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 Pilot Study of Nivolumab in Pediatric Patients With Hypermutant Cancers (NCT02992964), a na phase 1, phase 2 study. The primary outcome is To Evaluate the Objective Response Rate to Nivolumab in bMMRD Positive Pediatric Patients With Refractory and Recurrent Hypermutated Malignancies.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02992964 |
| Phase | Phase 1, Phase 2 |
| Condition | Refractory or Recurrent Hypermutated Malignancies, Biallelic Mismatch Repair Deficiency (bMMRD) Positive Patients |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 11 |
| Arms in the primary outcome | n/a |
| Lead sponsor | The Hospital for Sick Children |
| Results posted | Yes |
2. Clinical Question
Population
Pediatric patients with recurrent or refractory hypermutated malignancies were eligible, with the brief summary describing ages from 12 months to 18 years. The primary objective specifically concerns bMMRD-positive patients. The endpoint population is described as treated patients with measurable disease.
Intervention
The intervention was nivolumab. The regimen description states that treatment was to be given every 14 days until disease progression or discontinuation because of unacceptable toxicities; treatment could extend up to 2 years for patients showing clinical and radiological benefit. These are registry protocol descriptions, not confirmation of treatment received.
Comparator
There was no comparator arm. The registry describes an open-label, single-arm study, with allocation listed as NA. The design therefore does not provide a concurrent control group for estimating a between-group treatment effect.
Primary question
The primary objective was to evaluate objective response to nivolumab in bMMRD-positive pediatric patients with refractory or recurrent hypermutated malignancies. The endpoint is described as a count of participants, assessed over 5 years (60 months) from enrollment. The number of participants who responded, and an objective response rate estimate, are not reported in the registry record.
This is a question about whether objective responses were observed in a narrowly characterized pediatric population receiving nivolumab, rather than a randomized comparison of nivolumab with another treatment or with no treatment. The registry describes physical assessments, laboratory values, disease assessments, and adverse events related to treatment as relevant assessments for the response objective. It does not report the criteria used to classify a participant as a responder, the schedule of individual assessments beyond the endpoint timeframe, or the response results. Consequently, the record identifies the clinical question and intended endpoint but does not provide the results needed to estimate response or its precision.
3. Trial Design
The registry describes a phase 1/phase 2, open-label, single-arm, multicenter pilot study of nivolumab. Its stated population was pediatric patients with recurrent or refractory hypermutant malignancies, including patients with biallelic mismatch repair deficiency. The brief summary gives an age range from 12 months to 18 years and says the study expected bMMRD syndrome to account for the majority of enrolled patients. That expectation is not a report of the composition of the enrolled group.
The registry lists enrollment as 11 and identifies The Hospital for Sick Children as the sponsor. The recorded start date is 2017-05-15, the primary completion date is 2023-11-20, and the current status is terminated. The reason for termination is not reported in the registry record. The completion date and status alone do not establish why the study ended or whether the planned assessments were completed.
With a single treatment group and allocation listed as NA, the design does not include random assignment or a concurrent control group. Open-label means the registry does not describe masking; masking is listed as none. Such a pilot design can describe treatment exposure, observed responses, and adverse events in the enrolled population. It cannot, by itself, separate treatment effects from the natural course of disease, other care, or differences in who enters the study. These are general limitations of uncontrolled clinical designs.
The regimen description says nivolumab was to be administered every 14 days until disease progression or treatment discontinuation for unacceptable toxicities. It also says treatment could continue up to 2 years in patients with clinical and radiological benefit. These details describe the intended regimen, not adherence, duration actually received, or reasons individual participants stopped treatment. Those participant-level details are not reported in the registry record.
The registry describes a pilot study, but a sample-size justification and the rationale for the planned enrollment are not reported in the registry record. Nor does the record establish that the posted enrollment represents the number who received treatment or were eligible for the primary endpoint.
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 | Nivolumab |
|---|---|
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Treated patients with measurable disease
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 | Nivolumab |
|---|---|---|
| Participants analysed | 10 | |
| Age, Categorical: <=18 years | Participants | 10 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 5 |
| Race and Ethnicity Not Collected | Participants | — |
6. Primary Endpoint
The registry lists the primary outcome as To Evaluate the Objective Response Rate to Nivolumab in bMMRD Positive Pediatric Patients With Refractory and Recurrent Hypermutated Malignancies, measured over 5 years (60 months) from date of enrollment.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is described as objective response, with the measure expressed as a count of participants. The endpoint population is treated patients with measurable disease, while the primary objective names bMMRD-positive pediatric patients with refractory or recurrent hypermutated malignancies. The stated timeframe is 5 years (60 months) from the date of enrollment. The record says response assessment would draw on physical assessments, laboratory values, disease assessments, and adverse events related to treatment.
Objective response is used in oncology studies to describe a defined category of tumor response based on clinical assessment. In general, a response endpoint can offer a direct way to describe whether disease assessments indicate a reduction or other qualifying change. Its interpretation depends on the assessment criteria, evaluation schedule, and rules for handling missing or unevaluable assessments. The specific response criteria and those rules are not reported in the registry record.
The registry gives no responder count, response proportion, or confidence interval. A count alone would indicate how many participants met a response definition; a rate would additionally require an appropriate denominator. Neither an observed count nor a rate can be inferred from the enrollment figure, because the endpoint population is restricted to treated patients with measurable disease and the number meeting that description is not reported in the registry record. The stated objective therefore should not be mistaken for a posted efficacy result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive point is that the registry defines a study objective but does not post its efficacy result. It lists objective response as the primary endpoint and describes a target population, assessment components, and a timeframe. It does not report the number of participants who responded, the response rate, or an uncertainty interval. Accordingly, the posted record does not permit an estimate of the magnitude or precision of response in the endpoint population.
The enrollment is listed as 11, but this figure should not automatically be used as the denominator for the response endpoint. The primary population is treated patients with measurable disease, and the registry does not report how many enrolled participants were treated, had measurable disease, or were assessable for response. The enrollment figure alone cannot resolve these distinctions.
The design is single-group and open-label, with no concurrent comparator. Any observed response count, if reported elsewhere, would describe outcomes among participants in this study; it would not estimate a randomized contrast. In general, an uncontrolled study cannot distinguish the contribution of treatment from other explanations for observed outcomes. That limitation is especially important when using a pilot study to discuss comparative benefit. The registry record does not offer a control-group outcome or an adjusted treatment-effect estimate.
Safety counts are listed for the nivolumab group: 2 serious adverse events among 10 at risk, 7 other adverse events among 10 at risk, and 6 deaths. The two serious terms listed as most frequent are pancreatitis and hydrocephalus, each with 10.0%. These figures describe what the registry reports, but the record does not provide event-level timing, participant-level overlap, attribution details, or a comparative safety rate. The term “serious” should not be treated as synonymous with “caused by treatment.”
The record gives the status as terminated, but the reason is not reported in the registry record. The status cannot establish whether termination was related to safety, efficacy, recruitment, feasibility, or another cause. Likewise, no interim analysis, monitoring plan, or statistical analysis plan is reported in the registry record. These absences limit interpretation of how outcome information was collected and analyzed.
Overall, the registry record supports a description of the intended study question, design, and selected safety counts. It does not support an efficacy estimate, a comparison against another treatment, or a causal explanation for the reported deaths or adverse events. Readers should distinguish the study’s intended endpoint from a numerical result and distinguish a registry-reported count from a complete analysis of all participants and outcomes.
9. Statistical Methods Explained
Statistical interpretation begins by separating the study question, the endpoint definition, and the analysis actually reported. The registry identifies an objective-response objective, but it does not list an outcome analysis. The distinction matters: a planned measure tells readers what investigators intended to assess, whereas an analysis reports what was observed and how uncertainty was quantified. In this record, the intended primary measure is described, but an efficacy estimate is not reported.
What does a single-group design estimate?
In general, a single-group study can describe outcomes in the participants who received the intervention and were assessed. It has no concurrent randomized group to provide a direct contrast. A response count or rate from such a study would therefore be a descriptive result for its observed population, not a randomized estimate of the difference between treatment strategies. Differences in patient characteristics, disease course, other care, and assessment can affect outcomes; without a suitable comparison, their influence cannot be separated from treatment effects using the study design alone.
The registry lists allocation as NA, masking as none, and the model as single group. This is consistent with the description of an open-label, single-arm pilot study. It would be inappropriate to interpret the design as randomized or blinded, or to imply that a control group exists. The registry does not report an adjusted comparative analysis.
How should an objective-response count be read?
In general, an objective-response count is the number of participants meeting a prespecified response definition. A rate expresses that count relative to a defined analysis population. The denominator must match the stated population and rules for response assessment. Here the endpoint population is described as treated patients with measurable disease; the record does not report its size or a responder count. The listed enrollment cannot substitute for those endpoint-specific quantities.
A confidence interval, when reported, conveys the statistical uncertainty around an estimate under the analysis assumptions. It does not represent a range containing all individual outcomes, and it does not correct for biases in study design or measurement. No confidence interval for objective response is reported in the registry record. Without an estimate and its uncertainty, the precision of the primary endpoint cannot be assessed from this record.
What does the timeframe tell the reader?
The primary endpoint timeframe is 5 years (60 months) from enrollment. This identifies the stated observation window for the objective, but it does not show that every participant was observed for the full timeframe or specify the timing and frequency of all assessments. The record refers to a protocol study calendar for additional assessment details, but those details are not reported in the registry record. Follow-up completeness and the handling of participants with incomplete observation are also not reported.
What can the safety counts establish?
In general, an adverse-event count describes recorded events or affected participants according to a particular registry reporting convention. Interpretation depends on whether a count refers to events or people, the period of observation, severity definitions, and whether investigators judged an event related to treatment. The registry reports 2 serious adverse events among 10 at risk, 7 other adverse events among 10 at risk, and 6 deaths. It also lists pancreatitis and hydrocephalus at 10.0% each among the top serious terms. The record does not provide enough detail to determine timing, overlap among terms, treatment attribution, or whether these figures represent a complete safety analysis.
General statistical caution applies to comparisons of event frequencies: exposure time, follow-up, definitions, and the population at risk should be comparable. A single-group safety listing cannot establish an excess risk relative to an unexposed or alternative-treatment group. No such comparison is reported in the registry record.
What do the planning assumptions mean?
The sample-size assumptions describe planning illustrations based on an observed effect, not the trial’s own design. The listed assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. The illustrations are not reported as an observed-power analysis, and their assumptions do not turn this single-group trial into a two-arm study. The registry does not report the trial’s own sample-size justification or a comparative effect estimate to interpret as an efficacy result.
In general, a sample-size calculation asks what number of participants or events would be needed under specified assumptions to detect a chosen effect with a chosen error rate and power. It is a design aid, not evidence that an effect exists. Planning for a fraction of an observed effect explores sensitivity to a smaller target effect, but it depends on the effect estimate and other assumptions used. The registry record does not report numerical planning results for this trial. Such illustrations should therefore be read separately from observed outcomes and not as evidence about the trial’s achieved ability to detect an effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a statistical analysis plan, a multiplicity adjustment, or an interim-analysis plan. It lists one primary outcome measure and no analyses. This does not establish whether additional analyses were conducted outside the registry; those details are not reported in the registry record.
In general, multiplicity arises when investigators test or estimate several outcomes, subgroups, time points, or treatment contrasts. Repeated statistical testing can increase the chance of a seemingly notable result arising by chance. Prespecified priorities and appropriate methods help readers understand how multiple questions were handled. Because the record does not describe a testing strategy, it is not possible to determine how multiplicity was addressed, if relevant.
Missing-data handling is also not reported in the registry record. The record does not describe how participants without measurable disease, participants who discontinued treatment, or participants lacking later assessments would be handled in the primary endpoint analysis. General methods may treat missing or unevaluable outcomes differently, and those choices can affect the interpretation of a response estimate. No assumption about those rules should be inferred.
The endpoint population is defined as treated patients with measurable disease, but the registry does not report the number meeting that definition or the analysis population used. The listed enrollment of 11 is not enough to determine endpoint eligibility, treatment exposure, or completeness of assessment. The analysis population and participant flow are not reported in the registry record.
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 |
|---|---|---|---|
| Nivolumab | 2 | 10 | 20.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Nivolumab | 6 of 10 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Nivolumab | 7 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Nivolumab |
|---|---|---|
| pancreatitis | Gastrointestinal disorders | 1 of 10 |
| hydrocephalus | Nervous system disorders | 1 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Nivolumab |
|---|---|---|
| Headache | Nervous system disorders | 3 of 10 |
| Fatigue | General disorders | 3 of 10 |
| Other gastrointestinal | Gastrointestinal disorders | 3 of 10 |
| Other (dyspnea, flu-like symptoms, cystitis, arthralgia) | General disorders | 3 of 10 |
| Other neurologic | Nervous system disorders | 2 of 10 |
| Other skin/rash | Skin and subcutaneous tissue disorders | 2 of 10 |
| Papilledema | Eye disorders | 1 of 10 |
| Lipase increased | Investigations | 1 of 10 |
| Lymphopenai | Investigations | 1 of 10 |
| Other laboratory | Investigations | 1 of 10 |
Serious events with the highest arm-level rate: pancreatitis (10.0%), hydrocephalus (10.0%).
The registry lists safety information for the nivolumab group, with 10 at risk. It reports 2 serious adverse events, 7 other adverse events, and 6 deaths. The top serious terms are pancreatitis and hydrocephalus, each listed as 10.0%. These are registry counts and percentages; they should be read as reported rather than as a complete account of event timing or clinical course.
The record does not clarify whether the event counts refer to people or event episodes, whether a person could appear under more than one term, or how long participants were observed for safety. It also does not report a detailed attribution assessment showing whether investigators considered each event related to nivolumab. A serious adverse event is a classification of seriousness and does not, by itself, mean that treatment caused the event.
The death count should not be equated with treatment-related deaths: attribution and timing are not reported in the registry record. Nor can these safety figures establish comparative risk, because the study has no control arm. In general, interpreting safety requires context about exposure, follow-up, event definitions, and the population under observation. Those details are not reported in the registry record, so the figures are descriptive rather than a causal or comparative safety estimate.
12. What the Result Does, and Does Not, Mean
The record documents a pilot study designed to assess objective response to nivolumab in pediatric patients with recurrent or refractory hypermutated malignancies, with a primary objective focused on bMMRD-positive patients. It describes an open-label, single-group design and an intended response assessment timeframe. These details clarify what the study set out to ask, but they do not answer whether objective responses occurred or how frequent they were.
The primary response result is not reported in the registry record. There is no posted responder count, response rate, or confidence interval to establish the observed magnitude or statistical precision of the endpoint. The listed enrollment cannot replace those outcome data because the endpoint applies to treated participants with measurable disease, and the endpoint-specific analysis population is not reported.
The record also lists adverse-event counts and deaths. These counts are relevant descriptive safety information, but the available details do not establish whether events were caused by treatment or how risks compare with another intervention. The single-arm design has no concurrent control group. General causal interpretation is therefore limited even if outcome counts are available.
The terminated status is a registry status, not an explanation for why the study ended. The reason for termination is not reported in the registry record. It should not be interpreted as proof of a safety problem, lack of efficacy, or any other particular outcome. Likewise, the brief-summary expectation that bMMRD syndrome would account for most enrollment is not an observed description of the enrolled participants.
The appropriate statistical reading is narrow: the record describes a study question, a planned endpoint, design features, and selected safety listings. It does not supply the efficacy analysis needed to estimate response, nor the detail needed to make a causal safety assessment. No clinical recommendation follows from these registry entries alone.
13. Why This Trial Matters Statistically
This trial is statistically notable because it addresses a rare and specifically described pediatric population through a pilot design. The primary objective concerns bMMRD-positive patients with refractory or recurrent hypermutated malignancies, while the wider study description includes pediatric patients with recurrent or refractory hypermutant cancers. In such a setting, a small single-group study can provide descriptive information about treatment exposure and observed outcomes. Its statistical interpretation must remain aligned with that limited design.
The key lesson is the difference between a clear clinical question and a reported numerical answer. The registry specifies objective response as the primary endpoint but does not report its result. Without the response count, endpoint denominator, and uncertainty estimate, readers cannot determine the size or precision of an observed response proportion. A study title, endpoint definition, and enrollment figure do not substitute for outcome analysis.
The design also illustrates why a favorable or unfavorable outcome count in a single arm is not equivalent to a comparative treatment effect. General statistical reasoning requires a comparator to estimate a difference between strategies with protection against important sources of bias. This record has no control arm, so any reported outcome would need to be interpreted as descriptive of the assessed group.
Finally, the safety listing illustrates the difference between recording an adverse event and attributing it to treatment. Counts, terms, and deaths require context about observation, exposure, and attribution. The registry provides selected counts but not those details. Clear distinctions between planned outcomes, observed results, uncertainty, and causal interpretation are especially important when interpreting a pilot study with no reported efficacy analysis.
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 primary limitation for interpreting efficacy is that the registry record does not report the objective-response result. It gives no responder count, response rate, or confidence interval. The endpoint population is treated patients with measurable disease, but the size and composition of that population are not reported. The enrollment figure therefore does not identify the denominator for the primary endpoint.
The single-group, open-label design has no concurrent comparator and no masking. These design features limit comparative and causal interpretation. The record also does not report the criteria used to classify objective response, details of the assessment schedule, or rules for handling unevaluable outcomes. Those matters affect how a response result would be interpreted.
Participant flow, treatment exposure, duration actually received, adherence, discontinuation reasons, and completeness of follow-up are not reported in the registry record. The reason for the terminated status is also not reported. It is not possible to infer why the study ended or whether outcome collection was complete.
For safety, the registry lists counts and top serious terms but does not report detailed event timing, overlap, attribution, exposure-adjusted rates, or a control-group comparison. The available listing cannot establish causality or comparative risk. The analysis plan, multiplicity handling, missing-data methods, interim analyses, and sample-size justification are not reported in the registry record. Together, these omissions constrain assessment of both statistical precision and the robustness of any interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pilot Study of Nivolumab in Pediatric Patients With Hypermutant Cancers — NCT02992964.
- Registry record last updated 2026-11-05; status last verified 2026-10.
- Results first posted 2026-11-05.
- 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.
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18. Record Summary
The registry describes NCT02992964, a phase 1/phase 2, open-label, single-arm, multicenter pilot study sponsored by The Hospital for Sick Children. The study concerned nivolumab in pediatric patients with recurrent or refractory hypermutated malignancies, including bMMRD-positive patients. Enrollment is listed as 11; the status is terminated, and the reason for termination is not reported in the registry record.
The primary objective was to evaluate objective response in bMMRD-positive pediatric patients. The endpoint population is described as treated patients with measurable disease, with assessment over 5 years (60 months) from enrollment. The response result is not reported in the registry record. Safety listings report 2 serious adverse events among 10 at risk, 7 other adverse events among 10 at risk, and 6 deaths; pancreatitis and hydrocephalus are each listed at 10.0% among the top serious terms. The single-group design and incomplete outcome reporting limit efficacy and comparative safety interpretation.