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 Birinapant and Intensity Modulated Re-Irradiation Therapy in Treating Patients With Locally Recurrent Head and Neck Squamous Cell Carcinoma (NCT03803774), a na phase 1 study. The primary outcome is Incidence of Dose-limiting Toxicities (DLTs) and Grades 1-5 Serious and/or Non-serious Toxicities Related (Except for Unrelated and Unlikely) to Intervention.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03803774 |
| Phase | Phase 1 |
| Condition | Locally Recurrent Head and Neck Squamous Cell Carcinoma, Nasopharyngeal Squamous Cell Carcinoma, Sinonasal Squamous Cell Carcinoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 13 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
Patients with locally recurrent head and neck squamous cell carcinoma are the main population described. The registry record also lists nasopharyngeal and sinonasal squamous cell carcinoma. The brief summary characterizes recurrence as cancer returning at or near the original tumor site. Further eligibility details and a more specific description of the population analyzed are not reported in the registry record.
Intervention
The intervention combines birinapant with intensity-modulated re-irradiation therapy (IMRRT). The treatment description says IMRRT begins on day 1 and is given 5 days a week, Monday through Friday. Birinapant is given intravenously over 30 minutes on days 2 and 9 of each cycle. Treatment repeats every 3 weeks for up to 2 cycles unless disease progression or unacceptable toxicity occurs.
Comparator
There is no separate control group described. The registry identifies the study model as single-group and allocation as not applicable, with no masking. Its treatment-group descriptions list birinapant doses of 5.6 mg/m^2, 11 mg/m^2, 17 mg/m^2, and 24 mg/m^2, each alongside IMRRT. These dose groups should not be treated as randomized, like-for-like comparisons.
Primary question
The primary question concerns the incidence of dose-limiting toxicities and grade 1-5 serious or non-serious toxicities related to the intervention, excluding events judged unrelated or unlikely to be related. The assessment timeframe is up to 42 days post-treatment. This is a Phase I safety and dose-focused question, not a direct test of comparative effectiveness. The registry record does not report a numerical result for this primary endpoint.
3. Trial Design
This is a Phase I, single-group study of birinapant given with intensity-modulated re-irradiation therapy in patients with recurrent head and neck squamous cell carcinoma. The registry lists an enrollment of 13 and identifies the allocation as not applicable, the masking as none, and the model as single-group. Although the treatment descriptions list several birinapant dose levels, the record does not describe a randomized comparison between them. These groups therefore do not function as independent control and treatment arms for estimating a treatment effect.
The treatment regimen combines radiation with intravenous birinapant. IMRRT begins on day 1 and is scheduled 5 days a week, Monday through Friday. Birinapant is administered over 30 minutes on days 2 and 9 of each cycle. Cycles repeat every 3 weeks for up to 2 cycles if disease progression or unacceptable toxicity does not intervene. The group titles list IMRRT 2 Gray(Gy) with birinapant doses of 5.6 mg/m^2, 11 mg/m^2, 17 mg/m^2, and 24 mg/m^2. The registry record does not give further details about how assignment to these dose groups was determined.
The primary endpoint concerns dose-limiting toxicities and other serious or non-serious toxicities related to intervention, assessed up to 42 days post-treatment. Listed secondary outcomes include response rate, local-regional control, progression-free survival, overall survival, and tumor or blood markers. These outcomes describe a broader set of clinical and biological questions, but the registry record does not report their analysis results.
The study start is listed as 2019-09-25, and primary completion as 2023-11-15. Its status is active, not recruiting. The sponsor is the National Cancer Institute (NCI). A sample-size justification, detailed statistical analysis plan, and explanation of the dose-group design are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Dose Escalation
| Stage | Birinapant 2.8 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) |
|---|---|---|---|---|---|
| STARTED | 0 | 3 | 3 | 4 | 3 |
| COMPLETED | 0 | 3 | 3 | 3 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 1 | 0 |
Reasons for not completing this period:
| Reason | Birinapant 2.8 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) |
|---|---|---|---|---|---|
| Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
Dose Expansion
| Stage | Birinapant 2.8 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) |
|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
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 | Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 3 | 3 | 4 | 3 | 13 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 | 3 | 3 | 1 | 10 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 1 | 2 | 3 |
| Age, Continuous | years | 51.33 (46 to 54) | 55.67 (46 to 62) | 63 (53 to 76) | 71 (63 to 78) | 60.46 (46 to 78) |
| Sex: Female, Male: Female | Participants | 1 | 0 | 0 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 2 | 3 | 4 | 2 | 11 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 1 | 0 | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 1 | 2 | 3 | 9 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 | 0 | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 1 | 0 | 0 | 1 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 0 | 0 | 1 |
| Race (NIH/OMB): White | Participants | 2 | 1 | 3 | 3 | 9 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 1 | 0 | 2 |
| Region of Enrollment: United States | participants | 3 | 3 | 4 | 3 | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence of Dose-limiting Toxicities (DLTs) and Grades 1-5 Serious and/or Non-serious Toxicities Related (Except for Unrelated and Unlikely) to Intervention, measured over Up to 42 days post-treatment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | toxicities |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint combines the incidence of dose-limiting toxicities (DLTs) with serious and non-serious toxicities related to the intervention, excluding events classified as unrelated or unlikely to be related. The stated assessment window is up to 42 days post-treatment. Adverse events are to be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The endpoint is intended to describe the safety and tolerability of the birinapant and radiation combination during the specified period.
The DLT definition identifies events that may be attributed to the combination and occur within the stated timeframe. These include any grade 5 toxicity; hematologic toxicity at grade 4 or higher, except lymphopenia; and non-hematologic toxicity at grade 3 or higher, except nausea or vomiting managed with supportive care over 2 weeks. It also includes grade 3 or higher prolonged serum amylase or lipase elevation, aspartate aminotransferase elevation, and/or alanine aminotransferase elevation lasting more than 7 days, and any toxicity that requires birinapant discontinuation for more than 2 weeks.
In general, a DLT endpoint is useful in an early-phase study because it focuses attention on serious or treatment-limiting events when assessing a regimen and dose. It is not, by itself, a measure of whether a treatment improves cancer outcomes. The registry record does not report the number or incidence of DLTs, nor a numerical result for the full primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a safety-focused primary endpoint but does not report its result. In particular, it gives no numerical count or incidence of DLTs and no complete result for the primary endpoint’s related serious and non-serious toxicities. Consequently, the endpoint cannot be interpreted as establishing a dose level or quantifying the overall safety profile from the information recorded.
The adverse-event summaries provide counts by listed birinapant dose group. At 5.6 mg/m^2, serious adverse events are reported for 1 among 3 at risk, other adverse events for 3 among 3 at risk, and deaths as 0. At 11 mg/m^2, serious adverse events are reported for 3 among 3 at risk, other adverse events for 3 among 3 at risk, and deaths as 1. At 17 mg/m^2, serious adverse events are reported for 1 among 4 at risk, other adverse events for 3 among 4 at risk, and deaths as 0. At 24 mg/m^2, serious adverse events are reported for 1 among 3 at risk, other adverse events for 2 among 3 at risk, and deaths as 0. These are descriptive counts, not estimates from a randomized comparison.
The listed serious adverse-event terms each have a reported percentage of 33.3%: aspiration, cardiac arrest, dehydration, hyponatremia, hypotension, and metabolism and nutrition disorders - Other, iron deficiency anemia. The registry record does not explain the denominator for these percentages or connect each listed term to a particular dose group in the term summary. The terms should therefore not be read as group-specific rates or as proof of causation.
Even when counts are reported by dose, an apparent difference between groups cannot be taken as a dose-response relationship from this design. The record does not describe random assignment, and the groups are not presented as a like-for-like control comparison. The reported counts also do not substitute for the primary endpoint result: serious or other adverse-event summaries are not necessarily identical to the endpoint’s treatment-related toxicity definition or its DLT criteria.
For outcomes such as response rate, local-regional control, progression-free survival, overall survival, and biomarkers, the registry lists measures but does not report numerical findings. No confidence intervals, hypothesis tests, or analysis estimates are reported in the registry record. The appropriate reading is therefore limited to the study’s planned questions and the descriptive adverse-event counts that are available, without concluding that the regimen does or does not produce a clinical benefit.
9. Statistical Methods Explained
The trial is identified as Phase I and single-group. In general, an early-phase study can focus on describing toxicity and examining dosing rather than estimating a comparative treatment effect. Here, the registered primary endpoint is incidence of DLTs and related serious or non-serious toxicities within the stated follow-up window. The registry record does not report a detailed statistical analysis plan, a sample-size justification, or inferential results for that endpoint.
What does a single-group design allow?
In a single-group study, outcomes are described among people receiving the study regimen. Without a separate control group, the design cannot isolate the regimen’s effect from the course of disease, other care, or differences in participant characteristics. The listed dose groups do not remove this limitation: the registry does not identify them as randomized, like-for-like comparisons. Differences in counts across dose groups are descriptive and should not be treated as causal evidence that dose produced a difference.
General statistical interpretation also depends on the outcome’s definition and observation period. The primary endpoint’s timeframe is up to 42 days post-treatment, while the event definition includes specific grade thresholds and exceptions. A count outside that precise definition would not automatically be a DLT. The registry record does not give a primary endpoint count, so the criteria can be explained but not applied to calculate an endpoint result.
How should the adverse-event counts be read?
In general, an at-risk count identifies the group used as the denominator for a reported adverse-event summary, while an affected count indicates how many people were recorded as affected under that summary. The registry lists both counts for serious and other adverse events at each dose group. These are counts, not estimates adjusted for length of follow-up. Person-time, exposure-adjusted rates, and details on recurrent events are not reported in the registry record. A person can also experience more than one event, so event terms and affected-person counts should not be assumed to be interchangeable.
The registry’s serious adverse-event terms are accompanied by percentages of 33.3%, but the term list does not state its denominator or assign terms to particular dose groups. General statistical practice requires a clear denominator to interpret a percentage as a rate. Without that detail, the terms and percentages can be reported as recorded, but they cannot be reliably used to compare groups or estimate a trial-wide incidence.
What do uncertainty and hypothesis tests add?
In general, a confidence interval describes a range of values compatible with an estimate under the statistical model used. Narrow intervals indicate greater precision than wide intervals, but an interval does not remove design limitations or establish causation. A hypothesis test summarizes how compatible the data are with a specified null hypothesis under its assumptions; it does not measure clinical importance. The registry record reports no confidence intervals or hypothesis tests for the primary or secondary outcomes, so there is no basis for describing statistical significance or precision of an effect.
The sample-size assumptions describe planning illustrations based on a stated fraction of an observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation; time-to-event planning uses a total event count. Such calculations are planning scenarios, not observed power and not evidence of a result. They are distinct from the study’s registered enrollment and do not establish that the trial was designed to detect a particular clinical effect. The detailed sample-size justification for the trial is not reported in the registry record.
Why can over-dispersion matter?
In general, count outcomes may vary more than a simple statistical model expects. This is called over-dispersion. If it is present and ignored, standard errors can be too small and confidence intervals too narrow, making results appear more precise than they are. This concept may matter when analyzing event counts, especially if some people experience repeated events. However, the registry record does not report an analysis of over-dispersion or a model for repeated events. It would be inappropriate to claim that either was used or needed for the posted summaries.
The listed secondary outcomes include response rate, local-regional control, progression-free survival, overall survival, and several marker and feasibility outcomes. For time-to-event measures, general analysis may account for censoring, which occurs when an event has not been observed by the last available follow-up. The registry record does not report analysis methods, follow-up distributions, censoring details, or estimates for these outcomes. The presence of a listed outcome alone does not indicate that it was analyzed or that a result was obtained.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes, including response rate, local-regional control, progression-free survival, overall survival, several tumor or blood marker questions, and feasibility of detecting pharmacodynamic effects. When many outcomes are examined, the chance of obtaining at least one apparently notable result by chance can increase. In general, prespecified testing priorities or multiplicity adjustments can help readers understand how a family of tests is interpreted. The registry record does not report a multiplicity strategy or identify a hierarchy for interpreting secondary outcomes.
The record lists 14 outcome measures and 0 analyses. It does not report numerical results or analysis populations for the primary and secondary outcomes. The sample-size justification, analysis-set definitions, and a detailed statistical plan are not reported in the registry record. Thus, it is not possible to determine from the record whether each enrolled participant was included in an endpoint analysis or whether the analysis population differed across outcomes.
Missing-data handling is also not reported in the registry record. In general, missing outcomes can affect estimates if the likelihood of missingness is related to participant characteristics or outcomes. For time-to-event outcomes, the way follow-up ends and participants are censored is important; those details are not reported. No assumptions about missingness, imputation, censoring, or sensitivity analyses should be attributed to this study from the record alone.
Because there is no randomized comparator and no reported inferential analysis, multiplicity adjustments would not resolve the main limits on comparative interpretation. The registry’s outcome list describes questions of interest, not evidence that all were analyzed or that any reported association is confirmatory.
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 |
|---|---|---|---|
| Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | 1 | 3 | 33.3% |
| Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | 3 | 3 | 100.0% |
| Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | 1 | 4 | 25.0% |
| Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | 1 | 3 | 33.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | 0 of 3 |
| Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | 1 of 3 |
| Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | 0 of 4 |
| Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | 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 |
|---|---|
| Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | 3 of 3 |
| Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | 3 of 3 |
| Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | 3 of 4 |
| Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | 2 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) |
|---|---|---|---|---|---|
| Syncope | Nervous system disorders | 0 of 3 | 1 of 3 | 1 of 4 | 0 of 3 |
| Aortic valve disease | Cardiac disorders | 0 of 3 | 0 of 3 | 1 of 4 | 0 of 3 |
| Aspiration | Respiratory, thoracic and mediastinal disorders | 0 of 3 | 1 of 3 | 0 of 4 | 0 of 3 |
| Cardiac arrest | Cardiac disorders | 0 of 3 | 1 of 3 | 0 of 4 | 0 of 3 |
| Dehydration | Metabolism and nutrition disorders | 1 of 3 | 0 of 3 | 0 of 4 | 0 of 3 |
| Hyponatremia | Metabolism and nutrition disorders | 1 of 3 | 0 of 3 | 0 of 4 | 0 of 3 |
| Hypotension | Vascular disorders | 1 of 3 | 0 of 3 | 0 of 4 | 0 of 3 |
| Metabolism and nutrition disorders - Other, Iron deficiency anemia | Metabolism and nutrition disorders | 0 of 3 | 0 of 3 | 0 of 4 | 1 of 3 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Progressive disease | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 3 | 0 of 3 | 0 of 4 | 0 of 3 |
| Pharyngeal stenosis | Gastrointestinal disorders | 0 of 3 | 0 of 3 | 0 of 4 | 1 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Birinapant 5.6 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 11 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 17 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) | Birinapant 24 mg/m^2 & Intensity Modulated Re-Irradiation Therapy (IMRRT) 2 Gray(Gy) |
|---|---|---|---|---|---|
| Lymphocyte count decreased | Investigations | 3 of 3 | 3 of 3 | 2 of 4 | 1 of 3 |
| Dysphagia | Gastrointestinal disorders | 2 of 3 | 1 of 3 | 3 of 4 | 0 of 3 |
| Mucositis oral | Gastrointestinal disorders | 2 of 3 | 2 of 3 | 2 of 4 | 0 of 3 |
| Dermatitis radiation | Injury, poisoning and procedural complications | 1 of 3 | 3 of 3 | 1 of 4 | 0 of 3 |
| Sore throat | Respiratory, thoracic and mediastinal disorders | 1 of 3 | 3 of 3 | 1 of 4 | 0 of 3 |
| Constipation | Gastrointestinal disorders | 2 of 3 | 1 of 3 | 0 of 4 | 1 of 3 |
| Cough | Respiratory, thoracic and mediastinal disorders | 2 of 3 | 2 of 3 | 0 of 4 | 0 of 3 |
| Oral pain | Gastrointestinal disorders | 1 of 3 | 2 of 3 | 1 of 4 | 0 of 3 |
| Dizziness | Nervous system disorders | 2 of 3 | 1 of 3 | 0 of 4 | 0 of 3 |
| Dry mouth | Gastrointestinal disorders | 0 of 3 | 2 of 3 | 1 of 4 | 0 of 3 |
Serious events with the highest arm-level rate: aspiration (33.3%), cardiac arrest (33.3%), dehydration (33.3%), hyponatremia (33.3%), hypotension (33.3%).
The safety summaries report serious adverse events, other adverse events, and deaths separately for the listed birinapant dose groups. For example, at 11 mg/m^2, serious adverse events are reported for 3 among 3 at risk, other adverse events for 3 among 3 at risk, and deaths as 1. At 5.6 mg/m^2, the corresponding entries are 1 among 3, 3 among 3, and 0. At 17 mg/m^2, they are 1 among 4, 3 among 4, and 0; at 24 mg/m^2, they are 1 among 3, 2 among 3, and 0. These are descriptive summaries and do not establish that an event was caused by treatment.
The primary endpoint has a narrower attribution rule: it concerns toxicities related to intervention, excluding events considered unrelated or unlikely to be related, and includes specified DLT criteria. The adverse-event summaries should not be assumed to use exactly that same definition. The registry does not provide enough detail to equate all serious events with DLTs or with treatment-related events. It also does not state whether the reported death was related to treatment.
The serious-event term list reports aspiration, cardiac arrest, dehydration, hyponatremia, hypotension, and iron deficiency anemia within a metabolism and nutrition disorders category, each with a percentage of 33.3%. The denominator and dose-group attribution for these percentages are not reported in the registry record. These terms should be read as descriptive entries, not as comparative rates.
12. What the Result Does, and Does Not, Mean
The posted record describes a Phase I study of birinapant combined with IMRRT, with safety and dose-limiting toxicity as the primary focus. It gives the treatment schedule, a 42-day post-treatment endpoint window, and descriptive adverse-event counts for the listed dose groups. This information can help readers understand what the trial set out to assess and what adverse-event summaries were recorded.
The record does not report a numerical result for the primary endpoint. It therefore does not establish how many DLTs occurred, the incidence of related toxicity under the full endpoint definition, or which dose level was selected. The listed serious adverse-event counts and terms are not substitutes for those missing results, and the record does not establish that any specific event was caused by the regimen.
The single-group structure also limits conclusions about benefit. There is no separate control group in the registry description, and the dose groups are not identified as randomized comparisons. Even if outcomes were reported for each dose, a contrast between groups would not by itself show that dose caused the observed difference. The registry does not report numerical results for response, local-regional control, progression-free survival, overall survival, or the marker outcomes.
In general, a study’s statistical interpretation depends on estimates, uncertainty, outcome definitions, and design. Here, the registry record contains no reported confidence intervals or hypothesis tests for the outcomes. That absence means the precision of any clinical effect cannot be assessed from the record. It does not mean that an effect is absent; it means that the relevant result is not reported in the registry record.
The appropriate conclusion is bounded: this record describes an early-phase combination regimen and records selected adverse-event summaries, but it does not provide the primary endpoint result or clinical outcome estimates needed to judge efficacy, comparative safety, or precision.
13. Why This Trial Matters Statistically
This trial raises a statistical question common to early-phase combination studies: how should toxicity be described when a drug is given alongside re-irradiation? The primary endpoint is structured around DLTs and other related toxicities, with a defined follow-up window and grading criteria. Those details matter because a safety conclusion depends not just on a count, but on which events qualify, whether they are attributed to intervention, and when they occur.
The design also matters. A single-group study can characterize events observed during treatment, but it does not provide a randomized control comparison. The dose-group summaries are therefore not a basis for attributing differences to birinapant dose. Recognizing that distinction helps prevent descriptive counts from being overread as comparative evidence.
The registry lists clinical outcomes and biological markers alongside the primary safety question. This breadth can be useful for framing later research, but it also makes clear why analysis plans and outcome reporting matter. Without reported estimates, uncertainty measures, missing-data methods, and multiplicity procedures, readers cannot assess the strength or precision of findings across those outcomes.
Finally, the posted record illustrates the difference between registration details and results reporting. It describes treatment and endpoints and includes adverse-event summaries, yet does not report a primary endpoint estimate. Statistical interpretation must follow that boundary: the record supports an account of what was measured and which safety counts were posted, but not a conclusion about treatment effect or a definitive dose comparison.
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 central limitation for statistical interpretation is that the registry record does not report a numerical result for the primary endpoint. It also does not report estimates for the listed secondary outcomes. As a result, readers cannot assess the endpoint incidence, estimate uncertainty, or compare observed clinical outcomes with the questions stated in the record.
The study is described as single-group, with allocation not applicable and no masking. There is no separate control group, and the dose groups are not described as randomized, like-for-like comparisons. Descriptive differences across dose groups may reflect factors other than dose. The registry does not report how participants entered each dose group or other information needed to assess comparability.
The adverse-event term percentages have no reported denominator or dose-group attribution in the term list. The record also does not clarify whether these entries represent people, events, or another summary basis. Exposure-adjusted rates, recurrent-event methods, and follow-up details are not reported. The reported death is not identified as related or unrelated to intervention.
Further limitations include the absence of a detailed statistical analysis plan, sample-size justification, analysis-population definitions, missing-data procedures, multiplicity strategy, and inferential results. These omissions do not prove that such methods were not used; they mean that they are not reported in the registry record. The sample-size planning assumptions should not be mistaken for observed power or a description of the trial’s own design justification.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Birinapant and Intensity Modulated Re-Irradiation Therapy in Treating Patients With Locally Recurrent Head and Neck Squamous Cell Carcinoma — NCT03803774.
- Registry record last updated 2026-08-03; status last verified 2026-07.
- Results first posted 2024-07-23.
- 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 a Phase I, single-group study of birinapant with intensity-modulated re-irradiation therapy in locally recurrent head and neck squamous cell carcinoma. Enrollment is listed as 13; the status is active, not recruiting. Treatment combines weekday IMRRT with intravenous birinapant on days 2 and 9 of each cycle, for up to 2 cycles. The primary endpoint concerns DLTs and related serious or non-serious toxicities up to 42 days post-treatment.
Adverse-event summaries are reported for birinapant dose groups of 5.6 mg/m^2, 11 mg/m^2, 17 mg/m^2, and 24 mg/m^2. The registry record does not report a numerical primary endpoint result, inferential analyses, or estimates for the listed secondary outcomes. The single-group design does not support treating the dose groups as randomized controls.