A Study of a New Combination and Schedule of Chemotherapy Drugs for the Treatment of Head and Neck Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of a New Combination and Schedule of Chemotherapy Drugs for the Treatment of Head and Neck Cancer (NCT00148122), a na phase 2 study. The primary outcome is Overall Response Rate at 4 Months.

2. Clinical Question

3. Trial Design

This was a Phase II, single-group trial of docetaxel and capecitabine in patients with metastatic or advanced, locally recurrent head and neck cancer. The registry records 40 enrolled patients. The study began in 2002-11, had primary completion in 2008-08, and is marked completed. The sponsor is University of Michigan Rogel Cancer Center.

With one treatment group and no masking, the design can describe outcomes among participants receiving the combination, but it does not provide a concurrent control group for estimating a treatment contrast. The registry lists allocation as NA. Thus, there is no randomized allocation between study arms to interpret, and the single arm should not be treated as if it were one side of a randomized comparison.

The arm description gives a schedule for both drugs. The registry summary characterizes the study purpose as assessing effectiveness and side effects of a new combination and schedule. The primary endpoint was overall response rate at 4 months. The listed secondary outcomes were frequency of Grade III/IV toxicities and probability of progression-free survival. Although three outcome measures are recorded, the registry lists no analysis entries.

The response population description states that 2 patients withdrew consent and 2 were not evaluable according to protocol criteria. It says response evaluability required receiving at least 2 cycles of chemotherapy or having obvious clinical signs of progression on physical examination; the text describing the latter condition is incomplete in the registry record. The available information therefore does not fully specify how every enrolled participant was handled in the primary endpoint analysis.

No comparator group, masking, or analysis entries are recorded. Details of a statistical analysis plan, including any model, adjustment, or prespecified decision rule, are not reported in the registry record. Design features should therefore be interpreted from the information actually recorded, not from assumptions about how Phase II studies are usually conducted.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 40 patients were enrolled. 2 patients withdrew consent and 2 patients were not evaluable per protocol criteria: A patient will be considered evaluable for response if they received at least 2 cycles of chemotherapy, OR if they have obvious clinical signs of disease progression on physical examination after one cycle of chemotherapy.

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: Although 40 patients were enrolled, 2 patients withdrew consent after treatment started, therefore only 38 were included in baseline analysis.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate at 4 Months, measured over 4 months.

The primary endpoint, overall response rate at 4 months, is the percentage of participants classified as having a complete or partial response at that assessment. The registry says disease was assessed by radiologic imaging and response was determined using RECIST. Under the stated definition, complete response means disappearance of all target lesions; partial response means at least a 30% decrease in the sum of the longest diameter of target lesions. Overall response combines those two categories.

Response rate is a binary-outcome summary: each assessed participant is classified as having or not having a response under the criteria. General: this kind of endpoint can provide a clear description of tumor shrinkage meeting a specified rule at a specified assessment time. It does not, by itself, describe how long a response lasts or whether disease later progresses. The registry separately lists probability of progression-free survival as a secondary outcome, but does not provide its result.

The 4-month timing matters because response status is tied to an assessment point. The record does not state how timing deviations, missing imaging, or participants who were not evaluable were incorporated into an analysis. Most importantly, it does not report the observed response percentage, response count, or an uncertainty interval. The endpoint definition is available, but its numerical result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary percentage endpoint: overall response at 4 months. General: a binary endpoint assigns each participant to one of two broad outcome categories, such as response or no response, according to a prespecified definition. The response definition uses imaging and RECIST categories. The resulting response percentage would summarize the fraction of participants in the analyzed population meeting the complete- or partial-response criteria. The actual percentage and analysis denominator are not reported in the registry record, so no estimate can be interpreted.

What does an estimate of response rate describe?

General: an observed response rate is a descriptive estimate for the participants included in its analysis. It is not automatically an estimate of a causal treatment effect. In a single-group study, there is no concurrent control group to distinguish outcomes associated with the study regimen from outcomes that might occur under another treatment or through other influences. The design is therefore suited to describing the enrolled group’s observed outcomes, but it does not establish a comparative effect by itself.

A confidence interval, if reported, would describe statistical uncertainty around an estimated response rate under the assumptions of the method used. General: a narrower interval indicates greater precision, while a wider interval indicates less precision. The registry does not report a confidence interval for the primary outcome, nor does it record the response count or percentage. Precision therefore cannot be evaluated. No significance test or p-value for the primary endpoint is listed.

Why does the response definition matter?

The definition determines which imaging changes count as responses. Complete response is defined as disappearance of all target lesions. Partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions. Combining these categories yields overall response under the registry’s stated rule. In general, explicit criteria promote consistency in classification, but they do not resolve every analytic question. The record does not report how assessments were timed if they differed from the 4-month endpoint, how missing imaging was handled, or whether response assessments were reviewed independently.

The population description says that participants were evaluable if they received at least 2 cycles of chemotherapy or showed obvious clinical signs of progression on physical examination. The latter criterion is cut off in the record. The description also notes 2 withdrawals of consent and 2 participants not evaluable per protocol criteria. It does not provide the complete analysis population definition or explain how those cases were treated in the endpoint calculation. Those omissions prevent reconstruction of the denominator or the handling of incomplete outcome information.

What can the safety counts show?

General: adverse event counts describe events reported in a study population; they do not, without a comparison group and adequate analytic detail, establish that the intervention caused each event. The record lists 25 participants with serious adverse events among 38 at risk and 36 with other adverse events among 38 at risk. Selected serious-event terms are accompanied by percentages. These counts do not supply the missing primary efficacy result. Nor should serious adverse events be assumed to equal the separately named secondary outcome of Grade III/IV toxicities.

Are there design-based planning calculations?

The registry includes assumptions for planning illustrations based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a target effect described as a stated fraction of the observed effect. These are planning assumptions, not a report of the trial’s actual design or an observed-power analysis. The trial itself is listed as single-group, so the hypothetical equal-allocation, two-arm setup does not describe its recorded allocation. The registry does not report a sample-size justification, and no numerical planning result is stated in the record summarized for this analysis.

General: over-dispersion is relevant when observed variability exceeds what a simple statistical model assumes; accounting for it can affect uncertainty estimates. The primary endpoint is a percentage, and the registry lists no dispersion parameter or analysis entries. There is no basis in the record to claim that over-dispersion was present or that a particular model was used. More generally, statistical methods should be interpreted from documented analyses, not inferred from the endpoint type or trial phase.

In short, the record supports explanation of the endpoint definition and the broad distinction between descriptive response and comparative effect. It does not provide the numerical response estimate, interval, test, or full analytic population needed to assess the endpoint statistically.

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 1")
n      <- c(36)
events <- c(6)
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 1  36  6  16.7  6.4  32.8  7.9  31.9  8.0  32.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures: overall response rate at 4 months, frequency of Grade III/IV toxicities, and probability of progression-free survival. It identifies the response rate as primary and the other two as secondary outcomes. The record lists no analysis entries and does not provide results for these measures. Details of any multiplicity strategy, such as whether inference across multiple outcomes was adjusted or which outcomes were considered confirmatory, are not reported in the registry record.

General: when several outcomes are tested, the chance of at least one apparently unusual result can increase if each is assessed separately using conventional thresholds. A prespecified strategy can clarify which outcomes carry the main inferential emphasis and how multiple tests are handled. No such strategy is documented here, so it should not be assumed that an adjustment was or was not used.

Missing-data handling is also not described. The primary outcome population text records 2 consent withdrawals and 2 participants who were not evaluable under protocol criteria, but the available eligibility description is incomplete. The record does not state whether these participants were excluded from the response analysis, counted as nonresponders, or handled another way. It also does not report how missing imaging or other incomplete assessments were handled.

The registry does not define a full analysis population or describe any sensitivity analysis for missing outcomes. Thus, the distinction between enrolled participants, response-evaluable participants, and participants included in any endpoint calculation cannot be reconstructed. These gaps limit both reproducibility and interpretation of any response estimate; in this record, the estimate itself is not reported.

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: dyspnea (7.9%), disease progression (5.3%), hemorrhage-other (5.3%), nausea (5.3%), pulmonary-other (5.3%).

The safety record lists 38 participants at risk for serious adverse events, with 25 affected, and 38 at risk for other adverse events, with 36 affected. These are reported counts for the single study arm. The selected serious adverse event terms and their listed percentages are dyspnea, 7.9%; disease progression, hemorrhage-other, nausea, and pulmonary-other, each 5.3%; and alanine aminotransferase increased, 2.6%.

These figures describe the registry’s safety reporting; they are not a comparison against a control group. The percentages attached to terms should not be added together or read as mutually exclusive categories. The record does not state whether participants could contribute more than one event term, and it does not provide a complete account of event timing, duration, or attribution.

The listed serious-event counts are not a reported result for the secondary outcome of Grade III/IV toxicities. Seriousness and toxicity grade describe different aspects of adverse events, so the categories should not be treated as equivalent. The frequency of Grade III/IV toxicities is named as an outcome, but its result is not reported in the registry record.

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

The registry record establishes that a Phase II, single-group trial evaluated docetaxel and capecitabine in patients with advanced or recurrent head and neck cancer. It specifies an overall response endpoint at 4 months and defines response using imaging and RECIST. It also gives selected safety counts. These details describe the study’s question and some of its recorded safety experience.

The record does not report the primary response result. Without an observed response percentage, response count, or confidence interval, it is not possible to describe the frequency of response or how precisely it was estimated. The outcome definition cannot stand in for the outcome itself. The record also lacks analysis entries, so it does not establish how endpoint estimates or uncertainty were calculated.

Because this was a single-group study, the design does not provide a randomized comparison with another regimen or a control group. Even if an outcome estimate were available, this design alone would not show how outcomes compared with what would have happened under an alternative. No treatment-effect conclusion should be drawn from the information recorded.

The safety counts indicate that adverse events were recorded among participants in the study arm, with serious and other events reported separately. They do not establish that the study regimen caused a particular event, and they do not replace the unreported Grade III/IV toxicity outcome. The listed percentages for selected serious-event terms are descriptive entries, not a comparative safety analysis.

Accordingly, what can be concluded is limited to the trial’s design, endpoint definition, enrollment description, and recorded safety counts. The registry does not report enough efficacy or analysis information to characterize the primary result, its precision, or a comparative effect. This is a limitation of the available registry record, not evidence for either a favorable or unfavorable clinical conclusion.

14. Why This Trial Matters Statistically

This trial illustrates a statistical distinction that matters in clinical research: defining an outcome is not the same as reporting its result. The registry gives a specific response rule based on radiologic imaging and RECIST, with an assessment time of 4 months. Yet it does not report the observed overall response rate. Without the estimate and its uncertainty, readers cannot judge either the outcome magnitude or its precision.

The single-group design also makes the target of inference important. A response percentage in one group would be a description of that group, not a randomized estimate of the difference between treatments. The record lists no control arm and no masking. Statistical interpretation must reflect those design features rather than imply a comparative conclusion.

The record also shows why analysis-population details matter. It reports withdrawals and participants considered not evaluable, but the available evaluability description is incomplete and endpoint handling is not stated. Such information is needed to understand the denominator behind an outcome rate and how incomplete assessments affect the estimate.

Finally, safety outcomes require careful distinctions. Counts of participants with serious or other adverse events do not automatically answer a separately listed question about Grade III/IV toxicities. Keeping endpoint definitions, analysis populations, and study design aligned helps prevent descriptive counts from being mistaken for a treatment comparison or a complete safety assessment.

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 for interpreting efficacy is that the registry record does not report the primary endpoint result. It provides no response percentage, response count, denominator, confidence interval, or test result. The number enrolled cannot be substituted for the endpoint analysis population, particularly because the record notes withdrawals and participants who were not evaluable.

The description of response evaluability is incomplete: its final criterion ends mid-sentence. The record does not state how the participants who withdrew consent or were not evaluable were handled, whether missing imaging occurred, or how any such missing assessments were analyzed. The complete analysis population is therefore not recoverable from the registry entry.

The single-group design has no concurrent control arm. It cannot provide a randomized contrast with another treatment, and the record does not report a statistical model or adjustment strategy. Allocation is listed as NA and masking as none. Details such as a protocol-level sample-size justification, interim analyses, and the planned statistical analysis are not reported in the registry record.

Although the record names Grade III/IV toxicities and progression-free survival as secondary outcomes, it does not report their results. The available serious and other adverse-event counts do not fill that gap. The serious-event terms are listed with percentages, but the record does not explain event overlap, timing, duration, or attribution. These limitations leave the endpoint descriptions and selected safety counts interpretable as registry information, while preventing a fuller assessment of efficacy, precision, and comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of a New Combination and Schedule of Chemotherapy Drugs for the Treatment of Head and Neck Cancer — NCT00148122.
• Registry record last updated 2014-04-17; status last verified 2014-03.
• Results first posted 2014-03-28.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed Phase II, single-group trial sponsored by University of Michigan Rogel Cancer Center. It enrolled 40 patients with metastatic or advanced, locally recurrent head and neck cancer to receive docetaxel and capecitabine. The study began in 2002-11 and had primary completion in 2008-08.

The primary endpoint was overall response rate at 4 months, defined using radiologic imaging and RECIST. The registry also lists Grade III/IV toxicities and progression-free survival as secondary outcomes. It reports no analysis entries and does not report the primary response result or results for those secondary outcomes.

For safety, the record lists 25 participants with serious adverse events among 38 at risk and 36 with other adverse events among 38 at risk, with selected serious-event terms and percentages. The response population description notes 2 consent withdrawals and 2 participants not evaluable, but the available evaluability text is incomplete.