the brief summary describes a planned enrollment of up to 51 across the two cohorts. It does not explain the difference or state whether the study stopped enrolling early. Nor does it report cohort-specific enrollment or whether primary analyses pooled the cohorts. As a result, the extent to which the recorded enrollment corresponds to the planned populations is unclear.

No interim analysis details are reported, and no statistical analysis results are listed. This absence should not be interpreted as evidence that a particular method was or was not used outside the registry record. The record does not say how many participants were included in analyses of the secondary outcomes or how censoring and incomplete follow-up were handled for time-to-event outcomes.

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: abdominal pain (5.0%), small intestinal obstruction (5.0%), back pain (5.0%), generalized muscle weakness (5.0%).

The registry reports 2 participants with serious adverse events among 20 at risk and 20 participants with other adverse events among 20 at risk in the ibrutinib group. It also records 9 deaths. These are reported counts, not comparative estimates: the study has no control group. The registry does not report the timing of events, the duration of observation for each participant, or the relationship of each event to study treatment.

Four serious adverse event terms are listed: abdominal pain, small intestinal obstruction, back pain, and generalized muscle weakness. Each is reported at 5.0%. The record does not say whether these terms occurred in separate participants or whether participants could contribute to more than one term. The term-specific percentages should therefore be read as the registry reports them, without inferring additional participant counts or totals.

The secondary outcome list includes occurrence of possibly related adverse events, but the record does not provide a detailed result for that outcome. Seriousness and relatedness are distinct concepts: an event’s seriousness does not by itself establish that it was caused by treatment. The posted figures do not establish causation, comparative risk, or the completeness of event reporting.

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

The registry record describes a completed, open-label, single-group phase II study of ibrutinib in adults with advanced carcinoid tumors or pancreatic neuroendocrine tumors. It specifies an overall radiographic response endpoint defined using RECIST v1.1 and gives a primary outcome timeframe of up to 18 months. It also reports selected adverse event counts. These details clarify what the study was intended to assess and what safety information is recorded.

The record does not report the primary response count or rate. It therefore does not show how many participants met the complete or partial response criteria, how precise an estimated response rate would be, or how responses differed between the two disease cohorts. No secondary outcome results or statistical analyses are reported. A completed study status does not replace these missing outcome results.

Even if an observed response rate were reported, this single-group design would describe outcomes among participants receiving ibrutinib rather than establish a comparative effect against another treatment. The absence of a control group means that the registry record cannot show whether outcomes differ from what would have occurred under an alternative approach. The record also does not provide enough information to assess the role of missing or unevaluable outcome data.

The enrollment field reports 20, while the brief summary describes a plan for up to 51 participants across two cohorts. The registry does not explain that difference or report cohort-specific enrollment. The safety counts are likewise limited: they do not provide a control comparison, detailed event timing, or a complete account of attribution. They should not be used alone to infer that ibrutinib caused an event or changed the risk of an event.

Accordingly, the posted information documents the study design, endpoint definition, planned cohort structure, enrollment as recorded, and selected safety counts. It does not provide the efficacy result needed to answer the primary response question, nor does it establish a comparative treatment benefit or harm.

14. Why This Trial Matters Statistically

This study illustrates how a trial record can specify a clinically meaningful outcome while leaving the result needed to interpret that outcome unreported. The primary endpoint is overall radiographic response rate, with a stated RECIST v1.1 definition and a defined primary population. Those details make the intended measurement clearer, but without the response count, denominator, and uncertainty estimate, the endpoint cannot be quantified from the registry record.

The single-group structure also sets an important limit on statistical interpretation. A response rate in a treated cohort can be descriptive, but it is not a randomized comparison. This distinction matters when readers consider whether an outcome can be attributed to treatment rather than to other features of the participants, their disease, or their care. The design details alone cannot resolve that question.

The record also shows why planned enrollment and recorded enrollment should not be conflated. The brief summary describes a plan for up to 51 participants distributed across two disease cohorts, whereas the registry enrollment field reports 20. Because no explanation or cohort-specific counts are given, the scope of the completed study relative to its stated plan is uncertain from the registry record.

Finally, safety counts require the same attention to definitions and context as efficacy outcomes. Serious adverse event counts, other adverse event counts, deaths, and term-specific percentages answer different descriptive questions. Without details about timing, overlap, attribution, follow-up, and a comparison group, they do not provide a comparative estimate of risk. The statistical lesson is that endpoint definitions, analysis populations, denominators, uncertainty, and study design all shape what a reported number can mean—and missing results can prevent even a well-defined endpoint from being interpreted quantitatively.

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 primary limitation for interpreting this record is that it does not report the primary outcome result. Although the endpoint is defined as overall radiographic response rate using RECIST v1.1, the record gives no response count, rate, confidence interval, or hypothesis test. The listed secondary outcomes also lack reported results. Statistical precision and the magnitude of any observed outcome therefore cannot be assessed from the registry record.

The single-group, open-label design offers no randomized control comparison. It can describe outcomes in the treated group but cannot estimate a treatment contrast against a concurrent control. The record does not state whether imaging assessments were reviewed by assessors unaware of treatment or whether any other safeguards were used to limit assessment bias.

Enrollment information is not fully reconciled. The registry reports enrollment of 20, while the study summary describes planned enrollment of up to 51, with 30 participants in the carcinoid cohort and 21 in the pancreatic neuroendocrine tumor cohort. The reason for the difference, cohort-specific enrollment, and relationship between the enrollment field and the endpoint analysis population are not reported. The number who received at least one dose or had evaluable imaging is also not reported.

The registry does not report missing-data handling, outcome-analysis methods, multiplicity procedures, interim analyses, or a statistical analysis plan. For safety, it reports selected counts and event terms but not detailed timing, follow-up, attribution, or overlap. These limitations leave important questions about the denominator, assessment process, and interpretation unresolved; they do not establish that a particular procedure was or was not undertaken outside the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Study of Ibrutinib in Advanced Carcinoid and Pancreatic Neuroendocrine Tumors — NCT02575300.
• Registry record last updated 2020-09-11; status last verified 2020-09.
• Results first posted 2019-10-02.
• 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 completed, prospective, open-label phase II single-group study of ibrutinib in advanced carcinoid tumors and pancreatic neuroendocrine tumors. The intervention is listed as an initial oral dose of 560 mg once daily. The primary endpoint is overall radiographic response rate under RECIST v1.1, with assessment planned up to 18 months, among participants who received at least one dose.

The brief summary describes two cohorts and planned enrollment of up to 51 participants, while the enrollment field reports 20. The record does not explain the difference. It reports selected safety counts, including 2 participants with serious adverse events among 20 at risk, 20 with other adverse events among 20 at risk, and 9 deaths. Four serious adverse event terms are each listed at 5.0%.

No primary response result, secondary outcome results, or statistical analyses are reported in the registry record. The single-group design provides no randomized control comparison, and the posted information does not establish a comparative treatment effect.