Study of Mutation-Targeted Therapy With Sunitinib or Everolimus in People With Advanced Low- or Intermediate-Grade Neuroendocrine Tumors of the Gastrointestinal Tract and Pancreas With or Without Cytoreductive Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Mutation-Targeted Therapy With Sunitinib or Everolimus in People With Advanced Low- or Intermediate-Grade Neuroendocrine Tumors of the Gastrointestinal Tract and Pancreas With or Without Cytoreductive Surgery (NCT02315625), a non-randomized phase 2 study. The primary outcome is Median Amount of Time Subject Survives Without Disease Progression After Treatment.

2. Clinical Question

The study asks whether drug selection based on a tumor’s defective gene is associated with tumor response and progression-free time in this clinical setting. Its primary outcome is a median time-to-event measure, rather than a direct comparison of average tumor size or a count of responses. The record also lists overall response, overall survival, median survival time, and serious and non-serious adverse events as secondary outcomes.

The treatment question is exploratory in important ways. The trial is phase II, non-randomized, unmasked, and registered as a crossover model. The record does not explain how mutation results mapped to treatment choices, how treatment sequences were assigned, or which participants crossed over. Thus, the record establishes the intended clinical question and named treatments, but does not support treating the groups as randomized alternatives or attributing differences to the drug alone.

3. Trial Design

This is a phase II study with non-randomized allocation, no masking, and a crossover model. The registry lists sunitinib and everolimus as the two treatments. Enrollment is 16. The study status is terminated; the reason for termination is not reported in the registry record. The listed start date is 2015-04-08, and the primary completion date is 2019-05-22.

The brief summary describes screening with medical history, physical examination, scans, and laboratory tests. The study team assessed whether a participant should undergo surgery. For participants proceeding to surgery, a tumor sample was to be tested for mutation type; participants not proceeding to surgery were also to have a small tumor sample removed for testing. The summary says participants thought potentially curable by surgery would leave the study, while other participants would be assigned to sunitinib or everolimus.

The intervention descriptions specify the drugs, and the brief summary describes oral daily dosing. However, dose, treatment duration, detailed eligibility criteria, and the rules governing mutation-based treatment assignment are not reported in the registry record. Although the registered model is crossover, the sequence, timing, and conditions for any crossover are also not reported. These missing details limit reconstruction of how participants moved through the study and how exposure to each treatment was defined.

The primary outcome is median time without disease progression after treatment, with a timeframe of up to approximately 2 years. The record says the data for this outcome are reported per sequence as prespecified in the protocol, but does not provide the actual sequence-level median results. The registry also lists secondary outcomes, but no outcome analyses are reported. As a result, the design and intended measurements can be described, while the treatment results and detailed analysis procedures cannot be evaluated from this 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.

Before assignment: Study closed due to poor accrual.

First Intervention

Reasons for not completing this period:

Second Intervention

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The data in this outcome measure is reported per sequence as pre-specified in the protocol.

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 Median Amount of Time Subject Survives Without Disease Progression After Treatment, measured over Up to approximately 2 years.

The primary endpoint is the median amount of time a participant survives without disease progression after treatment. It is a time-to-event measure: the event is disease progression, and the outcome summarizes the point at which half of the relevant observations have experienced progression or have otherwise reached the endpoint definition. The timeframe is up to approximately 2 years. The registry says results are reported per sequence as prespecified in the protocol, but it does not report the median value or its full range.

Progression was assessed using RECIST. The registry defines it as at least a 20% increase in the sum of target-lesion diameters, relative to the smallest sum recorded on study, including baseline if that was the smallest. The sum must also increase by at least 5 mm in absolute terms. The appearance of one or more new lesions also qualifies as progression. This definition combines change in measured lesions with the appearance of new lesions.

General statistical context: time-to-event endpoints retain information about when an event occurs, rather than reducing follow-up to whether an event was observed. A median can be useful when follow-up times differ or when a distribution is not well described by an average. It does not, on its own, describe the uncertainty around the estimate, the full time course, or the comparison between treatments. Those interpretations require results and methods that are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: a clinical trial’s design determines which comparisons its data can support. Random allocation tends to balance known and unknown prognostic factors across treatment groups, on average. In a non-randomized study, treatment selection may be associated with patient characteristics or clinical decisions. An observed group difference can then reflect treatment, those differences in participants, or both. This study is explicitly non-randomized, and its record cautions that the arms are not a like-for-like control comparison. The record does not report an adjustment method to address confounding.

What does a median time-to-event result describe?

General statistical context: a time-to-event analysis considers both whether an event occurred and the time until it occurred. The median is a point in the event-time distribution, not an estimate of the average time and not a measure of treatment effect by itself. A median should be interpreted with information about uncertainty and follow-up. For example, a confidence interval expresses a range of values compatible with the data and the statistical method, while a range of observed times describes the spread of observations. Those quantities answer different questions. The registry identifies full range as the dispersion measure for the primary outcome, but it does not report the median or range values.

Time-to-event methods can also account for observations whose event time is not known because follow-up ends before the event is observed. General statistical context: such observations are often described as censored. Whether and how censoring was handled, what rules defined follow-up, and whether a survival curve or other estimator was used are not reported in the registry record. It would not be appropriate to infer those methods from the endpoint name alone.

How should the progression definition be read?

The registry defines progression using RECIST: at least a 20% increase in the sum of target-lesion diameters from the smallest sum on study, with an absolute increase of at least 5 mm, or the appearance of one or more new lesions. This definition makes the event clinically and analytically specific: the endpoint depends on lesion measurements and new-lesion assessment, not simply on a general clinical judgment of worsening. The record does not report details such as review procedures, assessor masking, or how missing scans were handled.

What does the crossover model imply?

General statistical context: crossover designs expose a participant to treatments in an order, so treatment sequence and prior exposure can matter. Interpretation may depend on the washout period, carryover effects, period effects, and the conditions under which a participant can move to another treatment. These are general design considerations, not claims about what occurred in this study. The registry lists the model as crossover and says the primary outcome is reported per sequence as prespecified. The sequence schedule, switching rules, washout procedures, and any analysis of carryover or period effects are not reported in the registry record.

The registry’s crossover designation should not be confused with randomization. Allocation is listed as non-randomized. The record does not explain whether sequence assignment was determined by mutation findings, clinical judgment, or another rule. Without this information and without reported outcome analyses, it is not possible to assess the comparability of sequences or estimate a treatment contrast.

What can be said about precision and power?

General statistical context: a confidence interval describes statistical uncertainty around an estimate; a narrower interval indicates greater precision under the chosen model. A small amount of information often yields imprecise estimates, but precision depends on the observed event pattern, follow-up, and analysis as well as enrollment. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be evaluated.

Planning sample sizes are different from observed results. They describe how many participants or events a hypothetical study might need under stated assumptions to target a chosen power and significance level. The record notes planning assumptions based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; time-to-event illustrations are defined in terms of total events. These are planning illustrations, not observed power and not evidence that the study achieved a particular level of power. The record does not report the trial’s own sample-size justification. No sample-size illustration values are stated in the registry entries summarized for this analysis.

General statistical context: power is a design probability tied to an assumed effect and analysis, not a retrospective probability that a study’s conclusion is correct. A non-significant result, if one were reported, would not by itself establish no effect; interpretation would require the estimate, uncertainty, design, and analysis details. Here, no inferential outcome results are reported, so there is no basis for discussing statistical significance or an observed treatment effect.

Which analysis details are unavailable?

The registry record does not report a statistical analysis plan, the primary analysis population, the handling of missing outcome data, or the approach to multiple outcomes. It does not report whether covariates were adjusted for, how treatment sequence was modeled, or whether analyses were planned by mutation type. These details matter because analytical choices can alter estimates and their uncertainty, particularly in a non-randomized study with a crossover structure.

General statistical context: over-dispersion occurs when variability is greater than a statistical model expects, which can make standard errors too small if ignored. It is a consideration for some count outcomes, but the registry record does not describe a count model or an over-dispersion assessment for this trial. It should not be assumed that such a method was used or required for the reported endpoint. In this study record, the primary endpoint is time-to-event and no analysis result is posted.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcomes in addition to the primary progression-free time measure: overall response, overall survival, median survival time, and serious and non-serious adverse events. Examining multiple outcomes can increase the chance of finding at least one apparently notable result by chance. General statistical context: multiplicity procedures can control or describe that risk, but their choice depends on the prespecified analysis plan and the role of each outcome. The registry record does not report a multiplicity strategy, hierarchy among secondary outcomes, or any outcome analyses.

The primary endpoint is stated as median time without disease progression after treatment, with the data reported per sequence as prespecified in the protocol. However, the protocol’s statistical details are not reported in the registry record. The record does not describe which participants were included in the primary analysis, whether all enrolled participants were analyzed according to an assigned treatment, or whether a different population was used. It also does not describe how treatment discontinuation, crossover, or incomplete follow-up affected analysis populations.

Missing-data methods are not reported. For a time-to-event outcome, key information would include how participants with no documented progression by the end of follow-up were handled and how incomplete assessment was treated. The registry’s endpoint timeframe is up to approximately 2 years, but the actual follow-up distribution and missing assessment counts are not reported. No assumptions about these matters can be made from the endpoint definition alone.

The record also does not report interim analyses, stopping boundaries, or a missing-data sensitivity analysis. The study status is terminated, but the reason for termination and any relationship to interim findings are not reported in the registry record. Without an analysis plan and results, it is not possible to determine how multiplicity, missingness, or analysis populations affected the conclusions.

11. 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: anemia (9.1%), duodenal ulcer (9.1%), hypercalcemia (9.1%), neoplasms benign, malignant and unspecified (incl cysts and polyps) - other, multiple myeloma (9.1%), sepsis (9.1%).

The registry reports serious and non-serious adverse event counts separately for sunitinib and everolimus. In the sunitinib group, 3 participants among 15 at risk had serious adverse events, and 14 among 15 had non-serious adverse events. In the everolimus group, 2 participants among 11 at risk had serious adverse events, and 7 among 11 had non-serious adverse events. One death is listed in each group.

These figures are descriptive. The study was non-randomized, and the registry cautions that the arms are not a like-for-like control comparison. The counts should not be interpreted as a causal comparison of treatment safety. The record does not state whether the events or deaths were judged related to treatment, or provide detail about event timing, duration, severity grading, or recurrence.

The most frequently listed serious event terms each have a reported frequency of 9.1%: anemia, duodenal ulcer, hypercalcemia, multiple myeloma under the broader neoplasm category, sepsis, and acute kidney injury. The record does not explain whether the listed terms refer to unique participants or overlapping events. The counts and terms are not a complete clinical narrative and do not establish the likelihood of an event for a particular person.

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

The record establishes that a phase II study examined mutation-targeted sunitinib or everolimus in people with advanced low- or intermediate-grade neuroendocrine tumors of the gastrointestinal tract and pancreas, with or without cytoreductive surgery. It also defines the primary endpoint as median time without progression and specifies the RECIST criteria used to identify progression. Those details clarify the clinical question and the outcome the study intended to measure.

The record does not report the primary outcome estimate or any outcome analyses. It therefore cannot show how long participants remained free of progression, how precise such an estimate was, or whether outcomes differed by treatment sequence. The secondary outcomes are listed, but their results are not reported in the registry record. The available information cannot support a claim that either drug improved outcomes, or that one was superior to the other.

The design also limits causal interpretation. Allocation was non-randomized, there was no masking, and the study was registered as a crossover. The record does not give enough detail to determine treatment selection, sequence assignment, or handling of crossover. Any observed group difference, if reported elsewhere, would need interpretation in light of possible differences between participants and treatment sequences. The registry itself notes that the treatment arms are not a like-for-like control comparison.

The adverse event information documents reported counts, terms, and deaths by group. These data do not by themselves establish treatment attribution or comparative risk. The status is terminated, but the reason is not reported. The result is therefore a record of study intent, design features, and some safety reporting, rather than a complete account of effectiveness or safety.

General statistical context: a trial result is most informative when its estimate, uncertainty, analysis population, and design limitations can be considered together. Here, several of those elements are absent. The absence of a reported result is not evidence that there was no effect; it means the registry record does not permit an effect estimate or a conclusion about the primary question.

13. Why This Trial Matters Statistically

This study illustrates why trial design and analysis details matter alongside the name of an outcome. A median time-to-event endpoint can summarize when progression occurs, but interpretation also depends on follow-up, censoring, event assessment, and the precision of the estimate. Although the registry defines progression carefully using RECIST, it does not report the median or uncertainty around it. Readers can identify what the study intended to measure, but not the magnitude or precision of the result.

It also highlights the difference between a treatment comparison and a randomized treatment contrast. This study is non-randomized, and the registry explicitly warns that the groups are not like-for-like controls. That distinction matters when interpreting any apparent difference: treatment assignment may be connected to participant characteristics, mutation findings, or clinical decisions. The registry does not describe enough of the assignment process to assess those possibilities.

The crossover designation raises additional questions about sequence, treatment order, and prior exposure. The record says the primary endpoint was reported per sequence but gives no sequence-level outcomes or analysis details. A registered design label alone does not reveal how the actual study handled switching, follow-up, or treatment carryover.

Finally, this record separates study intent from available evidence. It contains a stated clinical question, outcome definitions, and safety counts, while reporting no outcome analyses. The study status is terminated, but no reason is recorded. Recognizing these gaps prevents design features and descriptive safety data from being mistaken for evidence of a treatment effect. The record is useful for understanding the intended approach, while its missing results and methods constrain what can be concluded.

14. 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 key limitation is that the registry record does not report the primary outcome result or any outcome analyses. There is no median progression-free time, full range, confidence interval, or treatment-effect estimate to interpret. The secondary outcomes are named but their results are also not reported. Consequently, the posted information cannot establish an efficacy result or quantify its uncertainty.

The study enrolled 16 and used non-randomized allocation. The registry cautions that the arms are not a like-for-like control comparison. The criteria connecting mutation results to treatment assignment are not reported, so potential differences between groups cannot be assessed. No adjustment strategy is described. The lack of masking may also matter for assessments or reporting, but the registry does not describe assessor procedures.

Although the model is registered as crossover, sequence details, switching rules, and handling of prior treatment are not reported. This limits understanding of exposure and of how the per-sequence primary outcome was analyzed. The record also lacks the statistical analysis plan, the analysis population, missing-data procedures, multiplicity handling, and the trial’s own sample-size justification.

The study is listed as terminated, with no termination reason reported. The timeframe for the primary endpoint is up to approximately 2 years, but actual follow-up and the completeness of outcome assessment are not reported. Safety counts are descriptive, and the record does not establish attribution to treatment or provide detailed event context. Together, these limitations mean that the registry record supports description of the study’s intended design and recorded safety information, but not a reliable comparative conclusion about treatment outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Mutation-Targeted Therapy With Sunitinib or Everolimus in People With Advanced Low- or Intermediate-Grade Neuroendocrine Tumors of the Gastrointestinal Tract and Pancreas With or Without Cytoreductive Surgery — NCT02315625.
• Registry record last updated 2020-09-09; status last verified 2020-08.
• Results first posted 2020-09-09.
• 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.

18. Record Summary

This phase II study evaluated mutation-targeted sunitinib or everolimus for advanced low- or intermediate-grade neuroendocrine tumors of the gastrointestinal tract and pancreas, with or without cytoreductive surgery. It was non-randomized, unmasked, and registered as a crossover study, with enrollment of 16. The study is listed as terminated.

The primary endpoint was median time without disease progression after treatment, assessed using RECIST and with a timeframe of up to approximately 2 years. The registry record does not report the primary outcome result or any outcome analyses. It also does not report the reason for termination, detailed treatment sequence, analysis plan, missing-data methods, or analysis populations.

Safety information includes serious and non-serious adverse event counts and one death listed in each treatment group. These descriptive data do not establish treatment attribution or a causal comparison. The record supports a description of the study’s design and intended measures, but not conclusions about comparative efficacy or safety.