A Study of Dasatinib, Cetuximab and Radiation With or Without Cisplatin in HNSCC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Dasatinib, Cetuximab and Radiation With or Without Cisplatin in HNSCC (NCT00882583), a randomized phase 1 study. The primary outcome is MTD of Daily Oral Dasatinib in Combination With Cetuximab/RT in Cohort A and Daily Oral Dasatinib in Combination With Cetuximab/Cis or Carboplatin/RT in Cohort B 2. MTD of Daily Oral Dasatinib in Combination With Cisplatin/Cetuximab/RT in Cohort B.

2. Clinical Question

3. Trial Design

This was a phase I, parallel-group trial with no masking, and the registry classifies its allocation as randomized. The study concerned locally advanced squamous cell carcinoma of the head and neck. The registry lists enrollment as 22 and identifies Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins as the sponsor. The recorded start was 2009-07, primary completion was 2016-02, and the status is terminated.

The two named cohorts had different treatment descriptions. Cohort A received dasatinib with cetuximab and radiation. Its disease-stage description includes AJCC stage II (T2N0) and stage III (T1-2N1). Cohort B received dasatinib with cisplatin, cetuximab, and radiation. Its stage description includes stage III and IV disease, although the registry text for that description is incomplete. The study title and objective also refer to cisplatin or carboplatin in Cohort B, while the listed intervention and cohort name specify cisplatin. The intended regimen details are not fully reported in the registry record.

The dose-finding objective was to identify a maximum tolerated dose of daily oral dasatinib in each regimen context. Both arm descriptions include an initial cetuximab run-in: a loading dose on day 1, a maintenance dose on day 8, and dasatinib at a specified dose level from day 8 through day 14. The primary outcome timeframe is the last day of radiation. The registry says the study closed because of slow accrual. It does not report the randomization procedure, the numbers assigned to each cohort, or an allocation ratio. The different cohort eligibility descriptions mean that the registry does not establish a like-for-like treatment comparison.

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.

Before assignment: A total of 22 patients were consented. One patient was a screen failure, one patient withdrew consent before initiating any treatment per protocol and patient was replaced in the run-in period before assignment to Cohort A.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: MTD not reached. Data table reports dosage received by each participant. Study closed to slow accrual.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as MTD of Daily Oral Dasatinib in Combination With Cetuximab/RT in Cohort A and Daily Oral Dasatinib in Combination With Cetuximab/Cis or Carboplatin/RT in Cohort B 2. MTD of Daily Oral Dasatinib in Combination With Cisplatin/Cetuximab/RT in Cohort B, measured over Last day of Radiation.

The primary endpoint concerns the maximum tolerated dose (MTD) of daily oral dasatinib when combined with the other treatments in each cohort. The registry defines MTD using dose-limiting toxicity (DLT): a dose producing DLT in 0–1 out of 6 patients; a dose level lower than one producing DLT in fewer than 2 out of 6 patients; or the dose of 150mg PO QD with a DLT rate below 33%. The stated timeframe is the last day of radiation.

In general, early-phase dose-finding studies use toxicity outcomes to identify a dose level for further study while limiting the risk of unacceptable toxicity. The endpoint is therefore about dose and tolerability, not about estimating whether treatment improves tumor control or survival. It also differs from a conventional efficacy endpoint comparing outcomes between treatment groups.

The registry outcome states “MTD not reached” and says the data table reports dosage received by each participant. It does not report the DLT count at each dose level in the outcome description. As a result, the endpoint record does not permit reconstruction of the dose-finding decision or an independent check of which rule determined the conclusion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies this as a phase I, parallel, unmasked study and labels allocation randomized. These design labels give context, but do not reveal the operational methods. The randomization procedure, allocation ratio, concealment procedures, and any stratification are not reported in the registry record. Masking is listed as none. The trial’s main objective was dose-finding, so its central statistical question differs from the usual question of whether one treatment produces better outcomes than a control.

How does the dose-finding rule work?

The outcome definition uses dose-limiting toxicity and a set of dose-level criteria to define the MTD. In plain terms, the rule relates the observed number of DLTs at a dose to whether that dose can be identified as tolerable under the study’s definition. The registry’s wording includes a rule involving 0–1 out of 6 patients, a rule referring to the dose level lower than one with DLT in fewer than 2 out of 6 patients, and a criterion at 150mg PO QD with a DLT rate below 33%.

These criteria explain what the endpoint was intended to measure, but do not show how participants were assigned to dose levels, whether escalation followed a prespecified algorithm, or how decisions were made when observed toxicity did not fit a simple rule. Those details are not reported in the registry record. The outcome summary also does not give DLT counts by dose, so the endpoint cannot be recalculated from the summary information.

What does “MTD not reached” convey?

It conveys the registry’s reported dose-finding conclusion, not a numerical estimate of an MTD. The result does not identify the highest dose administered, the dose at which a DLT threshold was met, or the degree of uncertainty around any dose decision. The record says the dosage received by each participant appears in a data table, but does not provide those individual details in the outcome narrative. It also says the study closed because of slow accrual. The registry does not establish whether slow accrual alone explains why the MTD was not reached.

What can be inferred from the analysis record?

The registry lists zero analysis entries. This means no statistical analysis results are recorded there; it does not establish that no analyses were conducted outside the registry. No model, adjustment strategy, hypothesis-testing procedure, or confidence interval for a cohort comparison is reported. There is also no reported statistical plan describing how the MTD conclusion was derived from the participant-level dosing and toxicity information.

In general, estimates from small early-phase studies can be imprecise because each observed toxicity may have substantial influence on a dose-level decision. The MTD rule itself is a decision rule, not a test of treatment efficacy. A dose-finding result therefore needs to be interpreted with its dose assignments, toxicity definitions, observation period, and escalation procedure in mind. Those procedural details are not fully reported in this registry record.

Why do allocation and cohort descriptions need care?

The record labels the trial randomized, but Cohort A and Cohort B have different stage descriptions and regimens. The record does not explain whether randomization was between these cohorts, occurred within each cohort across dose levels, or used another scheme. Without that information, the design label cannot justify a direct comparison between the cohorts. In general, randomization supports a causal comparison only when the assignment and comparison being analyzed are clearly specified and the design is respected in the analysis.

The posted primary endpoint is not reduced to a single treatment contrast, and there are no analysis records for a contrast to interpret. Thus, a conventional treatment-effect estimate, its standard error, and its confidence interval are not available. Statistical precision for a comparative effect cannot be assessed from the registry outcome summary.

What does over-dispersion mean in general?

For count outcomes, a model may assume a particular relationship between the mean and variability. Over-dispersion means that the observed variability is greater than the model assumes. In general, ignoring over-dispersion can make uncertainty appear too small. This is a general statistical consideration; the registry does not report a count model, an over-dispersion assessment, or an adjusted analysis for this trial.

The registry includes planning assumptions for a sample-size illustration based on an observed effect, equal allocation, a two-sided significance level of 0.05, and a normal approximation. However, the primary outcome is not a single treatment comparison, and no analysis result is posted from which to interpret a comparative effect. Any planning illustration should be treated as a hypothetical design calculation, not as observed power or as evidence that the trial had adequate power. The registry does not report its original sample-size justification.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity plan. It does not describe a hierarchy of hypotheses, an adjustment for multiple comparisons, or a strategy for controlling the overall type I error rate. Since no statistical analysis entries are recorded, there are no posted hypothesis tests whose multiplicity can be evaluated. The primary objective includes dose-finding questions in two regimen settings, but the registry does not specify how decisions across those settings were coordinated statistically.

Missing-data methods are also not reported. The record does not say how participants who discontinued, missed toxicity assessments, or had incomplete follow-up were handled. The primary outcome timeframe is the last day of radiation, but the registry does not describe rules for participants without an assessment at that time. The reported enrollment field and the cohort-specific safety denominators do not, by themselves, explain participant disposition or outcome availability.

Analysis populations are not defined in the registry record. It does not state whether the endpoint was assessed in all enrolled participants, those who started treatment, those who reached a specified dose, or another population. The allocation is labeled randomized, but the record does not report an intention-to-treat analysis or any alternative population definition. These omissions limit assessment of how participants were included in the primary outcome and safety summaries.

In general, multiplicity and missing-data methods matter because choices about which outcomes, groups, and participants enter an analysis can affect estimates and uncertainty. They are especially relevant when several dose levels or cohorts are involved. No such methods should be assumed for this trial beyond what the registry explicitly records.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute renal failure (16.7%), dehydration (16.7%), hypoxia (14.3%), sepsis (8.3%), thrombocytopenia (8.3%).

The registry safety summary separates Cohort A and Cohort B. For serious adverse events, it lists 7 at risk and 1 affected in Cohort A, and 12 at risk and 5 affected in Cohort B. It also lists 1 death in each cohort. These are descriptive registry counts; the record does not report an adjusted safety comparison between cohorts or establish that events were caused by a study treatment.

For other adverse events, the summary lists 7 at risk and 7 affected in Cohort A, and 12 at risk and 12 affected in Cohort B. The registry does not explain in this summary how “other” events relate to the serious-event listing, or whether participants could appear in multiple event categories. Counts across categories should not be added or treated as mutually exclusive.

The listed leading serious-event terms include acute renal failure (16.7%), dehydration (16.7%), hypoxia (14.3%), Sepsis (8.3%), thrombocytopenia (8.3%), and hypophosphatemia (8.3%). The registry does not provide further detail in this summary about event timing, severity grades, dose level, or whether an event occurred in both cohorts. These figures describe reported safety events and do not by themselves establish comparative risk.

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

The main result is a dose-finding outcome: the registry says that the maximum tolerated dose was not reached. This does not identify a recommended dose, an MTD estimate, or a dose level that can be confirmed from the outcome narrative. The record says participant-level dosage received is reported in a data table, but the primary outcome description does not give DLT counts by dose.

The study examined dasatinib with cetuximab and radiation in one cohort and with cisplatin, cetuximab, and radiation in another. The cohort descriptions differ in disease stage, and the registry does not provide a clear direct comparison of the regimens. The classification of allocation as randomized is not enough to establish a comparative treatment effect without details about what was randomized and how the analysis handled the cohort structure.

No efficacy effect estimate or inferential analysis is posted. The record therefore does not establish whether either regimen improved tumor outcomes, nor does it quantify an effect relative to another treatment. The safety counts and event terms describe what the registry records, but they do not establish causation or comparative safety. The study’s termination and slow-accrual explanation describe its conduct, not the clinical effect of treatment.

In general, a phase I dose-finding result is intended to guide decisions about dose selection, rather than answer a definitive efficacy question. Interpretation depends on the dose-escalation procedure, toxicity definitions, assessment schedule, and available follow-up. Several of these details are not reported in the registry record. The result should therefore be understood as an incomplete dose-finding outcome in the posted record, not as proof that a regimen is effective, ineffective, safe, or unsafe.

13. Why This Trial Matters Statistically

This trial illustrates why the endpoint and the design question must be kept distinct. A phase I MTD objective asks about dose and dose-limiting toxicity. It is not the same as an efficacy comparison, and a registry entry stating that the MTD was not reached does not provide an estimate of a treatment effect. The distinction is important when interpreting trial records that include more than one regimen or cohort.

The study also highlights how cohort definitions affect interpretation. Cohort A and Cohort B had different disease-stage descriptions and different treatment combinations. Although the record labels allocation randomized, it does not explain the assignment process or define a direct cohort comparison. Statistical conclusions should follow the actual design and analysis, not a label considered in isolation.

The record makes clear that the study closed because of slow accrual, while its primary dose-finding outcome remained unresolved. This is a useful reminder that an intended endpoint and an observed conclusion are not necessarily the same: a trial can be designed to identify an MTD without the registry ultimately recording one. Without dose-level DLT counts, escalation details, and analysis methods, readers cannot independently assess how the conclusion arose.

Finally, the safety summary demonstrates the value of examining denominators and event definitions alongside counts and percentages. Cohort-specific summaries are descriptive, and the record does not report a comparative safety model. For biostatisticians and clinical researchers, the trial underscores the need to distinguish a descriptive registry result from a fully specified statistical analysis, and to identify when key design and analysis details are not reported.

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 outcome description does not report dose-specific DLT counts, despite defining the MTD through toxicity criteria at dose levels. The record says dosage received by each participant is tabulated, but does not provide the escalation sequence, the number assessed at each level, or the decision process used to reach “MTD not reached.” That limits independent review of the dose-finding conclusion.

The Cohort B stage description is incomplete in the registry record. The title and objective mention cisplatin or carboplatin in Cohort B, while the named arm and intervention list specify cisplatin. The record does not resolve this wording difference or provide enough complete regimen detail to determine how the treatment was implemented.

The registry labels allocation randomized but does not report the randomization method, what assignment applied to, or the allocation ratio. Cohort descriptions differ, and no comparative analysis is posted. Enrollment is recorded as 22, while the safety summaries report cohort-specific denominators; the registry does not explain participant disposition or the relationship between these figures.

The study is terminated, with slow accrual given as the reason for closure. The registry does not report the original sample-size justification, missing-data methods, analysis populations, multiplicity handling, or a statistical analysis plan. It also does not provide inferential results or a dose-specific account of toxicity in the primary outcome summary. These gaps constrain interpretation of both the MTD conclusion and the safety summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Dasatinib, Cetuximab and Radiation With or Without Cisplatin in HNSCC — NCT00882583.
• Registry record last updated 2019-01-09; status last verified 2019-01.
• Results first posted 2017-02-23.
• 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.

18. Record Summary

This phase I parallel study examined daily oral dasatinib with cetuximab and radiation, with or without cisplatin, in locally advanced head and neck squamous cell carcinoma. The registry labels allocation randomized and masking as none. Its primary objective was to determine the MTD in Cohort A and Cohort B. The outcome timeframe was the last day of radiation, and the registry reports that the MTD was not reached.

The record lists enrollment as 22, sponsor Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, start 2009-07, primary completion 2016-02, and status terminated. The registry says the study closed because of slow accrual. It reports serious and other adverse-event summaries by cohort, but does not post statistical analysis entries. Details of dose escalation, cohort allocation, missing-data handling, and comparative analysis are not reported in the registry record.