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 Immune Checkpoint Therapy With Nivolumab Esophageal Squamous Cell Carcinoma (NCT03278626), a na phase 1, phase 2 study. The primary outcome is Phase 1: Number of Unacceptable Toxicity (UT) Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03278626 |
| Phase | Phase 1, Phase 2 |
| Condition | Esophageal Squamous Cell Carcinoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | NYU Langone Health |
| Results posted | Yes |
2. Clinical Question
Population
Patients with locally advanced esophageal squamous cell carcinoma were eligible for this phase I/II study. The registry lists enrollment of 12. It does not report further details about the characteristics of participants who enrolled, such as disease stage within the locally advanced category or other clinical features.
Intervention
The treatment began with nivolumab alone at 240 mg intravenously every 2 weeks for 2 doses. Nivolumab was then combined with paclitaxel, carboplatin, and concurrent radiation. The described chemotherapy schedule was paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks. Radiation was described as 50.4 Gy in 28 fractions, with a dose reduction to 41.4 Gy permitted under the protocol before discontinuing for unacceptable toxicity.
Comparator
The study used a single-group design, with no separate randomized or concurrent control group reported. The registry describes the chemotherapy schedule as matching the CROSS trial regimen, but that reference does not make CROSS a comparison group in this study. The trial therefore does not provide a like-for-like estimate of outcomes against another treatment within its own enrolled population.
Primary question
The primary endpoint was the number of unacceptable-toxicity events in Phase 1 during 92 days, up to 28 days after Day 64. The registry defines these events as recurrent grade 3 or 4 hematologic toxicity despite a prior chemotherapy dose reduction, or toxicity resulting in a delay in chemoradiation of more than 2 weeks. The record does not report the observed number of such events. Consequently, the primary question is identifiable from the protocol description, but its posted result cannot be evaluated from the registry record.
3. Trial Design
This was an open-label, multi-institution phase I/II study of nivolumab with paclitaxel, carboplatin, and radiation for locally advanced esophageal squamous cell carcinoma. The registry identifies a single-group model, no masking, and no randomized allocation. Enrollment is listed as 12. The study status is terminated; the reason for termination is not reported in the registry record.
The treatment description starts with nivolumab alone at 240 mg IVPB every 2 weeks for 2 doses. Nivolumab at 240 mg every 2 weeks was then to be added to paclitaxel and carboplatin. The stated chemotherapy schedule was paclitaxel 50 mg/m2 weekly for 6 weeks and carboplatin AUC 2 weekly for 6 weeks. Concurrent radiation was described as 1.8 Gy per fraction for 28 fractions, to a total dose of 50.4 Gy. The protocol permitted a reduction to 41.4 Gy before discontinuing therapy because of unacceptable toxicity.
The record identifies the study as Phase 1 and Phase 2, but does not report how the phases were operationally separated, whether phase-specific enrollment targets were used, or how decisions to proceed between phases were made. A planned start date of 2017-06-27 and a primary completion date of 2019-11-07 are listed. These dates and the terminated status describe the administrative record, not the reason treatment ended or the outcome of the study.
Because there was no concurrent control group, outcomes can describe the enrolled group receiving the combination, but cannot by themselves establish a comparative treatment effect. Allocation is listed as not applicable, consistent with the single-group design. The registry record does not report a protocol-specific statistical analysis plan, a sample-size justification, or details of any interim decision process.
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 | Nivolimumab+Carboplatin/Paclitaxel+Radiation |
|---|---|
| STARTED | 12 |
| COMPLETED | 7 |
| NOT COMPLETED | 5 |
Reasons for not completing this period:
| Reason | Nivolimumab+Carboplatin/Paclitaxel+Radiation |
|---|---|
| Death | 2 |
| Toxicity | 1 |
| Disease Progression | 2 |
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.
Population: 6 subjects enrolled in Phase 1, and 6 subjects enrolled in Phase 2
| Characteristic | Unit | Nivolimumab+Carboplatin/Paclitaxel+Radiation |
|---|---|---|
| Participants analysed | 12 | |
| Age, Continuous | years | 63.95 (47.03 to 86.17) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 7 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 12 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 3 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 |
| Race (NIH/OMB): White | Participants | 7 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Phase 1: Number of Unacceptable Toxicity (UT) Events, measured over 92 days (up to 28 days after Day 64).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Unacceptable Toxicity Events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the Phase 1 number of unacceptable-toxicity events, assessed over 92 days, up to 28 days after Day 64. The registry definition includes recurrent grade 3 or 4 hematologic toxicity despite a prior chemotherapy dose reduction, and any toxicity causing a chemoradiation delay of more than 2 weeks. This is a count endpoint: it concerns the number of events meeting the definition, rather than a time-to-event measure or a comparative treatment effect.
In general, early-phase studies often track toxicity to characterize whether a regimen can be administered as planned and to identify clinically important tolerability concerns. This endpoint is relevant to a regimen combining immunotherapy, chemotherapy, and radiation because the protocol explicitly defines toxicity-related events that could affect treatment delivery. That general rationale does not establish what the study found. The registry record does not report the observed unacceptable-toxicity count, the number of participants contributing to that endpoint, or an uncertainty interval around the count.
The event definition also matters when interpreting the endpoint. A toxicity must meet one of the stated criteria to count as an unacceptable-toxicity event; not every adverse event necessarily meets that definition. The posted serious adverse-event counts are separate safety information and cannot be substituted for the primary endpoint result. Without the endpoint count and its analysis details, the primary measure cannot be used to quantify the observed frequency or precision of unacceptable toxicity in this study.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a primary safety endpoint but does not post its observed value. It therefore does not establish how many unacceptable-toxicity events occurred under the endpoint definition. There is also no posted estimate, confidence interval, or statistical test for this primary endpoint. The study's primary question can be described, but its numerical answer is not reported in the registry record.
The safety record lists 12 participants at risk for serious adverse events and 6 affected. It also lists 12 at risk for other adverse events and 12 affected. These are descriptive counts, not comparisons with another regimen. The record additionally lists deaths as 2. The serious adverse-event terms each reported at 8.3% are abdominal pain, lung infection, colitis, death, fever, and confusion. The registry does not provide further details about timing, severity grading for each term, relationship to treatment, or whether a participant could contribute to more than one term.
These safety counts should not be read as the primary unacceptable-toxicity result. The endpoint uses specific criteria involving recurrent grade 3 or 4 hematologic toxicity after dose reduction or a treatment delay of more than 2 weeks. The adverse-event listings have different labels and do not show whether those criteria were met. Nor do the event listings establish that an event was caused by the treatment.
The study is single group and open label. Without a concurrent control group, observed counts cannot separate effects associated with the regimen from background risks, the underlying illness, or other factors. This design also does not provide a direct estimate of how outcomes would differ under another treatment. A comparison with a separate study would require careful attention to differences in participants, follow-up, event definitions, and data collection; none of those comparative analyses is reported in the registry record.
No statistical analysis entries are posted. Accordingly, the record does not report inferential results for the endpoint or the safety counts, including p-values or confidence intervals. The posted data support a limited descriptive reading of the listed safety figures, while leaving the primary endpoint result and its precision unknown. The terminated status is recorded, but the reason for termination and its implications for outcome collection are not reported.
9. Statistical Methods Explained
The registry describes a single-group, open-label phase I/II study. That design determines what the results can address: outcomes can be described among participants receiving the study regimen, but there is no randomized control group for estimating a direct treatment contrast. Allocation is listed as not applicable, and masking is listed as none. These design features do not by themselves invalidate descriptive safety reporting; they do limit causal and comparative conclusions.
What does a count endpoint represent?
The primary endpoint is a count of unacceptable-toxicity events, not a proportion, rate, or time-to-event endpoint as described in the record. Its interpretation depends on the event definition and the observation window. Here, the definition concerns recurrent grade 3 or 4 hematologic toxicity despite a prior chemotherapy dose reduction, or toxicity causing a chemoradiation delay of more than 2 weeks. The window is 92 days, up to 28 days after Day 64. In general, counts can be useful for describing how often defined events occurred, but counts alone do not communicate precision or account for unequal observation time. The registry does not report an analysis addressing those issues.
How should uncertainty be understood?
In general, a confidence interval describes the range of values reasonably compatible with observed data under a specified statistical model and procedure. It helps distinguish a point estimate from the uncertainty around that estimate. No confidence interval for the primary endpoint or the listed adverse-event counts is reported in the registry record. Thus, the counts should not be treated as precise estimates of event frequency beyond the enrolled group and the available reporting.
In general, p-values quantify how compatible data are with a specified null hypothesis under assumptions of a statistical test; they do not measure the size or clinical importance of an effect. No p-value or hypothesis test is reported for the primary endpoint. Because the study has no concurrent comparison arm, a conventional between-group test of treatment effect is not available from this design as described.
What do the planning assumptions mean?
The record describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. Such illustrations are hypothetical planning calculations, not observed trial results and not evidence that the study had a particular probability of detecting an effect. They are not the trial's own design rationale. The registry does not report a sample-size justification or any numerical planning estimates in the record.
Those assumptions also do not match the study's reported single-group design: equal allocation between two arms is an assumption for an illustrative comparison, not a description of how participants were assigned in this trial. A calculation based on an observed effect would require that effect estimate and its underlying data, neither of which is reported for the primary endpoint. Any illustration should therefore be read as a hypothetical planning aid, not as observed power, a protocol requirement, or a result of this study.
Why does the adverse-event record need separate interpretation?
In general, adverse events are often summarized by whether participants experienced at least one event and by event terms, while a primary endpoint may use a narrower prespecified definition. Those summaries answer different questions. The record lists counts at risk and affected for serious and other adverse events, along with selected serious-event terms, but does not report a model or an inferential analysis for them. It also does not report how repeated events, overlap between terms, or follow-up duration were handled. The listed counts should therefore be read descriptively rather than as adjusted estimates or evidence of a causal treatment relationship.
Finally, the record does not describe a statistical analysis plan, data handling rules, or analysis populations. It does not report how missing endpoint observations were handled, whether all enrolled participants were included in each analysis, or whether any sensitivity analyses were conducted. These omissions prevent evaluation of model assumptions, analysis choices, and robustness. They are especially important for a count endpoint when the event definition, assessment window, and completeness of follow-up shape the meaning of the estimate.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity plan. Multiplicity arises when a study evaluates several endpoints, subgroups, time points, or statistical hypotheses; repeated testing can affect the interpretation of nominal statistical evidence. The record lists 2 outcome measures, but does not describe a hierarchy beyond identifying the Phase 1 unacceptable-toxicity count as the primary endpoint. It reports no statistical analysis entries or testing procedure. No multiplicity adjustment or strategy for distinguishing confirmatory from exploratory analyses is reported.
Missing-data methods are also not reported. The record does not say how incomplete endpoint assessments, missed visits, early treatment discontinuation, or incomplete adverse-event follow-up were handled. Termination is listed as the study status, but the reason and any consequences for follow-up or data completeness are not reported. It would be inappropriate to assume that every enrolled participant had complete data or that a particular imputation or censoring method was used.
The analysis populations are not reported in the registry record. In particular, it does not identify whether the primary endpoint was evaluated in all enrolled participants, those who began treatment, or a different defined group. The number contributing data to the endpoint and the handling of participants without an assessable endpoint are not stated. These details matter because an event count and its interpretation depend on who was observed and for what period.
In general, multiplicity plans, missing-data procedures, and analysis-population definitions help readers understand how estimates were formed and what uncertainty they carry. Without those details, the posted safety counts remain descriptive, and the unreported primary endpoint cannot be reconstructed or interpreted as a complete analysis.
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 |
|---|---|---|---|
| Nivolimumab+Carboplatin/Paclitaxel+Radiation | 6 | 12 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Nivolimumab+Carboplatin/Paclitaxel+Radiation | 2 of 12 |
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 |
|---|---|
| Nivolimumab+Carboplatin/Paclitaxel+Radiation | 12 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | Nivolimumab+Carboplatin/Paclitaxel+Radiation |
|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | 1 of 12 |
| Lung Infection | Infections and infestations | 1 of 12 |
| Colitis | Gastrointestinal disorders | 1 of 12 |
| Death | General disorders | 1 of 12 |
| Fever | General disorders | 1 of 12 |
| Confusion | Psychiatric disorders | 1 of 12 |
| Aspiration | Respiratory, thoracic and mediastinal disorders | 1 of 12 |
| Myocardial Infarction | Cardiac disorders | 1 of 12 |
| Rash-Morbiliform | Skin and subcutaneous tissue disorders | 1 of 12 |
| Dysphagia | Gastrointestinal disorders | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Nivolimumab+Carboplatin/Paclitaxel+Radiation |
|---|---|---|
| Anemia | Blood and lymphatic system disorders | 11 of 12 |
| Decreased Lymphocyte Count | Investigations | 10 of 12 |
| Decreased Platelet Count | Investigations | 9 of 12 |
| Decreased Wbc Count | Investigations | 9 of 12 |
| Dysphagia | Gastrointestinal disorders | 8 of 12 |
| Decreased Neutrophil Count | Investigations | 7 of 12 |
| Hypokalemia | Metabolism and nutrition disorders | 7 of 12 |
| Nausea | Gastrointestinal disorders | 7 of 12 |
| Constipation | Gastrointestinal disorders | 6 of 12 |
| Fatigue | General disorders | 6 of 12 |
Serious events with the highest arm-level rate: abdominal pain (8.3%), lung infection (8.3%), colitis (8.3%), death (8.3%), fever (8.3%).
The registry lists 12 participants at risk for serious adverse events, with 6 affected. For other adverse events, it lists 12 at risk and 12 affected. These are separate summaries; the record does not explain overlap between the groups or whether any participant experienced multiple events. The counts should not be added together to infer a number of affected participants.
The serious adverse-event terms listed at 8.3% each are abdominal pain, lung infection, colitis, death, fever, and confusion. The record also lists 2 deaths. It does not provide additional detail on timing, cause, severity grade for each term, or attribution to treatment. The term-level percentages do not show whether events occurred in the same or different participants.
These listings are safety descriptions, not estimates of comparative risk. With no control group, there is no within-trial basis for determining whether the listed events were more or less frequent than under another treatment. They also do not directly answer the primary endpoint, which has its own specific definition of unacceptable toxicity. In general, adverse-event summaries require attention to event definitions, observation time, overlap, and attribution. Those details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record describes a phase I/II study of nivolumab combined with paclitaxel, carboplatin, and radiation in patients with locally advanced esophageal squamous cell carcinoma. Its primary endpoint was a defined count of unacceptable-toxicity events over 92 days, up to 28 days after Day 64. The registry also reports serious and other adverse-event counts and selected serious-event terms. These details make the planned treatment and safety questions identifiable.
The record does not report the observed primary endpoint count or any inferential analysis. It therefore does not show how often the specified unacceptable-toxicity events occurred, nor how precisely that frequency was estimated. The safety counts describe what is listed, but lack information on timing, attribution, event overlap, and comparative context. No conclusions about relative safety can be drawn from a single-group record without a concurrent control group.
The study's design also does not establish comparative efficacy. No efficacy result or treatment-effect estimate is reported in the registry record, and a single-group study cannot by itself show how outcomes compare with another regimen. The fact that the chemotherapy schedule was described with reference to the CROSS regimen does not mean that patients receiving that regimen formed a control group in this study.
The terminated status is an administrative fact; the reason for termination is not reported. It should not be interpreted as evidence for a particular safety or efficacy outcome. In general, a trial's results depend not only on its design but also on the completeness of outcome collection, the analysis population, and the statistical methods used. Those details are not reported for the primary endpoint.
The most defensible reading is therefore limited: the registry documents a treatment protocol, enrollment of 12, selected safety summaries, and a primary toxicity endpoint, but does not provide the primary endpoint result or statistical analyses. The record does not establish that the regimen is effective or ineffective, or that the listed safety events were caused by treatment.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the distinction between a clearly specified endpoint and a reported endpoint result. The registry defines unacceptable toxicity with explicit event criteria and a stated assessment window. However, without the observed count, analysis population, or uncertainty estimate, the endpoint's numerical result cannot be evaluated. A well-described measure does not by itself supply evidence about the observed frequency of that measure.
The single-group design is also central to interpretation. It can support description of outcomes among participants receiving the regimen, but it cannot directly estimate a treatment contrast against a concurrent control group. The record's reference to a familiar chemotherapy schedule does not change that design. This is important when readers encounter safety percentages or consider how the regimen compares with treatment elsewhere.
Another statistical issue is the separation between the primary endpoint and broader adverse-event listings. The primary endpoint uses particular toxicity and treatment-delay criteria; the safety listings use event categories. Without a posted analysis linking them, the serious adverse-event counts cannot stand in for the unacceptable-toxicity count.
Finally, the record illustrates why statistical methods and reporting details matter alongside protocol descriptions. No analysis entries, missing-data procedures, analysis populations, or multiplicity plan are reported. The status is terminated, but the reason is not. These gaps leave uncertainty not only about the magnitude of outcomes, but also about completeness and analytical handling. The information available supports careful description of the design and listed safety data, while setting firm limits on statistical conclusions.
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 outcomes is that the registry does not report the observed count for the primary unacceptable-toxicity endpoint. It also does not report an estimate of uncertainty, the number contributing endpoint data, or an analysis method. A reader cannot quantify the endpoint result or assess its precision from the record.
The study is single group and open label, with no concurrent comparator reported. This limits the conclusions to descriptive observations and prevents a direct within-study comparison of outcomes under alternative treatments. The registry lists enrollment of 12, but does not report participant characteristics in enough detail to assess how broadly the enrolled group represents the population named in the study description.
The safety summaries lack several details needed for interpretation: the record does not report timing, attribution, event overlap, or the handling of repeated events. The listed adverse-event counts and terms are not the same as the primary endpoint definition. They should not be used to infer the endpoint count or to identify treatment causation.
The study is marked terminated, but the reason for termination is not reported. The record also does not state whether termination affected follow-up, endpoint assessment, or completeness of reporting. Statistical analysis details, missing-data methods, analysis populations, and multiplicity procedures are not reported. These omissions restrict assessment of potential bias and robustness. The protocol description and posted safety counts are therefore useful for understanding the study's scope, but they do not replace a complete outcome analysis.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Immune Checkpoint Therapy With Nivolumab Esophageal Squamous Cell Carcinoma — NCT03278626.
- Registry record last updated 2022-03-28; status last verified 2022-03.
- Results first posted 2022-03-28.
- 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 an open-label, multi-institution phase I/II, single-group study of nivolumab with paclitaxel, carboplatin, and radiation for locally advanced esophageal squamous cell carcinoma. Enrollment is listed as 12. The study is marked terminated; its reason for termination is not reported.
The Phase 1 primary endpoint is the number of unacceptable-toxicity events during 92 days, up to 28 days after Day 64. The registry defines these events by recurrent grade 3 or 4 hematologic toxicity despite a prior dose reduction, or toxicity causing a chemoradiation delay of more than 2 weeks. The observed endpoint result is not reported in the registry record.
Safety listings report serious adverse events in 6 of 12 at risk and other adverse events in 12 of 12 at risk. Deaths are listed as 2; selected serious-event terms are each reported at 8.3%. The registry contains no statistical analysis entries and does not report analysis populations, missing-data methods, or inferential results. The record supports description of the design and listed safety data, but not a comparative treatment-effect conclusion.