This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab in Combination With Mitotane in Patients With Advanced Adrenocortical Carcinoma (NCT05634577), a na phase 2 study. The primary outcome is Overall Response Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT05634577 |
| Phase | Phase 2 |
| Condition | Adrenocortical Carcinoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
People with advanced adrenocortical carcinoma, a cancer of the adrenal cortex. The registry record lists 3 participants enrolled. It does not report participant characteristics or describe how closely the enrolled group represented the broader population of people with this cancer.
Intervention
The regimen combined mitotane with pembrolizumab. Participants first received mitotane alone during a lead-in phase, described as 4 weeks long in most participants, and then began pembrolizumab with mitotane.
Comparator
There was no separate control group. This was a single-group study, with allocation listed as not applicable and masking listed as none. The lead-in phase was part of the treatment sequence, not a parallel comparison group.
Primary question
The primary question was whether the combination produced tumor reduction meeting the registry’s definition of overall response rate, assessed using RECIST1.1 criteria during combination therapy. The registry states that no participant data were collected for this endpoint because the study terminated before participants reached the prespecified assessment time points. Therefore, the primary question has no reported answer in this record.
The study also listed overall survival, progression-free survival, and side effects and the relationship between response and drug level as secondary outcomes. Those outcomes do not create a control comparison: the design remains a single group, and the registry record does not report analyses for these outcomes. The clinical question is therefore a planned evaluation of response and safety, rather than evidence from a completed comparison of the regimen with another treatment or with no treatment.
3. Trial Design
This was a Phase II, single-group study sponsored by M.D. Anderson Cancer Center. The registry record lists an enrollment of 3 and a status of terminated. The recorded start date is 2023-03-23, and the primary completion date is 2024-07-10. It lists no masking and no randomized allocation. Because there was only one group, the design does not support a like-for-like comparison between the combination and a control treatment.
The treatment sequence began with mitotane alone in a lead-in phase. The registry describes that period as 4 weeks long in most participants; participants then began pembrolizumab while receiving mitotane. This sequence helps describe the intervention, but it does not establish that every participant followed an identical schedule. Details about any variation in treatment duration or dose are not reported in the registry record.
The primary outcome was overall response rate, defined through assessment of tumor reduction by RECIST1.1 criteria. Its stated timeframe was during active intervention with combination therapy. The registry lists overall survival and progression-free survival among secondary outcomes, along with side effects and the relationship between response and drug level. It does not report results for those secondary outcomes in the registry record for this record.
The record states that the study terminated before participants reached the prespecified assessment time points, and that data were not collected for any participant for the primary outcome. The reason for termination, the intended follow-up schedule, and the detailed statistical analysis plan are not reported in the registry record. The record also does not report whether the termination was related to efficacy, safety, recruitment, or another circumstance; no such explanation should be inferred from the status alone.
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
| Stage | Combination Pembrolizumab With Mitotane |
|---|---|
| STARTED | 3 |
| COMPLETED | 1 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Combination Pembrolizumab With Mitotane |
|---|---|
| Lost to Follow-up | 1 |
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: Data were not collected for any participant due to study termination prior to participants' assessment at the pre-specified time points.
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.
| Characteristic | Unit | Combination Pembrolizumab With Mitotane |
|---|---|---|
| Participants analysed | 3 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 2 |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response Rate, measured over From time of active itervention (Combination therapy).
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
Overall response rate is intended to describe the proportion of participants whose tumors meet defined criteria for response. In this study, tumor reduction was to be assessed using RECIST1.1 criteria, with the primary outcome assessed during combination therapy. Such a response endpoint can provide a structured way to characterize tumor change rather than relying only on an informal description. The criteria establish how tumor findings are classified, but an endpoint value still requires observations from participants at the relevant assessment times.
No primary endpoint value is reported. The registry explicitly states that data were not collected for any participant because the study terminated before participants reached the prespecified assessment time points. Consequently, the record does not provide a response count, a response proportion, or a precision estimate for overall response rate. This is not a finding of no response: it is an absence of endpoint observations.
The outcome’s stated timeframe refers to active intervention with combination therapy, following the mitotane lead-in. The registry does not report further details about the assessment schedule or the criteria for handling participants who might not complete an assessment. Those protocol details are not reported in the registry record. The planned endpoint is clear at a broad level, but it cannot be used to estimate the frequency of tumor response in this study from the recorded results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the study enrolled 3 participants but reports no collected primary endpoint data. The registry attributes this absence to termination before participants reached the prespecified assessment time points. As a result, there is no reported overall response rate to interpret, and no estimate of how often participants met RECIST1.1 response criteria. An unreported response outcome must not be treated as a response rate of zero.
The design also limits what the study could establish even if outcome data had been recorded. It was a single-group study without random allocation, masking, or a separate comparator. A single-group response estimate could describe outcomes among enrolled participants, but it would not by itself distinguish a treatment effect from other explanations for observed change. Here, the lack of primary endpoint data means that even this descriptive estimate is unavailable.
The registry lists 3 participants at risk for serious adverse events, with 1 affected, and 3 at risk for other adverse events, with 0 affected. It also lists no deaths. These counts describe the recorded safety results for a very small enrolled group; they do not establish the frequency of events in a larger population or permit a reliable comparison with another treatment. Nausea and fever are listed among the top serious adverse event terms, each at 33.3%. These listed terms should be read as registry safety entries, not as a complete clinical account or proof of a causal relationship to treatment.
The record lists 4 outcome measures and 0 analyses. It does not report statistical estimates, confidence intervals, or hypothesis-test results. Without an endpoint estimate and its uncertainty, readers cannot assess the precision of a response result. The absence of analyses should not be interpreted as evidence that the treatment had no effect; it means that the registry record does not present an analyzed primary outcome.
Overall, the posted data document a terminated study with limited enrollment, no collected primary endpoint data, and a small set of safety counts. They do not support a quantitative conclusion about tumor response, survival, or comparative benefit. The study’s status and missing endpoint observations define the limits of interpretation; neither should be converted into an efficacy conclusion.
9. Statistical Methods Explained
Statistical interpretation depends on both the design and the observations actually recorded. In this study, the design planned a response assessment during combination therapy, using RECIST1.1 criteria. The registry then reports that termination occurred before the prespecified assessment time points and that no participant had primary outcome data collected. The planned method therefore cannot yield a response estimate from the recorded observations.
What does an overall response rate measure?
In general, an overall response rate summarizes how many participants meet a prespecified definition of tumor response among those assessed. The definition matters: in this study, the registry identifies RECIST1.1 criteria as the basis for assessing tumor reduction. A response rate is not interchangeable with a survival outcome, a measure of symptom change, or a general judgment about whether a treatment is beneficial. It answers a narrower question about the classification of tumor change under specified assessment criteria.
To estimate a response rate, a study needs participant-level response assessments and a defined denominator. When assessments are not collected, the response status of participants is unknown for that endpoint. It is statistically incorrect to assign all participants a nonresponse solely because the response data are missing. The registry’s statement that no primary outcome data were collected means that neither the numerator nor a usable endpoint denominator is reported.
Why does the single-group design matter?
In general, a single-group study describes outcomes in participants receiving the study regimen, without a concurrent control group. If outcomes are observed, the study may characterize what happened to those enrolled participants. It cannot make the same direct comparison as a randomized trial with a control arm. Differences in participant characteristics, disease course, and other influences cannot be separated from treatment effects by a randomized comparison in this design. In this record, no response data are available even for a descriptive estimate within the single group.
The lead-in phase is part of the treatment sequence: participants first received mitotane alone, described as a 4-week period in most participants, and then began pembrolizumab. It is not a randomized control arm. The registry does not report analyses that separate outcomes during the lead-in from outcomes during combination therapy, and the primary outcome timeframe is specified as the combination-therapy period.
What would a confidence interval contribute?
In general, a confidence interval describes the range of values compatible with an estimate under a statistical method and its assumptions. It communicates uncertainty that a point estimate alone cannot show. A narrow interval generally indicates greater precision than a wide interval, while the interpretation also depends on the analysis design and data quality. No primary response estimate or confidence interval is reported in this registry record. With no endpoint observations, there is no reported response estimate around which to interpret statistical precision.
What can event counts tell readers?
Safety counts report how many participants were at risk for an event and how many were recorded as affected. They are useful for describing observed events in the enrolled group, but counts from a small group are inherently limited as a guide to how often events occur more broadly. They do not alone show whether an event was caused by treatment, how severe it was in clinical terms, or whether an event was more frequent than it would have been under another treatment. The registry lists the serious and other adverse event counts separately, and those categories should not be combined or treated as interchangeable.
General statistical considerations such as over-dispersion are relevant when count data vary more than a simple model expects. However, the registry record does not report a model for adverse events, a formal comparison, or a variance estimate. It would therefore be inappropriate to attribute a particular statistical method to this study or to use a general modeling concept as if it were part of the reported analysis.
How should planning illustrations be understood?
In general, sample-size calculations describe planning under stated assumptions; they are not observed outcomes or a measure of the evidence produced by a completed study. The registry’s design rationale and sample-size justification are not reported in the registry record. No planning illustration can substitute for missing outcome observations, and no sample-size value should be interpreted as observed power. The record does not report a completed primary analysis from which to assess the response effect or its uncertainty.
The record lists 0 analyses. It does not report a statistical model, adjustment method, interim analysis, or analysis population for the primary outcome. These are not details that can be reconstructed from the study title, phase, or endpoint label. The most defensible statistical reading is therefore descriptive: the planned response endpoint is identifiable, but the registry reports no data with which to estimate it.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity refers, in general, to the statistical issue created when several outcomes or comparisons are tested. The record lists overall response rate as the primary outcome and names overall survival, progression-free survival, and side effects and the relationship between response and drug level as secondary outcomes. It does not report a testing hierarchy, a multiplicity adjustment, or a statistical analysis plan describing how multiple outcomes would be interpreted. Those details are not reported in the registry record, so it is not possible to determine whether or how the study planned to control the chance of misleading findings across outcomes.
Missing data are central to interpretation. The registry states that no data were collected for any participant for the primary outcome because the study terminated before participants reached the prespecified assessment time points. This is not a small amount of missingness that can be described by a reported imputation method; no primary endpoint observations are reported. The registry does not report how missing outcome data would have been handled under the planned analysis.
The record lists 0 analyses and does not report an analysis population, such as a definition of which participants would be included in the primary analysis. It also does not report whether any participants withdrew, what follow-up was completed, or how the secondary outcomes were analyzed. These omissions should not be filled by assuming a standard approach. In particular, no statistical adjustment, missing-data procedure, or population definition can be attributed to the trial from the registry entry alone.
Because the primary outcome is unavailable and other analyses are not reported, there are no reported inferential results for which multiplicity adjustments or robustness checks can be evaluated. This limits both the ability to assess the planned analysis and the ability to draw conclusions from the secondary outcomes.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Combination Pembrolizumab With Mitotane | 1 | 3 | 33.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Combination Pembrolizumab With Mitotane | 0 of 3 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Combination Pembrolizumab With Mitotane | 0 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | Combination Pembrolizumab With Mitotane |
|---|---|---|
| Nausea | Gastrointestinal disorders | 1 of 3 |
| Fever | General disorders | 1 of 3 |
Serious events with the highest arm-level rate: nausea (33.3%), fever (33.3%).
The registry reports serious adverse events for the combination group among 3 participants at risk: 1 participant was affected. For other adverse events, 3 participants were at risk and 0 were affected. The record lists 0 deaths. These are counts in the enrolled group, not comparative estimates of risk against another treatment, because the study had no control group.
Nausea and fever are listed among the top serious adverse event terms, each at 33.3%. These term-level entries do not establish whether the events occurred in the same participant or in different participants. The registry figures also do not, by themselves, describe timing, duration, severity beyond the serious-event classification, or whether investigators judged an event to be caused by treatment. The record does not report those details.
With only 3 participants enrolled, the safety counts are a narrow description of recorded events in this study. A count of 0 for other adverse events does not demonstrate that such events cannot occur, and the serious-event count does not establish a rate in a broader population. The figures should be read as limited registry observations, not as a comprehensive safety profile.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a Phase II single-group study of pembrolizumab with mitotane enrolled 3 participants and was terminated. It also documents the planned treatment sequence and the intended primary endpoint: tumor response assessed using RECIST1.1 criteria during combination therapy. For that primary endpoint, however, the record says that no participant data were collected because the study ended before the prespecified assessment time points.
Accordingly, the record does not show whether participants experienced a tumor response under the study’s criteria. It does not report a response estimate, a confidence interval, or an analysis that could quantify the endpoint. The absence of recorded response data is not evidence of no response, just as the study’s planned objective is not evidence that a response occurred. The distinction between an unanswered question and a negative result is essential.
The safety entries describe events recorded among a small group, including 1 participant affected by a serious adverse event and 0 affected by other adverse events, with 0 deaths listed. These counts do not establish comparative safety or the likelihood of events in a broader population. The listed serious-event terms are not enough to determine causation or provide a complete account of the clinical experience.
The single-group design also means there was no concurrent comparator for separating treatment-associated outcomes from other influences. Even if primary response data had been available, a response observed in one group would not provide the same evidence as a randomized comparison. In this record, the lack of primary endpoint data further narrows interpretation.
The result is therefore a record of an intended evaluation that did not produce a reported primary response assessment. It cannot support a conclusion about whether the combination changed tumor outcomes, survival, or the course of disease. Nor does it establish that the regimen had no effect. It documents what was planned, the limited enrollment, termination, and the outcomes that are or are not reported.
13. Why This Trial Matters Statistically
This study illustrates a basic but important statistical distinction: a planned endpoint is not the same as an observed endpoint. The registry clearly identifies overall response rate and the assessment criteria, but it also states that no participant data were collected for that outcome. Without observations, statistical analysis cannot estimate a response rate or quantify uncertainty. This distinction prevents an unanswered study question from being mistaken for a negative finding.
The record also shows why design details matter when reading clinical results. A single-group study has no concurrent control arm, so it cannot directly compare outcomes between the combination and an alternative. In this case, the enrollment was 3, and the study terminated before the primary assessment time points. Both the design and the missing endpoint data constrain what can be learned from the record.
Safety counts require similarly careful reading. Counts among a small enrolled group can document events that were recorded, but they do not establish comparative risks or a general event frequency. A zero count for one category is not proof that the event is impossible, while a recorded serious event does not by itself establish treatment causation. Clear separation of event counts, denominators, and causal interpretation is central to responsible statistical communication.
Finally, the record lists secondary outcomes but no analyses. That makes it important to distinguish the outcomes a study intended to evaluate from the results it actually reports. A trial can have clinically relevant aims and still provide little analyzable evidence when it terminates before measurement. Accurate interpretation respects both the value of the research question and the limits of the available observations.
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 most direct limitation is that the registry reports no primary endpoint data for any participant. The stated reason is termination before the prespecified assessment time points. Without those data, overall response rate cannot be estimated, and there is no reported precision measure for the primary endpoint.
Enrollment was 3, which sharply limits the descriptive scope of the safety observations. The record lists 1 participant affected by a serious adverse event, 0 affected by other adverse events, and 0 deaths. These counts cannot establish how often events would occur in a broader population or support a comparison with another treatment. No comparator group was included.
The single-group, unmasked design means that the study was not structured as a randomized, blinded comparison. The registry does not report enough information to assess whether any other design protections or analysis procedures were planned. The reason for termination is not reported in the registry record, so its context should not be inferred.
Details that would help evaluate the intended analyses are also not reported in the registry record. These include the statistical analysis plan, the planned analysis population, missing-data handling, any interim analyses, and the sample-size justification. The registry lists 0 analyses, and it does not provide primary or secondary outcome estimates for interpretation. The detailed follow-up and assessment schedule is not reported beyond the endpoint timeframe and the statement about prespecified assessment time points.
These limitations mean the record is informative about the study’s design and its incomplete primary outcome evaluation, but it does not provide a quantitative efficacy assessment. The safety entries should likewise be treated as limited observations rather than a comprehensive estimate.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab in Combination With Mitotane in Patients With Advanced Adrenocortical Carcinoma — NCT05634577.
- Registry record last updated 2025-06-19; status last verified 2025-06.
- Results first posted 2025-06-19.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a Phase II, single-group study of pembrolizumab in combination with mitotane for advanced adrenocortical carcinoma. It lists M.D. Anderson Cancer Center as sponsor, 3 participants enrolled, no masking, and a terminated status. Participants were to receive a mitotane lead-in, described as 4 weeks in most participants, before beginning pembrolizumab.
The primary outcome was overall response rate assessed by RECIST1.1 during combination therapy. The registry states that no primary outcome data were collected because the study terminated before participants reached the prespecified assessment time points. It lists 4 outcome measures and 0 analyses. Safety entries include 1 participant affected by a serious adverse event, 0 affected by other adverse events, and 0 deaths.
The record does not report a primary response estimate, comparative results, or a detailed statistical analysis plan. Its main statistical implication is that the planned efficacy endpoint remains unanswered in the posted results.