Regorafenib in Patients With Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Regorafenib in Patients With Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma (NCT02098538), a na phase 2 study. The primary outcome is Number of Participants Alive With and Without Disease Progression.

2. Clinical Question

The clinical question concerns disease status after treatment with regorafenib in a group selected for progressive, recurrent or metastatic adenoid cystic carcinoma. The registry record names the primary outcome as the number of participants alive with and without disease progression at six months. Its description also refers to complete response, partial response and overall response, assessed using RECIST v1.0 criteria for target lesions and MRI.

This is a single-group question, not a comparison of regorafenib against a concurrent control treatment. The posted record therefore cannot directly estimate a treatment contrast against another arm. Any interpretation of the observed status would need to be understood in the context of the participants enrolled and the endpoint definitions used.

The registry record does not give numerical results for the primary endpoint. It does not report the count alive with progression, the count alive without progression, or the treatment of participants whose status could not be assessed at the endpoint. The information available therefore identifies what the study sought to measure, but not the observed primary outcome. Adverse-event summaries are reported separately and do not fill that gap.

3. Trial Design

The registry record describes a completed phase II, single-group study of regorafenib in patients with progressive, recurrent or metastatic adenoid cystic carcinoma. The recorded enrollment is 38. The sponsor is Memorial Sloan Kettering Cancer Center. The record lists the study start as 2014-03 and primary completion as 2024-11-07.

Because the study is single-group, all enrolled participants were assigned to the study’s regorafenib group rather than randomized between regorafenib and a concurrent control. Allocation is listed as not applicable, and masking is listed as none. Consequently, there is no randomized between-group comparison in this record. Changes in disease status or adverse events during the study cannot, by themselves, separate effects of treatment from other influences over time.

The brief study description says participants initially received a dose lower than the dose approved for other cancers, with an attempt to reduce the risk of side effects. It also says a physician could consider increasing the dose if a participant did well with the lower dose for at least a month on treatment. The record does not provide a detailed dose schedule, criteria for dose escalation, or the number of participants who received each dose.

The primary outcome is described as a participant count at six months, with disease status defined using RECIST v1.0 response criteria for target lesions assessed by MRI. A secondary outcome concerns participants evaluated for adverse events. The record lists three outcome measures but does not report numerical results for the primary endpoint. It does not report a detailed statistical analysis plan, the method for handling missing endpoint assessments, or the analysis population used for efficacy.

The status is recorded as completed. Completion indicates the registry’s status, but it does not by itself establish that all planned analyses or outcome reporting are present in the record. In particular, the posted information is not enough to reconstruct the primary endpoint findings or to assess how they were estimated.

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

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 Participants Alive With and Without Disease Progression, measured over 6 months.

The primary endpoint is titled “Number of Participants Alive With and Without Disease Progression,” with a timeframe of six months and the unit given as participants. In plain terms, it is a count-based description of participants’ disease status at the stated assessment time. Counts can communicate how many people fall into each reported status category, but their interpretation depends on clear category definitions and on knowing which participants were assessed.

The endpoint description refers to RECIST v1.0 for target lesions assessed by MRI. It defines complete response as disappearance of all target lesions, partial response as a >=30% decrease in the sum of the longest diameter of target lesions, and overall response as complete response plus partial response. These criteria offer a structured way to classify changes in measured lesions. Standardized definitions can make response assessments more consistent than an informal description of change.

The registry record does not explain how the response categories relate to the title’s distinction between alive with and without disease progression. Nor does it state how death before the assessment, a missing scan, or an unevaluable assessment was classified in the primary endpoint. Those details matter because a participant count is meaningful only when the categories and the population contributing to each count are clear.

No numerical primary endpoint results are reported in the registry record. As a result, the endpoint definition can be described, but the observed count in each disease-status category and the precision of those counts cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help turn study observations into estimates that answer a defined question. The method needs to match the design, outcome, and available data. In this study, the registry record describes a single-group phase II design and a participant-count primary endpoint at six months. It does not report the statistical analysis plan or primary endpoint results. The general explanations below therefore describe how such methods are usually interpreted, not methods confirmed to have been used for this study.

What does a participant count tell us?

In general, a count records how many participants meet a stated condition within a defined group and assessment period. A count alone does not indicate the proportion of the group unless the denominator is also stated. Nor does it express uncertainty around the estimate. For a count to be interpretable, the record should identify the population counted, the assessment time, the outcome categories, and how unavailable or unevaluable assessments were handled.

The primary endpoint title refers to participants alive with and without disease progression at six months. The description includes response criteria for complete response, partial response, and overall response, but the registry record does not provide numerical counts for the primary outcome. It also does not report how those response categories were incorporated into the alive-with-or-without-progression categories. Thus, the endpoint’s broad intent is visible, while essential details for reproducing its analysis are not reported in the registry record.

Why does the single-group design matter?

In general, a single-group study can describe outcomes among participants who received the study intervention. It cannot directly make a randomized comparison with an alternative intervention because there is no concurrent randomized control group. A change observed over time may reflect multiple influences, including the course of the condition, participant characteristics, assessment practices, and treatment. A comparison with external information would require additional assumptions and is not reported in the registry record.

Randomization is useful in comparative studies because it can balance measured and unmeasured participant characteristics across groups on average. That protection does not apply to a single-group design. The design can still provide descriptive evidence, but its estimates answer a narrower question: what outcomes were recorded in the enrolled group under the study conditions? They do not, by themselves, identify a causal treatment effect relative to another option.

What do confidence intervals and p-values mean?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under a specified model and procedure. A narrower interval indicates greater precision under those assumptions; a wider interval indicates less precision. A confidence interval does not account automatically for every possible source of bias, such as outcome misclassification or missing assessments. No confidence interval for the primary endpoint is reported in the registry record.

In general, a p-value describes how compatible data are with a specified null hypothesis under a statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. A p-value also does not correct for design limitations or unreported data. The registry record does not report a primary endpoint p-value or a test of a treatment contrast.

How should the planning illustration be read?

The record characterizes sample-size calculations as planning illustrations computed from an observed effect, rather than as the study’s own design. It describes assumptions of a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. The registry record does not report the fraction values in the registry record for this analysis, so those values cannot be described further.

In general, a sample-size illustration asks how many participants per arm might be needed under specified assumptions to detect a target effect with a chosen power. The answer depends on the assumed effect, variability or event rate, significance level, allocation, and statistical model. A planning calculation is conditional on those assumptions. It is not a measured result and does not show the probability that the completed study detected an effect. In particular, it must not be described as observed power.

The stated two-arm, equal-allocation assumptions do not match the recorded single-group design. They should therefore be treated as a hypothetical planning framework, not as a reconstruction of this trial’s design. The record does not report the trial’s sample-size justification, nor does it report the statistical plan that would connect any illustration to the study’s endpoint analysis.

What does over-dispersion mean in general?

For count outcomes, a statistical model may assume a particular relationship between the average count and its variability. Over-dispersion means the observed variability is greater than the model expects. If it is ignored, uncertainty estimates can be too small, which can make results appear more precise than warranted. Appropriate modeling depends on how the count was generated and whether it is a count of participants, events, or repeated events. The registry record describes the primary outcome as a count of participants; it does not report a model or an over-dispersion assessment.

These concepts clarify what information would be needed for a fuller statistical interpretation: the observed counts, analysis population, endpoint rules, uncertainty estimates, and analysis methods. The record does not report those primary efficacy details. General statistical principles cannot substitute for the missing study-specific results.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, comparisons, time points, or subgroup questions. In general, testing many questions can increase the chance of at least one apparently notable result even when no real effect exists. Statistical plans may address multiplicity through a prespecified hierarchy, adjusted significance thresholds, or an explicit decision to treat analyses as exploratory. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how multiple outcomes or analyses were handled.

The record lists a primary outcome and a secondary outcome concerning participants evaluated for adverse events, and it notes three outcome measures. It does not provide a detailed analysis plan identifying which outcomes were confirmatory, how results were to be compared, or whether any adjustment was planned. No p-values or primary endpoint estimates are reported in the registry record, so there is no set of efficacy tests available to assess for multiplicity.

Missing-data methods are also not reported in the registry record. For an endpoint assessed at six months, relevant details would include the number assessed, the number without an assessment, the reasons assessments were unavailable, and the rules used to classify participants with missing or unevaluable results. The record does not provide these details. The primary endpoint counts therefore cannot be interpreted as complete-case results, imputed results, or results under any other missing-data approach.

The analysis population is not reported in the registry record. It is not possible to determine whether the primary endpoint was intended to include all enrolled participants, participants who started treatment, or another defined group. The adverse-event risk group is reported as 38, but that does not establish the population used for efficacy. These gaps limit reproducibility and make it difficult to judge how exclusions or missing assessments may have affected the reported outcomes.

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: dyspnea (13.2%), rash, maculopapular (13.2%), lymphocyte count, decreased (10.5%), hypophosphatemia (7.9%), abdominal pain (5.3%).

The registry record lists 38 participants at risk for serious adverse events and reports 14 affected. It also lists 38 at risk for other adverse events and reports 38 affected. These are separate safety summaries; the record does not say that the categories are mutually exclusive. A participant may have experienced more than one type of event, so event terms should not be added together to infer a participant total.

The record separately reports 28 deaths. It does not state whether these deaths were considered adverse events, when they occurred, or whether they were attributed to study treatment, the cancer, or another cause. The count should be read as a registry-reported death total, not as a treatment-attributable count.

Among the listed serious adverse-event terms, dyspnea and rash, maculopapular are each reported at 13.2%; decreased lymphocyte count at 10.5%; hypophosphatemia at 7.9%; abdominal pain at 5.3%; and increased alanine aminotransferase at 5.3%. These percentages describe the entries as recorded. The registry record does not give counts for each term, event onset or duration, severity grades, or whether individual participants experienced multiple terms.

Safety summaries describe events recorded during a study; without a comparator and details of attribution, they do not establish that treatment caused an event or quantify an excess risk relative to another treatment. The posted information is not a complete clinical safety profile.

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

The record establishes that a phase II, single-group study of regorafenib in progressive, recurrent or metastatic adenoid cystic carcinoma was completed, with enrollment of 38 participants. It identifies a six-month primary endpoint concerned with the number of participants alive with and without disease progression and describes response criteria based on RECIST v1.0 and MRI. It also gives summary adverse-event counts and selected serious adverse-event terms.

The record does not report numerical primary endpoint results. It therefore does not show how many participants were alive with or without progression at six months, how many met the response criteria, or how precise any such estimate was. No efficacy estimate, confidence interval, or p-value for the primary endpoint is reported. Those omissions prevent a quantitative assessment of the study’s main question.

The single-group design means there is no randomized comparator in the record. Even if outcome counts were available, they would describe the study group and would not establish what would have occurred under a different treatment. A causal treatment effect cannot be inferred from a treated-group count alone. This distinction is especially important when reading results without a concurrent comparison.

The safety data show that serious adverse events and other adverse events were recorded, and the record lists deaths and selected serious-event terms. The summary does not provide sufficient detail to establish causation, timing, severity, or the full range of events. In particular, the reported death count is not identified as treatment-related.

Accordingly, the registry record can be used to understand the study’s design, intended endpoint, and selected safety summaries. It cannot support a conclusion about the size or precision of the primary efficacy outcome, a comparative treatment effect, or the cause of recorded deaths and adverse events. Those questions require results and methodological details not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of why design and results must be read together. The registry record identifies a single-group phase II study and a participant-count endpoint at six months. That design can describe outcomes in the enrolled group, but it does not create a randomized estimate comparing regorafenib with another option. A reader needs to distinguish descriptive evidence from a treatment contrast.

The endpoint also illustrates that a named outcome is not enough to reconstruct an analysis. The title refers to participants alive with and without disease progression, while the description specifies response categories based on RECIST v1.0 and MRI. The record does not report the numerical counts or explain how those response categories map onto the endpoint’s disease-status categories. Clear reporting of both definitions and results is necessary to judge what was counted.

The safety summaries show why denominators and event definitions matter. The record identifies participants at risk and participants affected by serious and other adverse events, then lists selected serious-event terms as percentages. Without event-level counts, timing, severity, and attribution, those summaries should not be treated as a causal comparison or a complete safety account.

Finally, planning calculations are not interchangeable with completed-study evidence. The registry record describes planning illustrations based on an observed effect and assumptions involving two arms, while the actual study design is single-group. Such illustrations can demonstrate how assumptions shape planning, but they do not establish observed power or recover missing efficacy results. The case underscores the value of reporting prespecified methods, analysis populations, missing-data handling, estimates, and uncertainty alongside the study design.

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.

A central limitation is the absence of numerical primary endpoint results in the registry record. Although the outcome and timeframe are named, the observed counts and any measure of uncertainty are not reported. This prevents assessment of the study’s main endpoint and makes it impossible to judge its precision from the posted results.

The single-group design is an additional limitation for causal interpretation. There is no randomized concurrent control group, so the record cannot estimate a randomized difference between regorafenib and another treatment. The design may describe outcomes in the treated group, but it cannot by itself separate treatment effects from other influences on disease status or safety outcomes.

The endpoint description leaves operational details unresolved. It cites RECIST v1.0 response criteria and MRI assessment but does not state how these categories were combined with the alive-with-or-without-progression endpoint. It does not report handling of death before assessment, missing scans, unevaluable results, or other unavailable endpoint data. The analysis population and missing-data method are also not reported in the registry record.

Safety reporting is limited to overall affected-participant counts, a death count, and selected serious adverse-event terms with percentages. The record does not provide event-specific counts, timing, severity grades, duration, attribution, or whether participants experienced multiple terms. The deaths are not characterized as treatment-related, and the reported adverse-event summaries do not establish causality.

The registry record does not report a detailed statistical analysis plan, multiplicity strategy, sample-size justification, or primary endpoint inferential analysis. The planning illustrations described in the record use assumptions for a two-arm setup, which is not the recorded single-group design. Together, these gaps limit reproducibility and the strength of conclusions that can be drawn from the posted information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Regorafenib in Patients With Progressive, Recurrent/Metastatic Adenoid Cystic Carcinoma — NCT02098538.
• Registry record last updated 2025-09-10; status last verified 2024-11.
• Results first posted 2025-09-10.
• 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.

18. Record Summary

The registry record describes a completed phase II, single-group study of regorafenib in patients with progressive, recurrent or metastatic adenoid cystic carcinoma. Enrollment was 38. The primary outcome was a participant count concerning survival and disease progression at six months, with response criteria described using RECIST v1.0 and MRI. Numerical primary endpoint results are not reported in the registry record.

Safety summaries list 14 participants affected by serious adverse events among 38 at risk, 38 affected by other adverse events among 38 at risk, and 28 deaths. Selected serious adverse-event terms are reported with percentages, but details on timing, severity, and attribution are not reported. The single-group design supplies no randomized comparator, and the registry record does not report the efficacy analysis population, missing-data handling, or detailed statistical plan.