Cisplatin With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cisplatin With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer (NCT02196168), a randomized phase 2 study. The primary outcome is Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1.

2. Clinical Question

3. Trial Design

The registry record identifies this as a randomized, triple-masked, parallel phase II trial. It lists cisplatin with WEE1 inhibitor MK-1775 in one arm and cisplatin with placebo in the other. The stated sponsor is the National Cancer Institute. The study began in 2014-03, has a primary completion date of 2016-04, and is marked terminated. The reason for termination is not reported in the registry record.

Enrollment is listed as 6. The posted primary outcome has six participants in the MK-1775 and cisplatin arm, with a response value of 0.0. The placebo and cisplatin arm has zero participants and no outcome value. Thus, although the planned design was a randomized comparison, the posted outcome data do not contain observations from both arms. Randomization and masking describe the design, not proof that a comparative analysis could be performed.

The arm descriptions specify different cisplatin infusion durations, as well as MK-1775 versus placebo. Other treatment scheduling, dose details, eligibility criteria, allocation procedures, and masking roles are not reported in the registry record. The study also lists laboratory biomarker analysis and pharmacological study interventions. These listings do not establish what analyses were completed or what results were obtained.

The record lists several secondary outcomes, including adverse events, pharmacodynamic and predictive biomarkers, overall survival, and progression-free survival. It reports six secondary outcomes posted, but does not provide results for them in the information summarized by the registry record. The trial's termination and small posted enrollment are important context when interpreting the incomplete outcome 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.

Overall Study

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 Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1, measured over Up to 1 year.

The primary endpoint is the number of participants with an overall response, defined as complete response plus partial response using RECIST version 1.1, assessed up to one year. RECIST is a standardized framework for evaluating changes in measurable tumors and other disease findings. A complete response requires disappearance of target lesions. A partial response is defined in the record as a decrease of at least 30% in the sum of target-lesion diameters. The record also describes criteria for stable and progressive disease and for non-target lesions.

Counting participants who meet response criteria gives a binary outcome at the participant level: each person either meets the response definition or does not. This endpoint is used in clinical trials because it captures whether tumor measurements satisfy a prespecified response category. It is not a direct measure of how long response lasts, survival, symptoms, or quality of life. Those outcomes are distinct and require their own definitions and analyses.

The posted value for the MK-1775 and cisplatin arm is 0.0 among six participants. The placebo and cisplatin arm has no participants and no reported value. Consequently, the endpoint cannot establish a relative response result between the planned treatment groups. Further details of endpoint assessment, including review procedures, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General explanation: In a randomized parallel trial, participants are assigned to one of the study arms, and outcomes are compared across those groups. Random assignment is intended to make the groups comparable on average, but it cannot substitute for outcome data. Here, the registry record identifies a randomized parallel design, while the posted primary outcome has participants in only one arm. The intended comparison therefore cannot be estimated from the available arm results.

General explanation: The primary endpoint is binary at the participant level: a person either has a complete or partial response under the stated RECIST criteria, or does not. A two-arm comparison for a binary endpoint can be expressed in different ways, such as an absolute difference in response proportions or a relative measure. Each approach requires outcome data in both groups. With no participants and no outcome value in the placebo arm, a treatment contrast is not estimable from the registry record.

General explanation: A confidence interval describes a range of values compatible with the observed data under a statistical model. It communicates uncertainty, rather than guaranteeing that the true value lies in a particular range. The registry record does not post a confidence interval for the primary outcome. The small number of participants in the arm with results would also make precision an important concern, even if a single-arm interval were available. No interval should be inferred from the count alone.

General explanation: A hypothesis test evaluates data against a specified statistical model and a null hypothesis. A p-value would not repair the lack of comparator observations; a valid two-arm test needs information from both arms. The registry record reports no analyses for the posted outcomes and does not report a primary-outcome test statistic or p-value. The significance level and test procedure for the trial's own primary analysis are not reported in the registry record.

General explanation: A sample-size calculation is a planning exercise based on assumptions about the event rate, effect of interest, variability, significance level, power, allocation, and analysis method. It is different from observed power, which should not be used to summarize the evidential strength of an already observed result. The registry record does not report the trial's original sample-size justification or its design assumptions. Planning illustrations based on an observed effect cannot create a two-arm effect estimate when comparator outcome data are absent. The posted record also notes that values are not estimable for a two-arm binary comparison.

General explanation: Over-dispersion is a concern in some count or rate models when outcomes vary more than the model expects. It is not a basis for interpreting this endpoint: the primary outcome is a binary participant response, and the registry record does not report a model-based estimate. More generally, model choice should follow the outcome type and prespecified analysis plan; that plan is not reported in the registry record.

General explanation: Time-to-event outcomes such as overall survival and progression-free survival require information about event times and censoring, not merely the number of participants with a response. The registry lists these secondary outcomes, but event counts, follow-up summaries, estimates, and analysis details are not reported in the registry record. They therefore cannot be interpreted from the primary response count.

The record describes a masking level of triple, but does not report who was masked or how masking was maintained. It names RECIST version 1.1 for the primary endpoint, but assessment details beyond the criteria are not reported. The analysis population, handling of missing observations, adjustment factors, and statistical methods are also not reported in the registry record. These omissions mean the analysis cannot be reconstructed from the posted information.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Arm I (WEE1 Inhibitor MK-1775, Cisplatin)")
n      <- c(6)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Arm I (WEE1 Inhibitor MK-1775, Cisplatin)  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including adverse events, pharmacodynamic biomarkers, predictive biomarkers, overall survival, and progression-free survival. It does not report a statistical plan for controlling multiplicity across the primary and secondary outcomes. Multiplicity is the issue that arises when several hypotheses or outcomes are examined: without an appropriate plan, interpreting isolated statistical findings can overstate how much evidence they represent. No such findings are available for these secondary outcomes in the posted record.

The registry record does not report how missing outcome data were handled, whether all randomized participants were included in each analysis, or how the analysis populations were defined. These details matter because exclusions or incomplete follow-up can affect which participants contribute to an estimate. The posted primary outcome lists six participants in the MK-1775 arm and zero in the placebo arm; it does not explain why the comparator arm has no participants or whether any participants were randomized but not included in the outcome listing.

The record also does not report an intention-to-treat analysis, a per-protocol analysis, imputation, sensitivity analyses, interim analyses, or stopping rules. Their absence from the record should not be taken as proof that they were or were not used. The reason for termination is not reported in the registry record, so no inference about its relationship to missing outcomes or planned analyses is warranted.

Because the primary endpoint has no comparator outcome value, no two-arm estimate can be calculated regardless of how missing data might otherwise be addressed. Any interpretation must remain descriptive and limited to the participants and values posted.

12. Safety Results

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

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: anemia (50.0%), white blood cell decreased (33.3%), neutrophil count decreased (33.3%), generalized muscle weakness (33.3%), febrile neutropenia (16.7%).

For the MK-1775 and cisplatin arm, the registry reports six participants at risk for other adverse events and six affected. For serious adverse events, six were at risk and four were affected. The placebo and cisplatin arm has zero participants at risk and zero affected in the posted safety groups, so it offers no enrolled comparison group for interpreting these figures.

The listed serious adverse-event terms and percentages are anemia, 50.0%; white blood cell decreased, 33.3%; neutrophil count decreased, 33.3%; generalized muscle weakness, 33.3%; febrile neutropenia, 16.7%; and lymphocyte count decreased, 16.7%. These are registry-listed terms and percentages; the record does not give additional detail about event timing, recurrence, severity grading, or attribution to study treatment.

Serious adverse events and other adverse events are separate summary categories. The figures describe participants recorded in the posted arm, not a comparison of risks between treatment groups. With no participants in the placebo arm, the record cannot establish whether these events were more or less frequent under one assigned regimen than the other. The registry does not report deaths for either arm in these safety summaries.

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

The primary outcome result is a count: zero participants with a complete or partial response is posted for the MK-1775 and cisplatin arm among six participants. No outcome value is posted for the placebo and cisplatin arm because that group has zero participants in the outcome record. This establishes what the registry reports, but it is not a comparative estimate.

The result does not show whether adding MK-1775 changed response relative to cisplatin with placebo. It also does not establish the response probability for a wider population, the duration of any response, survival, or the balance of benefits and harms. Those are separate questions requiring relevant outcome data and appropriate analyses. The record lists some of these as secondary outcomes but does not report results for them in the information summarized.

The study's randomized designation and triple masking are features of its planned design. They do not make the posted outcome comparative when one arm has no participants. Likewise, the terminated status indicates that the study did not remain listed as ongoing, but the reason for termination is not reported in the registry record. No explanation for the incomplete enrollment or absent comparator results should be assumed.

The safety figures provide descriptive counts for the six participants in the MK-1775 arm. They should not be interpreted as evidence that the study regimens differ in safety, since no comparator participants are recorded. Nor do the posted data establish whether an event was caused by a particular treatment.

In short, these results document a limited set of observations from a small, incomplete randomized study. They cannot answer the intended two-arm efficacy question, and they should not be generalized beyond the information actually posted. A lack of comparator data is not evidence of equivalence, benefit, or harm.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it separates a planned design from the data ultimately available for analysis. Randomization and masking are important design features, but they do not guarantee that a useful comparison will be posted. When one arm has no participants, there is no empirical basis for estimating a between-arm outcome contrast, regardless of the sophistication of a statistical method.

The record also illustrates why enrollment and completeness matter when interpreting a binary endpoint. A response count can be described for the arm with observations, but a single-arm count does not answer a randomized comparative question. A reader must distinguish a zero count in one observed group from a claim that the treatment has no effect, and distinguish missing comparator information from evidence that the two groups are alike.

Another statistical lesson is the importance of transparent reporting. The registry gives the study status, arm descriptions, enrollment, and limited primary and safety outcome information, but does not report the reason for termination, original sample-size justification, analysis populations, missing-data methods, or statistical analysis plan. These details shape how estimates should be interpreted and whether analyses can be reproduced.

Finally, the result underscores that a trial's scientific question can remain unanswered even when some outcomes are posted. The registry record can still be informative about what was recorded and about the limits of inference. In this case, careful interpretation means reporting the observed arm data while avoiding a comparative conclusion unsupported by the posted results.

15. 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 main limitation is the absence of participants and an outcome value in the placebo and cisplatin arm. This prevents estimation of the intended two-arm primary endpoint comparison. The posted enrollment is six, with all six listed in the MK-1775 and cisplatin arm, so the outcome data do not represent the planned randomized comparison.

The study is marked terminated, but the reason is not reported in the registry record. The record also does not explain the difference between the overall enrollment listing and the arm-level outcome listings, or whether any participants were randomized but omitted from the reported outcome groups. Missing-data handling and analysis-population definitions are not reported.

The primary result is a count without a confidence interval or a reported statistical test. The trial's original sample-size justification, primary analysis plan, outcome assessment procedures, and timing of primary assessment for each participant are not reported. The stated timeframe is up to one year, but participant-level follow-up completeness is not reported.

Secondary outcomes are listed, but their numerical results and analysis methods are not reported in the registry record. Safety details are limited to the posted participant counts and serious-event terms; event-level timing, severity grading, treatment attribution, and additional context are not reported. Masking is described as triple, but the roles masked and procedures are not described.

These limitations constrain both precision and interpretation. They do not establish why the study ended or what its complete results might have been. Conclusions should remain limited to the recorded observations.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cisplatin With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer — NCT02196168.
• Registry record last updated 2017-05-03; status last verified 2017-03.
• Results first posted 2017-05-03.
• 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.

19. Record Summary

This randomized, triple-masked, parallel phase II trial evaluated cisplatin with WEE1 inhibitor MK-1775 versus cisplatin with placebo for recurrent or metastatic head and neck squamous cell cancer. The study is sponsored by the National Cancer Institute and is marked terminated.

The posted primary outcome is overall response under RECIST version 1.1 up to one year. The MK-1775 and cisplatin arm lists six participants and a response value of 0.0. The placebo and cisplatin arm lists zero participants and no outcome value, so a comparative result is not estimable from the posted data.

Safety summaries report six participants at risk for other adverse events and four at risk with serious adverse events in the MK-1775 arm; the placebo arm has no participants. The termination reason, trial-specific statistical plan, missing-data approach, and results for the listed secondary outcomes are not reported in the registry record.