Trial of RAD001 and Erlotinib With Recurrent Head and Neck Squamous Cell Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of RAD001 and Erlotinib With Recurrent Head and Neck Squamous Cell Carcinoma (NCT00942734), a na phase 2 study. The primary outcome is 12-Week Progression-Free Survival (PFS).

2. Clinical Question

This question is narrower than asking whether the combination improves outcomes compared with another treatment. Without a concurrent control group, the trial can describe outcomes among participants receiving the combination, but it cannot by itself separate a treatment effect from the course of the disease, participant selection, or other influences. The record identifies the study as phase II and lists M.D. Anderson Cancer Center as sponsor. It began in 2009-07, reached primary completion in 2014-11, and is marked completed. Those record details establish the study context, but they do not supply the missing primary outcome result or explain the reasons that eight participants were not evaluable.

3. Trial Design

This was a phase II, single-group clinical trial of RAD001 plus erlotinib for recurrent squamous cell carcinoma of the head and neck. The registry lists 49 participants as enrolled. Allocation is recorded as not applicable, and masking is recorded as none. There is no randomized comparator arm described, so the design is not a controlled comparison of the combination against another treatment or against usual care.

Participants in the listed group received RAD001 5 mg by mouth every day and erlotinib 150 mg by mouth every day, during each 28 day study cycle. These are the regimen details in the registry record; additional treatment-delivery rules, such as dose changes, treatment interruptions, or adherence assessment, are not reported in the registry record. The stated aims were to learn whether the combination could help control the cancer and to study its safety.

The primary outcome was 12-week progression-free survival, reported as a percentage of participants. The registry describes imaging assessments by CT or MRI after 4 weeks, after 12 weeks, and every 8 weeks thereafter. It records primary completion in 2014-11 and overall study status as completed. Eight participants were not evaluable for the primary outcome, but the record does not give reasons or identify how those participants were handled in the primary analysis.

A single-group phase II design can provide descriptive information about outcomes and adverse events in the participants treated. It does not supply a concurrent estimate of what would have happened to comparable participants without the study combination. Therefore, even a reported outcome percentage would need to be interpreted as an observed result in this group, not as a direct estimate of benefit relative to a control. The registry record does not report the protocol's sample-size justification, a detailed statistical analysis plan, or an explanation of the design choices.

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: Of the forty-nine participants registered, six participants were ineligible and not treated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Eight participants were not evaluable.

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 12-Week Progression-Free Survival (PFS), measured over 12 weeks.

The primary endpoint is titled 12-Week Progression-Free Survival (PFS) and is expressed as a percentage of participants. The registry defines progression-free survival for this outcome as stable disease or better at the assessment point. Tumor status was to be assessed by CT or MRI after 4 weeks, after 12 weeks, and then every 8 weeks thereafter. Participants who received at least one dose of RAD001 plus erlotinib and died before 12 weeks were counted as having progressive disease.

The registry describes response using RECIST criteria. Complete response means disappearance of all target lesions. Partial response requires a >30% decrease in the sum of the longest diameters of target lesions, using the baseline sum as the reference. Progressive disease is a >20% increase from the smallest recorded sum since treatment started, or the appearance of one or more new lesions. Stable disease is neither enough shrinkage to qualify as a partial response nor enough increase to qualify as progression, using the smallest sum since treatment started as the reference.

As a general statistical concept, a fixed-time percentage can summarize how many participants meet a defined disease-status criterion at a particular assessment. It is not the same presentation as a full time-to-event analysis, which uses the timing of events and usually describes how follow-up and censoring were handled. The registry labels this endpoint PFS but presents it as a percentage at 12 weeks. The record does not report the observed percentage, its numerator or denominator, or an uncertainty interval. Eight participants were not evaluable, and the record does not explain their reasons or how they were accounted for in the reported outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a fixed-time percentage describe?

As a general statistical concept, a percentage at a specified assessment summarizes the proportion of an analysis population that meets a defined condition at that time. Here, the condition is the registry's definition of stable disease or better at 12 weeks. Such a measure depends on the precise outcome definition and on which participants are included in the denominator. The registry supplies the endpoint definition and notes that eight participants were not evaluable, but it does not report the analyzed denominator or the numerical percentage.

A fixed-time percentage is distinct from a complete time-to-event analysis. A time-to-event approach uses when each event occurs and needs rules for handling participants whose event status is not observed during follow-up. A percentage at one assessment compresses follow-up into status at that particular time. The registry's title uses the term progression-free survival, while its unit is percentage of participants and its definition is stable disease or better at the 12-week assessment. The record does not provide a time-to-event curve, an event-time estimate, or details about censoring.

How do the imaging criteria define disease status?

The endpoint relies on tumor assessments by CT or MRI. The stated schedule includes assessment after 4 weeks, after 12 weeks, and every 8 weeks thereafter. The registry uses RECIST definitions: complete response is disappearance of all target lesions; partial response requires a >30% decrease in the sum of longest diameters from baseline; and progressive disease is a >20% increase from the smallest recorded sum since treatment started or the appearance of one or more new lesions. Stable disease falls between the partial-response and progressive-disease thresholds, using the smallest sum since treatment started as the reference. These rules translate imaging observations into categories, but the record does not report who assessed scans, whether assessments were independently reviewed, or how disagreements were resolved.

The death rule is also part of the endpoint definition: participants who received at least one dose and died before 12 weeks were counted as having progressive disease. That makes death before the assessment a failure to meet the progression-free endpoint under the stated rule. The registry does not report how other missing scans, treatment discontinuations, or unevaluable assessments were handled.

What can a single-group design estimate?

As a general statistical concept, a single-group study can estimate the observed outcome frequency among participants treated under the study conditions. It cannot directly estimate a between-treatment contrast because no concurrent control group is described. Any comparison with an external benchmark would require relevant information about that benchmark and assumptions about comparability; the registry record does not report such a comparison. The design is listed as single group, with allocation not applicable and masking none. These are essential context for understanding what an outcome estimate would and would not represent.

How should uncertainty be read?

As a general statistical concept, a confidence interval describes a range of values compatible with the observed data under a specified statistical method. It helps show the precision of an estimate: a wider interval indicates greater uncertainty, while a narrower interval indicates greater precision. The registry record does not report a confidence interval for the primary outcome, so its statistical precision cannot be evaluated. It also does not report a p value, a hypothesis test, or an inferential model for the primary outcome.

For a percentage endpoint, the estimate and its uncertainty depend on the number of participants counted as meeting the endpoint and the analysis denominator. Those counts are not reported for the primary outcome. The enrollment count of 49 and the note that eight participants were not evaluable do not by themselves establish the analyzed denominator or outcome frequency. They must not be used to reconstruct a result without the relevant analysis details.

What is not specified about the analysis?

The registry record does not report a detailed statistical analysis plan, the intended analysis population, a sample-size justification, or interim-analysis procedures. It does not state whether the primary outcome was intended to be analyzed with a particular model or whether any adjustment for prognostic factors was planned. No analysis entries are listed. These omissions mean that the statistical framework for interpreting the endpoint cannot be reconstructed from the record.

The record includes planning illustrations based on an observed effect as a separate statistical exercise. Such illustrations are assumptions-based planning quantities, not observed trial outcomes and not evidence of observed power. The registry record does not provide the primary outcome estimate needed to judge an effect size in this explanatory text. More generally, a planning calculation does not replace a reported outcome, confidence interval, or analysis description.

Because the primary endpoint result and its analysis details are absent, the most defensible statistical reading is descriptive: the registry states what was intended to be measured and how disease categories were defined, but it does not post the numerical result needed to quantify the endpoint or its uncertainty.

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("RAD001 + Erlotinib")
n      <- c(35)
events <- c(17)
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  RAD001 + Erlotinib  35  17  48.6  31.4  66.0  33.0  64.4  32.9  64.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, 12-week progression-free survival, and no analysis entries. It does not report whether additional outcomes were tested, whether there was a hierarchy of outcomes, or whether any adjustment for multiple comparisons was planned. Multiplicity refers, in general, to the increased chance of a false-positive finding when multiple statistical hypotheses are tested. Whether that issue affected this trial's analyses cannot be determined from the registry record.

Missingness is particularly relevant because the record says that eight participants were not evaluable for the primary outcome. It does not report why they were not evaluable, when their assessments became unavailable, or whether missingness was related to disease status, treatment exposure, or another factor. It also does not state whether the main analysis included all enrolled participants, only participants who received treatment, or another analysis population. The endpoint description specifies that participants who received at least one dose and died before 12 weeks were counted as having progressive disease, but that rule does not explain the handling of other missing outcome assessments.

As a general statistical concept, different approaches to missing outcome data can lead to different estimates, especially when the reason for missingness is associated with the outcome. Sensitivity analyses can explore how conclusions change under alternative assumptions, but the registry record does not report such analyses. It likewise does not report an imputation method or a complete-case rule.

The absence of the numerical primary result, denominator, analysis population, and missing-data method limits assessment of both the estimate and its potential bias. The enrollment count and the unevaluable-participant count do not suffice to reconstruct those details.

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: hypercalcaemia (2.3%).

The registry reports safety counts for the RAD001-plus-erlotinib group. For serious adverse events, 43 participants are listed as at risk and 1 as affected. Hypercalcaemia is listed among the top serious terms at 2.3%. The record does not report a death count in these adverse-event figures. A missing death value should not be interpreted as evidence that no deaths occurred.

For other adverse events, the registry lists 43 participants at risk and 43 affected. This is a count of participants reported as affected in that category, not a description of how many distinct events occurred or how severe they were. The registry's categories should be kept separate: the other-adverse-event count is not a substitute for the serious-adverse-event count.

As a general statistical concept, adverse-event summaries depend on definitions, follow-up duration, collection procedures, and the population included. The record does not provide detailed event-level descriptions, exposure-adjusted rates, or causal assessments for the counts. The single-group design also does not provide a concurrent treatment group for comparing safety frequencies. These figures describe the posted registry entries and do not, by themselves, establish that an event was caused by either study drug.

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

The registry record establishes that a phase II, single-group study evaluated daily RAD001 and erlotinib in recurrent squamous cell carcinoma of the head and neck. It also gives a specific primary endpoint: the percentage of participants with stable disease or better at 12 weeks, using stated imaging and RECIST criteria. These details make the intended clinical question understandable.

However, the registry does not post a numerical primary outcome result. It gives no outcome percentage, count meeting the endpoint, confidence interval, or test result. Therefore, the record cannot show how frequently participants met the endpoint or how precisely that frequency was estimated. The count of 49 enrolled and the note that eight were not evaluable do not replace the missing primary result or clarify the analysis denominator.

The design also limits the kind of conclusion that could be drawn even if the outcome estimate were available. A single-group study can describe what occurred among participants receiving the combination, but there is no concurrent control group for estimating a comparative effect. The data cannot, on their own, distinguish the contribution of treatment from other explanations for observed outcomes. The absence of masking is another design feature to consider when interpreting assessments, although the record does not report how outcome assessments were conducted.

The adverse-event entries offer limited descriptive safety information: 1 of 43 participants at risk is listed as affected for serious adverse events, hypercalcaemia is reported at 2.3% among the top serious terms, and 43 of 43 are listed as affected for other adverse events. The record does not report a death count in those figures or provide enough detail to characterize event timing, duration, or causality.

In short, the registry describes the intervention, study structure, outcome definition, and selected safety counts, but it does not provide the primary efficacy result or a comparative estimate. The posted information is insufficient to quantify the primary outcome or determine its statistical precision.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why a clearly defined endpoint and a reported estimate are both necessary. The registry gives operational rules for classifying tumor response and progression, including imaging modalities, assessment timing, and RECIST thresholds. Those details clarify what the investigators intended to count as disease control at 12 weeks. Yet without the observed endpoint count and denominator, readers cannot calculate or assess the reported frequency from the registry record.

The design also illustrates the distinction between describing an outcome and estimating a comparative treatment effect. In a single-group study, an observed proportion can characterize participants treated in that study, but there is no randomized control group to anchor a direct comparison. This matters especially when the clinical question uses language about whether a combination can help control disease: the outcome definition alone does not establish a treatment effect.

The record's note that eight participants were not evaluable highlights the importance of documenting analysis populations and missing-data handling. A reader needs to know which participants contribute to the endpoint, why assessments are missing, and how those cases were treated. Without those details, the endpoint's denominator and potential sensitivity to missingness remain unclear.

The safety entries likewise show why event counts require context. Serious and other adverse events are listed separately, while the record does not provide event-level detail or a death count. A count can be useful as a descriptive signal, but its interpretation depends on definitions, follow-up, and ascertainment. The registry makes some study features visible while leaving key results and methods unavailable, demonstrating how registration details and posted outcome data serve different purposes.

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 most important limitation for statistical interpretation is that the registry record does not report a numerical result for the primary endpoint. There is no posted percentage, numerator, denominator, confidence interval, or statistical test result for 12-week progression-free survival. As a result, neither the outcome magnitude nor its precision can be assessed.

The single-group design has no concurrent control arm, so it does not support a direct between-group treatment-effect estimate. Allocation is listed as not applicable and masking as none. The record does not describe blinded outcome review or independent radiology assessment. It therefore does not establish how much protection there was against assessment-related influences.

Eight participants were not evaluable for the primary outcome, but reasons, timing, and handling are not reported. The record does not identify the primary analysis population or give the denominator used for the endpoint. Although it specifies how deaths before 12 weeks were classified for participants who received at least one dose, the handling of other missing assessments is not stated.

The registry record does not report a detailed statistical analysis plan, sample-size justification, interim-analysis procedures, or methods for multiplicity. It also does not report a primary endpoint analysis entry. These omissions prevent assessment of whether the posted outcome, had it been reported, followed a prespecified method.

Safety interpretation is limited by the aggregate nature of the counts. The record gives serious and other adverse-event counts and a serious-term frequency, but does not provide event-level timing, duration, severity detail, exposure-adjusted rates, or a death count. It does not establish causal attribution. These trial-specific reporting gaps limit the conclusions that can be drawn from the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Trial of RAD001 and Erlotinib With Recurrent Head and Neck Squamous Cell Carcinoma — NCT00942734.
• Registry record last updated 2026-07-07; status last verified 2026-06.
• Results first posted 2016-02-04.
• 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 NCT00942734, a completed phase II, single-group study sponsored by M.D. Anderson Cancer Center. It enrolled 49 participants with recurrent head and neck squamous cell carcinoma and evaluated RAD001 5 mg by mouth daily plus erlotinib 150 mg by mouth daily during each 28 day cycle. The record lists no masking and no comparator group.

The primary outcome was 12-week progression-free survival, expressed as a percentage of participants and defined as stable disease or better under the stated RECIST criteria. Eight participants were not evaluable. The registry does not report the numerical primary outcome, its denominator, or an uncertainty estimate. It lists 43 participants at risk and 1 affected for serious adverse events, hypercalcaemia at 2.3% among the top serious terms, and 43 at risk and 43 affected for other adverse events. A death count is not reported in the adverse-event figures.