Phase II Trial Evaluating Axitinib In Patients With Unresectable, Recurrent Or Metastatic Head And Neck Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Trial Evaluating Axitinib In Patients With Unresectable, Recurrent Or Metastatic Head And Neck Cancer (NCT01469546), a na phase 2 study. The primary outcome is Percentage of Patients Alive and Free of Progression at 6 Months.

2. Clinical Question

3. Trial Design

This was a phase II, prospective, single-institution, single-arm study of axitinib in patients with unresectable, recurrent or metastatic head and neck squamous cell carcinoma. The intervention is listed as axitinib (AG-013736). The study summary describes the drug as a pill taken twice a day. Masking was absent, and the study was open-label. Allocation is listed as not applicable because there was no randomized assignment among treatment groups.

The arm description states that eligible patients had received no more than two prior lines of systemic therapy for recurrent or metastatic head and neck cancer. The registry record lists 42 enrolled patients. For the primary endpoint, it says 12 patients did not complete the first cycle or undergo repeat tumor imaging because of an adverse event, disease progression, non-compliance or physician discretion. It states that 30 patients were analyzed.

The primary endpoint was the percentage of patients alive and free of progression at 6 months. Secondary outcomes listed in the record include response or stable disease, grade 3 or 4 toxicities, and median progression-free survival. The registry record does not report results for those outcomes in the information. It also does not report a statistical analysis plan, a sample-size justification, or details of interim analyses. The study status is completed, but completion status alone does not supply endpoint results or establish how the study findings should be interpreted.

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: 42 patients were enrolled. 12 patients did not complete the first cycle or undergo repeat tumor imaging (due to adverse event, disease progression, non-compliance or physician discretion). Only 30 patients were analyzed..

Received 5 mg Dose

Reasons for not completing this period:

Dose Escalation to 10 mg

Analysis population for the primary outcome, as defined in the registry: 42 patients were enrolled. 12 patients did not complete the first cycle or undergo repeat tumor imaging (due to adverse event, disease progression, non-compliance or physician discretion). Only 30 patients were analyzed.

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: 42 patients were enrolled. 12 patients did not complete the first cycle or undergo repeat tumor imaging (due to adverse event, disease progression, non-compliance or physician discretion). Only 30 patients were analyzed.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patients Alive and Free of Progression at 6 Months, measured over 6 months.

The primary endpoint is the percentage of patients alive and free of progression at 6 months. Progression-free survival combines two events relevant to the endpoint: disease progression and death. At the stated time point, the measure describes the proportion meeting the endpoint definition, rather than the duration of disease control for each individual or a comparison between treatments.

As a general statistical explanation, a fixed-time progression-free survival rate can give a clinically interpretable snapshot of the trial population's status at a specified follow-up point. Its interpretation depends on how progression and death were defined, how follow-up was handled, and which patients contributed to the analysis. Those details are not reported in the registry record. The record names the endpoint and its timeframe, but does not provide the observed rate, an uncertainty interval, or further information on censoring and assessment procedures. Consequently, the estimate's magnitude and precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-arm design estimate?

This study is described as single-arm, with no concurrent control group. In general, a single-arm trial estimates outcomes among the participants who receive the intervention under the study conditions. It does not directly estimate the contrast between that intervention and a comparison treatment. Historical results may sometimes be used for context, but no such comparison or benchmark is reported in the registry record. Differences between a study group and a separate population can reflect differences in eligibility, disease status, follow-up or other factors, as well as treatment.

The trial was open-label and masking was listed as absent. As a general matter, lack of masking may matter when outcomes depend on clinical assessment or participant reporting. The record does not report whether progression assessments were independently reviewed or what procedures were used to reduce assessment bias.

How should a fixed-time rate be understood?

The primary outcome is a percentage of patients alive and free of progression at 6 months. In general, a fixed-time rate expresses the share of an analysis population meeting a specified status at a particular follow-up point. It is distinct from a median time-to-event measure: the two summarize different aspects of outcomes and are not interchangeable. The registry record provides the endpoint definition and timeframe but not the observed rate, uncertainty interval, or calculation details.

As a general statistical concept, a confidence interval describes a range of estimates compatible with the data under the method's assumptions, and communicates uncertainty around an estimate. The registry record does not report a confidence interval for the primary endpoint. It also does not report the statistical method used to obtain the rate or its uncertainty, so no particular interval method can be attributed to this trial.

Why does the analysis population matter?

The record says 42 patients were enrolled and 30 were analyzed for the primary endpoint. It also reports that 12 did not complete the first cycle or undergo repeat tumor imaging, with reasons including adverse event, disease progression, non-compliance or physician discretion. In general, excluding participants from an endpoint analysis can affect the estimate if the excluded participants differ in outcome from those retained. This is especially relevant when reasons for exclusion may relate to disease status or treatment experience.

The record does not describe the endpoint handling of those 12 patients, whether follow-up information was used for any of them, or whether additional missing endpoint data occurred among the analyzed group. It does not state whether the analysis was based on all enrolled participants, a prespecified subset, or another analysis population definition. These points are not reported in the registry record, so the potential influence of missing outcome information cannot be quantified.

What can the safety summaries tell readers?

The record reports 42 patients at risk for the serious adverse-event summary and 22 affected by a serious adverse event. It also lists 42 at risk and 37 affected for other adverse events. These are different summaries and should not be combined. The serious-event terms include death not associated with a CTCAE term and several other categories. The registry record does not give a patient-level breakdown, explain whether categories overlap, or state the causal relationship between events and treatment. As a general principle, adverse-event listings describe events observed and recorded during a study; they do not, alone, establish causation.

Over-dispersion is a general statistical issue in count data when observed variability exceeds what a simple model assumes. It can affect uncertainty estimates and model fit. The record does not identify a count model or report an over-dispersion analysis; therefore, this concept should not be mistaken for a method used in this trial.

What statistical plan is documented?

The registry record does not report a statistical analysis plan, the method for the primary endpoint, a sample-size justification, or interim analyses. It lists secondary outcomes but does not provide the corresponding results or describe how multiple outcomes were handled. General methods such as adjustment for multiple comparisons, sensitivity analyses or prespecified subgroup analyses cannot be attributed to this study without documentation. The absence of these details limits the ability to assess whether analyses were planned in advance and how robust the reported findings would be. No primary endpoint estimate is reported in the registry record, so recalculation from posted summary statistics is not possible.

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("Axitinib (AG-013736)")
n      <- c(30)
events <- c(8)
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  Axitinib (AG-013736)  30  8  26.7  12.3  45.9  14.2  44.4  14.2  44.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and secondary outcomes, including response or stable disease, grade 3 or 4 toxicities, and median progression-free survival. It does not report a statistical analysis plan or explain whether and how the interpretation of multiple outcomes was addressed. Any multiplicity procedure, hierarchy among outcomes, or distinction between confirmatory and exploratory analyses is not reported in the registry record.

For the primary endpoint, the record states that 42 patients were enrolled, 12 did not complete the first cycle or undergo repeat tumor imaging, and 30 were analyzed. The reasons given include adverse event, disease progression, non-compliance or physician discretion. The record does not specify how those patients were handled in the endpoint calculation, whether the analysis population was defined before data review, or how any further missing information was treated. The impact of missing outcomes cannot be quantified from the available information.

The registry record does not report an approach to interim analyses, a sample-size justification, or details of sensitivity analyses. It also does not report the primary estimate or its uncertainty. These omissions mean readers cannot assess the planned error-control strategy, the influence of missing data, or the precision of the endpoint estimate based on the registry record. They do not establish that a particular analysis was or was not performed; those details are simply not reported in the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death not associated with ctcae term (14.3%), hemorrhage, gi (7.1%), hemorrhage, pulmonary/upper respiratory (4.8%), infection with unknown anc, lung (4.8%), pain, chest (4.8%).

The serious adverse-event summary lists 42 patients at risk and 22 affected. A separate summary lists 42 at risk and 37 affected for other adverse events. These figures describe different event groupings and should be read separately. The record also lists serious-event terms with percentages: death not associated with a CTCAE term, 14.3%; hemorrhage, GI, 7.1%; hemorrhage, pulmonary/upper respiratory, 4.8%; infection with unknown ANC, Lung, 4.8%; pain, Chest, 4.8%; and supraventricular and nodal arrhythmia, 2.4%.

These entries are event summaries, not evidence by themselves that axitinib caused an event. The registry record does not explain whether patients could appear in more than one category, provide event-level details, or report causal assessments. The listed term “Death not associated with CTCAE term” should be read as the label recorded for that serious adverse-event category, not as a complete accounting of deaths from any cause. These safety figures do not report the primary progression-free survival endpoint.

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

The study addresses a defined clinical research question: the six-month progression-free survival rate among patients with unresectable, recurrent or metastatic head and neck squamous cell carcinoma treated with axitinib. The registry record supplies design information and states that 30 patients were analyzed for the primary endpoint. However, it does not report the observed endpoint rate or its uncertainty. The outcome's magnitude and precision therefore cannot be interpreted from this record.

Even if an outcome estimate were available, this single-arm, open-label phase II design would describe the treated study group rather than provide a randomized treatment comparison. Without a concurrent comparator, differences from an external population would be difficult to attribute specifically to treatment. The registry record does not report a control group or an external benchmark.

The record's analysis population also warrants caution. It reports that 12 enrolled patients did not complete the first cycle or undergo repeat tumor imaging, for reasons that include adverse event and disease progression. The endpoint treatment of these patients is not reported in the registry record. The possible effect of their exclusion or missing follow-up therefore cannot be assessed.

The serious adverse-event figures provide a separate description of recorded safety events, but do not establish causation or replace the efficacy endpoint. Details about overlap among event categories and causal assessments are not reported. The record also does not report the statistical analysis plan, sample-size justification, interim analyses or multiplicity approach. These limitations mean the registry record supports a description of the trial design and selected recorded outcomes, but not a conclusion about the size, precision or comparative meaning of the primary result.

14. Why This Trial Matters Statistically

This trial illustrates why design and analysis populations are central to interpreting a phase II study. A single-arm study can describe outcomes in a treated group, but has no randomized concurrent comparator to separate treatment effects from other explanations. The open-label design adds a related consideration for outcomes that involve clinical assessment. Neither feature makes the endpoint meaningless; both shape what conclusions the design can support.

The primary endpoint is a fixed-time progression-free survival rate, and the record identifies the analysis population as 30 patients. It also notes that 12 enrolled patients did not complete the first cycle or undergo repeat imaging, including because of adverse event or progression. How those patients were handled is not reported in the registry record. This makes the distinction between enrollment and endpoint analysis especially important when interpreting any estimate.

The registry record does not report the primary estimate or its uncertainty. That absence prevents readers from assessing the endpoint's magnitude and precision. It also does not report key analytical details, including the statistical plan and handling of multiple outcomes. The listed serious adverse-event summaries offer some safety information, but they do not resolve these gaps or establish causality.

Statistically, the study is useful as an example of the limits of interpreting a named endpoint without its result and analysis details. It shows why readers need the endpoint estimate, uncertainty, analysis-population definition, and transparent handling of missing outcomes to evaluate what the evidence can support. The record documents a focused research question and a completed phase II design, while leaving those interpretive elements not reported in the registry record.

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 registry record does not report the primary endpoint result, so its magnitude and precision cannot be evaluated. It also does not report a confidence interval or the statistical method used to calculate the six-month rate. The listed analysis population is 30 patients, while 12 enrolled patients did not complete the first cycle or undergo repeat tumor imaging. Their endpoint handling is not reported in the registry record; the listed reasons include adverse event, disease progression, non-compliance or physician discretion.

The study was single-arm and open-label, with no concurrent comparator. This limits treatment-effect comparisons and leaves the potential influence of assessment expectations unclear. Procedures for progression assessment, including any independent review, are not reported in the registry record. The record also does not state whether endpoint definitions or analysis populations were prespecified.

Other missing information includes the statistical analysis plan, sample-size justification, interim-analysis procedures, multiplicity handling, and sensitivity analyses. Although secondary outcomes are listed, their results are not reported in the registry record. The serious adverse-event summaries do not include causal assessments or clarify whether event categories overlap. These limitations are specific to what the record documents and prevent a fuller assessment of efficacy, uncertainty, missing-data effects and safety attribution.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Trial Evaluating Axitinib In Patients With Unresectable, Recurrent Or Metastatic Head And Neck Cancer — NCT01469546.
• Registry record last updated 2016-08-29; status last verified 2016-07.
• Results first posted 2015-12-09.
• 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, open-label, single-arm phase II study of axitinib in unresectable, recurrent or metastatic head and neck squamous cell carcinoma. The primary endpoint was the percentage of patients alive and free of progression at 6 months. The record states that 42 patients were enrolled, 12 did not complete the first cycle or undergo repeat tumor imaging, and 30 were analyzed. It lists serious adverse-event summaries and secondary outcomes. The primary endpoint result, its uncertainty, and key statistical-analysis details are not reported in the registry record. With no concurrent comparator, the design describes outcomes in the treated group rather than a randomized treatment contrast.