Pembrolizumab and Vorinostat in Treating Patients With Recurrent Squamous Cell Head and Neck Cancer or Salivary Gland Cancer That Is Metastatic and/or Cannot Be Removed by Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pembrolizumab and Vorinostat in Treating Patients With Recurrent Squamous Cell Head and Neck Cancer or Salivary Gland Cancer That Is Metastatic and/or Cannot Be Removed by Surgery (NCT02538510), a na phase 1, phase 2 study. The primary outcome is Incidence of Toxicity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0.

2. Clinical Question

This phase I/II study was designed around treatment with the combination, rather than a like-for-like comparison of separate treatment groups. Its primary endpoint concerns toxicity. The registry also lists objective response rate, overall survival, and progression-free survival as secondary outcomes, but numerical results for those outcomes are not included in the registry record reviewed.

The clinical question therefore has two distinct parts: what safety events were recorded during the study, and what evidence is available about tumor response or time-to-event outcomes? The posted safety figures give counts by cancer group, but they do not supply the primary endpoint's complete results. In particular, the registry's primary endpoint description says toxicities would be summarized by type and percentage, while the available record does not give those endpoint values. The tables and plots can help organize the posted information, but they cannot fill gaps in the registry record.

Because there is no concurrent control group, this study cannot estimate a randomized contrast between the combination and another treatment. Its results should instead be read as observations from participants treated within this study, with the limitations that follow from a single-group design and the information actually posted.

3. Trial Design

This is a single-group phase I/II study sponsored by the University of Washington. The registry records an enrollment of 50 and describes participants with recurrent, unresectable and/or metastatic squamous cell head and neck cancer or salivary gland malignancies. The study began on 2015-10-08, reached primary completion on 2019-09-28, and is listed as completed.

Participants received vorinostat by mouth or via PEG on days 1-5 and pembrolizumab intravenously over 30 minutes on day 1. Courses were scheduled to repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Laboratory biomarker analysis is also listed as an intervention, but the registry record does not describe a biomarker endpoint result.

The study is listed as having no masking and no randomized allocation. Its single-group structure matters when reading the posted data: there is no separate control group against which to estimate a treatment contrast. The registry's safety data are presented under two disease-group labels, Head and Neck Squamous Cell Carcinoma and Salivary Gland Carcinoma. These labels do not turn the study into a randomized comparison; they identify the groups used in the posted adverse-event information.

The primary outcome is incidence of toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The stated timeframe extends to 30 days after completion of study treatment. The registry says that only grade 3 toxicities and toxicities requiring a dose hold or reduction were recorded for this primary outcome. It also lists objective response rate, overall survival, and progression-free survival as secondary outcomes. The specific statistical plan, sample-size justification, and interim-analysis procedures are not reported in the registry record.

Although the record is marked completed, that status alone does not mean that all planned outcomes or analyses are available. The posted data include safety figures, but the primary endpoint results and numerical secondary-outcome findings 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Only G3 toxicities and toxicities requiring dose hold/reduction recorded.

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: RMHNSCC with the following primary sites:nasopharynx, paranasal sinus, nasal cavity, skin/cutaneous sites. Pts with unknown HN primary sites will be enrolled. Patients with biopsy proven RMSGC be eligible as well

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Toxicity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0, measured over Up to 30 days after the completion of study treatment.

The primary endpoint counts participants with specified toxicities. The registry describes the outcome as incidence of toxicity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0, with a timeframe extending up to 30 days after study treatment ends. The endpoint description says the planned summaries were the number and percentage of participants with each type of toxicity. The population description narrows what was recorded: only grade 3 toxicities and toxicities requiring a dose hold or reduction.

As a general statistical concept, a participant count is a straightforward way to describe how often a defined event was observed in a study group. A percentage can help express that count relative to the number assessed, but interpretation still depends on which events qualify, how completely participants were followed, and which participants were included in the analysis. Here, the registry does not include the complete primary endpoint count-and-percentage summaries, so the endpoint cannot be evaluated in full from this record.

Safety is a relevant endpoint in a phase I/II study of a drug combination because it describes observed toxicities during treatment and the specified follow-up period. It does not by itself establish comparative safety: this study has no separate control group. Nor should the recorded toxicities be treated as a complete account of every possible adverse event, because the primary outcome's population description restricts recording to the specified severity and dose-management criteria.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record gives a single-group phase I/II design and descriptive safety information. It does not report the detailed statistical analysis plan, sample-size justification, interim analyses, or analysis populations beyond the description attached to the primary endpoint. The concepts below explain how such information is generally interpreted; they are not claims about procedures used in this study.

What does a single-group design estimate?

Generally, a single-group study describes outcomes observed among participants who receive the study regimen. It does not create a concurrent untreated or alternative-treatment group. As a result, a count of events or responses can describe what was recorded in this cohort, but it cannot by itself isolate the effect of treatment from other influences. Comparisons with another study or external population would require careful attention to differences in eligibility, follow-up, measurement, and clinical context. Such a comparison is not reported in the registry record.

Here, the registry lists no randomized allocation and no masking. These design features should be interpreted alongside the single-group structure. The disease-group headings in the adverse-event information describe participant categories, not randomized comparisons of different interventions.

What does a participant count show?

Generally, a count reports the number of participants meeting a defined event criterion. A count depends on the event definition and on who was observed and assessed. A proportion adds a denominator, but a proportion is meaningful only when the numerator and denominator refer to the same population and observation rules. A confidence interval can communicate uncertainty around an estimated proportion; wider intervals usually indicate less precision, while narrower intervals indicate greater precision under the chosen method. The registry record does not include confidence intervals for the outcomes.

The primary endpoint's definition is particularly important. The record says only grade 3 toxicities and toxicities requiring a dose hold or reduction were recorded. This makes the primary outcome narrower than an accounting of all adverse experiences. The adverse-event section separately reports serious and other adverse-event figures. These categories should not be assumed to match the primary endpoint's definitions without a stated crosswalk, which is not reported in the registry record.

How should event categories be read?

Generally, serious adverse events and other adverse events are different reporting categories, and the number of participants affected is not the same as the number of individual events. A participant may experience more than one event, depending on the registry's counting rules. The record gives participant counts for the displayed categories and top serious terms, but does not report enough detail to reconstruct event-level histories or determine overlap between categories.

The named serious terms are useful as signals of which types of events appear among the reported entries. They are not a complete list of all possible events, and they do not establish cause. Attribution to a treatment requires information about timing, clinical assessment, and the study's event-classification rules. Those details are not reported.

What can a planning illustration tell us?

Generally, a sample-size calculation describes how many participants might be needed under stated assumptions to detect a chosen effect with a specified statistical procedure. It is a planning exercise, not evidence that a study had that power, and it does not describe the certainty of results after the study has been completed. The sample-size section is identified as an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. For time-to-event outcomes, the stated convention is to show the total number of events; for other outcomes, it is participants per arm. Those assumptions do not describe this trial's single-group design.

The registry record does not report the study's own sample-size justification. The planning illustration should therefore be kept separate from the trial design and should not be read as a trial protocol or as observed power. Power is a design-stage probability under assumptions; it is not a measure of how convincing the posted results are.

What does an unreported analysis mean?

Generally, a missing analysis result cannot be treated as a null result. It may reflect incomplete registry reporting, an analysis not posted in that record, or another reason that cannot be identified from the information. The registry lists four outcome measures and no analysis records. That means the detailed analyses are not reported in the registry record reviewed; it does not establish that no analyses were conducted.

For this study, the most defensible statistical reading is descriptive: report the posted counts and their categories, distinguish them from the primary endpoint's full summaries, and avoid claims that require a control group, inferential analysis, or numerical efficacy outcomes that are not present.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, including the primary toxicity endpoint and secondary outcomes of objective response rate, overall survival, and progression-free survival. The record does not report a multiplicity strategy, such as how interpretation would account for examining several outcomes. In general, multiplicity matters because repeated statistical tests can increase the chance of at least one apparently notable result occurring by chance. Without a stated plan and posted analyses, it is not possible to determine how this issue was handled.

Missing-data methods are also not reported in the registry record. The record does not describe how participants with incomplete follow-up, missed assessments, treatment discontinuation, or unavailable outcome measurements were handled in the analyses. It would be inappropriate to assume that all enrolled participants were included in every outcome analysis or that a particular imputation method was used.

The primary endpoint population description says that only grade 3 toxicities and toxicities requiring a dose hold or reduction were recorded. It does not specify a broader analysis population or explain how incomplete event reporting was addressed. The detailed statistical analysis plan and analysis populations are not reported in the registry record. Consequently, the posted counts should be interpreted within their stated event definitions, without assuming a particular intention-to-treat, per-protocol, or safety population.

The record lists no analysis records, and numerical results for the primary endpoint and secondary efficacy outcomes are not included. That reporting gap prevents assessment of the planned analysis, the handling of missing observations, and the precision of outcome estimates. It should not be mistaken for evidence that no analyses took place.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: adrenal insufficiency (4.0%), pneumonitis (4.0%).

The registry lists safety figures separately for Head and Neck Squamous Cell Carcinoma and Salivary Gland Carcinoma. For each group, 25 participants are listed as at risk for serious adverse events and 1 as affected. For other adverse events, 25 are listed as at risk in each group; 11 are affected in the Head and Neck Squamous Cell Carcinoma group and 19 in the Salivary Gland Carcinoma group. The record also lists 22 deaths and 23 deaths, respectively. These are registry counts and should not be interpreted as treatment effects or as comparisons between randomized arms.

Adrenal Insufficiency and Pneumonitis are the two top serious terms shown, each at 4.0%. The record does not provide enough detail to establish whether these events were attributed to treatment, when they occurred, or whether a participant could appear in more than one category. Counts of participants affected are not necessarily counts of individual event episodes.

These figures are distinct from the primary endpoint description, which records only grade 3 toxicities and toxicities requiring a dose hold or reduction. The registry does not provide the complete primary endpoint summaries. The safety numbers are therefore best read as the posted adverse-event information, with the stated categories and denominators, rather than as a comprehensive account of all toxicity or a causal assessment.

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

The posted record documents a completed, single-group phase I/II study of pembrolizumab with vorinostat and includes adverse-event counts for two disease groups. It also identifies the primary safety question and the secondary outcomes selected for the study. These details are useful for understanding what the investigators set out to examine and what safety information appears in the registry.

The record does not include the full primary endpoint results or numerical findings for objective response rate, overall survival, or progression-free survival. It therefore does not allow a complete assessment of the study's primary safety outcome or its secondary efficacy outcomes. A completed status does not fill in results that are absent from the registry record.

The adverse-event counts should not be taken as proof that the combination caused the events, nor as evidence about how its safety compares with another regimen. A single-group study lacks a randomized comparator, and the posted disease-group categories are not treatment arms. Likewise, the listed deaths cannot be interpreted as a treatment effect from these figures alone; the record does not provide the information needed to establish their timing, cause, or relation to treatment.

In general, statistical interpretation depends on both the point estimate and its precision. Here, the registry does not report confidence intervals or full outcome analyses for the results described. The observed counts can be quoted as posted, but they do not by themselves establish how precisely underlying event rates are known. Nor can missing numerical efficacy results be taken to mean that no response or survival information was collected.

The appropriate conclusion is limited: the record describes the study design and posts selected safety figures, but does not report enough numerical outcome information to draw a complete statistical account of safety or efficacy. The study's findings should not be expanded beyond what is actually reported.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a study's question and the results that are available for analysis. Its primary outcome was toxicity, with recording restricted to grade 3 events and events requiring a dose hold or reduction. That definition shapes what the endpoint can show: it is not a complete inventory of all adverse experiences. Reading the endpoint definition before interpreting a result is essential in any clinical study.

The single-group design also sets a clear boundary on inference. The study can describe participants treated with the combination, but it does not provide a randomized comparison against another regimen. The two disease-group labels in the safety record do not change that design. This distinction prevents descriptive subgroup entries from being mistaken for comparative treatment evidence.

Another important statistical issue is reporting completeness. The registry identifies secondary outcomes but does not include numerical findings for them, and it does not give the primary endpoint's full count-and-percentage summaries. A record can be marked completed while still leaving important analyses unavailable to readers. Outcome definitions, denominators, missing-data handling, and uncertainty measures all affect how results can be interpreted.

Finally, planning calculations and observed results answer different questions. A sample-size illustration based on stated assumptions is not a description of the study's design justification and is not observed power. Keeping planning assumptions separate from the trial's actual single-group design helps avoid a common interpretive error. This record is a useful example of why statistical conclusions must follow the design and the information actually posted.

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 main limitation for interpreting this particular record is that the primary endpoint's complete results are not reported. Although the endpoint is defined as participant counts and percentages by toxicity type, the record does not give those summaries. The posted safety figures therefore cannot stand in for the full primary endpoint analysis.

The registry lists objective response rate, overall survival, and progression-free survival as secondary outcomes, but does not report their numerical results. It also does not report confidence intervals, detailed analysis populations, missing-data procedures, multiplicity handling, or a statistical analysis plan. These omissions limit assessment of both the estimates and the methods used to produce them.

The single-group design has no randomized control group, so the posted event counts do not support a controlled comparison. The two disease-group labels should not be read as intervention groups. The record also does not provide detailed event-level information, including timing and treatment attribution, so the adverse-event entries cannot establish causation or explain the listed deaths.

Finally, the primary toxicity endpoint has a restricted recording definition: only grade 3 toxicities and toxicities requiring a dose hold or reduction are described as recorded. It should not be interpreted as covering every toxicity. The record does not report the study's sample-size justification, interim-analysis procedures, or the rationale for the enrolled population. These trial-specific gaps constrain conclusions beyond the descriptive information posted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pembrolizumab and Vorinostat in Treating Patients With Recurrent Squamous Cell Head and Neck Cancer or Salivary Gland Cancer That Is Metastatic and/or Cannot Be Removed by Surgery — NCT02538510.
• Registry record last updated 2024-11-26; status last verified 2024-11.
• Results first posted 2020-10-22.
• 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 University of Washington study is listed as a completed, single-group phase I/II trial of pembrolizumab and vorinostat for recurrent, unresectable and/or metastatic squamous cell head and neck cancer or salivary gland malignancies. Enrollment is listed as 50. The study began on 2015-10-08, with primary completion on 2019-09-28.

The primary endpoint concerns specified toxicities through up to 30 days after study treatment, including only grade 3 toxicities and those requiring a dose hold or reduction. The registry lists objective response rate, overall survival, and progression-free survival as secondary outcomes. It posts adverse-event counts for two disease groups, but does not report the complete primary endpoint summaries or numerical secondary-outcome findings in the record reviewed.

The design has no randomized control group. The available counts are descriptive and cannot establish comparative effects or causation. The registry record does not report the detailed analysis plan, sample-size justification, or missing-data procedures.