Pazopanib Hydrochloride in Treating Patients With Stage IV or Recurrent Nasopharyngeal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pazopanib Hydrochloride in Treating Patients With Stage IV or Recurrent Nasopharyngeal Cancer (NCT00454142), a na phase 2 study. The primary outcome is Clinical Benefit Rate.

2. Clinical Question

3. Trial Design

This was a phase 2, single-group, unmasked study sponsored by the National Cancer Institute. The registry lists 33 participants as enrolled and the study status as completed. The record gives a start of 2007-08 and primary completion of 2010-04. It does not describe a randomized allocation or a control arm; allocation is listed as not applicable.

The treatment schedule specified oral pazopanib hydrochloride once daily on days 1-21, with courses repeating every 21 days if disease had not progressed and toxicity remained acceptable. The registry also lists a pharmacological study and computed tomography procedures. Pharmacological assessments were scheduled on day 1 and day 28, while CT was scheduled at baseline and day 28. The primary endpoint, clinical benefit rate, was assessed at 12 weeks using CT or MRI under RECIST version 1.0.

Other listed outcomes include response rate, progression-free survival, overall survival, toxicity, tumor blood flow, and pharmacokinetic measures. The record describes a planned toxicity outcome involving significant, grade 3/4 related adverse events. It also lists a day 28 trough-concentration measure using a threshold of 15 µg/mL and an AUC0-24h/dose measure on day 1. Numerical results for these efficacy and pharmacological outcomes are not reported in the registry record.

A single-group design can describe outcomes among participants who received the study treatment, but it does not provide a concurrent estimate of what would have happened under another treatment or control condition. Differences from other studies or historical groups cannot be attributed to the treatment on the basis of this design alone.

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: Once a subject signed the informed consent form, the required screening procedures would be performed.Eligible subjects would undergo 2 times of DCE-CT scan before study drug administration.

Overall Study

Reasons for not completing this period:

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 Clinical Benefit Rate, measured over 12 weeks of treatment.

The primary endpoint was clinical benefit rate at 12 weeks of treatment. It is a binary-response summary expressed as the percentage of participants who had at least one qualifying outcome: complete response, partial response, or stable disease. Under the registry’s RECIST version 1.0 definition, complete response means disappearance of all lesions; partial response means at least a 30% decrease in the sum of the longest diameters of target lesions; and stable disease means neither partial response nor progressive disease. CT or MRI was used for assessment.

General statistical context: a response-rate endpoint condenses each participant’s assessment into whether the specified benefit criterion was met. Reporting the percentage alongside the number assessed and a confidence interval helps readers judge both the observed frequency and its uncertainty. The endpoint can be useful in a single-group study because it describes the distribution of tumor-response categories at a specified assessment time. It does not, by itself, establish that the treatment caused those outcomes.

The registry names the endpoint and its 95% confidence interval as the dispersion measure, but the numerical rate, participant count contributing to it, and confidence limits are not reported in the registry record. Therefore, the observed endpoint cannot be quantified from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of endpoint is clinical benefit rate?

The primary endpoint is a binary participant-level outcome summarized as a percentage. Each participant’s tumor assessment is classified according to the response criteria, then counted as having clinical benefit if the classification is complete response, partial response, or stable disease. A participant whose classification falls outside those categories would not count toward the endpoint under the stated definition. This general explanation describes the logic of a binary rate; it does not establish how the registry handled participants without an assessment.

For a percentage to be interpretable, the numerator and denominator matter. The numerator is the count meeting the endpoint definition, and the denominator is the count included in the analysis. The registry record does not report either count for the primary endpoint. Although 33 participants were enrolled, enrollment alone does not establish how many had an evaluable assessment at 12 weeks or were included in the calculation.

What does a confidence interval communicate?

The registry identifies a 95% confidence interval as the dispersion measure for the primary endpoint. General statistical context: a confidence interval gives a range of values compatible with the observed data under the calculation method and its assumptions. It helps distinguish a relatively precise estimate from one with substantial uncertainty. It is not a guarantee that the true value lies in the interval, and it does not measure the probability that the treatment caused an outcome.

The endpoint’s numerical estimate and confidence limits are not reported in the registry record. The interval’s width, the degree of uncertainty, and whether the estimate is near any clinically relevant threshold therefore cannot be evaluated. No recalculated estimate is presented because the summary data needed to calculate one are absent.

How should the single-group design shape interpretation?

This is a single-group study, not a randomized comparison. General statistical context: observing an outcome after treatment describes what happened to the enrolled participants, but without a concurrent comparator it does not show what would have happened to comparable participants under another condition. Disease course, participant selection, other care, and assessment processes can all affect observed outcomes. The registry does not report a control group or a randomized allocation that could address those alternative explanations.

The study is also unmasked. The record does not describe masking of participants or investigators. General context: lack of masking can matter for outcomes involving judgment or decisions, although the size and direction of any effect cannot be determined from the design description alone. The stated use of CT or MRI and RECIST criteria specifies an assessment framework, but does not establish how assessors were organized or whether imaging was independently reviewed.

What do the planning illustrations represent?

Separate planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect set to a stated fraction of the observed effect. For time-to-event outcomes, the described planning quantity is a total number of events; for other outcomes it is participants per arm. These are hypothetical planning calculations, not results from the single-group trial and not observed power. Their two-arm assumptions should not be confused with the actual study design, which has one group.

General statistical context: a sample-size calculation asks what enrollment or event count might be needed under chosen assumptions to detect a specified effect with a chosen error rate and power. Such a calculation depends on the assumed effect and variability, among other inputs. It cannot establish what effect was actually observed, and it does not show that the completed study had a particular probability of detecting its effect. The registry does not report the trial’s own sample-size justification, so the planning illustrations should not be interpreted as the study’s original design rationale.

What can be inferred from the adverse-event summaries?

The record reports counts of participants affected in serious and other adverse-event categories and provides percentages for selected serious-event terms. These summaries are descriptive. General statistical context: counts and percentages describe reported events in the recorded group; they do not, without a comparison group and additional detail, quantify excess risk caused by treatment. An event’s seriousness, its grade, and its relationship to treatment are distinct classifications. The listed serious-event terms should not be assumed to be identical to the separate toxicity outcome defined as significant, grade 3/4 related adverse events.

The record does not provide timing, exposure duration, participant-level overlap across event terms, or detailed attribution for the listed terms. Consequently, the percentages should be read as registry summaries rather than as complete event histories. The stated number at risk is useful context, but it does not resolve the missing details for individual terms.

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("Treatment (Tyrosine Kinase Inhibitor)")
n      <- c(33)
events <- c(18)
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  Treatment (Tyrosine Kinase Inhibitor)  33  18  54.5  36.4  71.9  38.0  70.2  37.9  70.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes, including the primary clinical benefit rate and secondary response, survival, safety, blood-flow, and pharmacokinetic measures. When several outcomes are examined, general statistical context is that the chance of at least one nominally unusual result can increase if each is tested separately. A statistical plan may address this through a prespecified hierarchy or adjustment, but such an approach cannot be assumed. The registry record does not report a multiplicity-adjustment strategy or a hierarchy governing interpretation of the listed outcomes.

The record identifies a primary endpoint and names a 95% confidence interval as its dispersion measure. It does not report the numerical primary result or interval, and it does not describe a broader statistical analysis plan. Interim analyses, stopping rules, and any adjustment related to repeated looks at accumulating data are not reported in the registry record. Their absence from the record should not be taken as proof that none occurred.

The registry gives enrollment as 33 but does not state the analysis population for the primary endpoint or the number with evaluable 12-week assessments. A missing-data method, rules for handling participants who discontinued treatment, and methods for incomplete imaging assessments are not reported in the registry record. Without these details, readers cannot determine whether the endpoint denominator included every enrolled participant, only assessed participants, or another defined group.

Likewise, analysis populations for the secondary outcomes and handling of missing survival, safety, or pharmacological measurements are not reported in the registry record. The count of enrolled participants should not be treated as the denominator for every outcome. These gaps limit reproducibility and make it difficult to assess whether outcome-specific exclusions or missing observations could influence the reported summaries.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hemorrhage (9.1%), infection (6.1%), pericardial effusion (3.0%), hyperbilirubin (3.0%), pain (3.0%).

The registry lists 33 participants at risk in the treatment group. It records 10 affected participants in the serious-event category and 11 in the other-event category. The serious-event terms listed with percentages are hemorrhage at 9.1%, infection at 6.1%, pericardial effusion at 3.0%, hyperbilirubin at 3.0%, pain at 3.0%, and myocardial infarction at 3.0%. The record does not provide a separate denominator for each term, so these percentages should be read as the registry presents them rather than reverse-engineered into counts.

General statistical context: “serious” describes an event classification, while grade describes severity and relatedness describes an attribution to treatment. They are not interchangeable. The listed serious-event terms are not necessarily the same measure as the separate secondary outcome for significant grade 3/4 related adverse events. The adverse-event summaries do not establish that treatment caused an event, and the single-group design offers no concurrent comparison for estimating relative risk. Timing, duration, recurrence, and participant-level overlap among terms are not reported in the registry record.

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

The registry record establishes that a completed, single-group phase 2 study enrolled 33 participants with recurrent or stage IV nasopharyngeal carcinoma and specified pazopanib hydrochloride as the treatment. It also defines a primary clinical benefit endpoint at 12 weeks and describes how response categories were to be assessed. These registry entries characterize the research question and design, but they do not provide the primary endpoint result.

The numerical clinical benefit rate and its 95% confidence interval are not reported in the registry record. As a result, readers cannot tell from the record how many participants met the endpoint, how uncertain the percentage was, or how the outcome was distributed among complete response, partial response, and stable disease. The enrollment count cannot fill in these missing result details.

The adverse-event summaries give counts of affected participants and percentages for selected serious-event terms. They are descriptive observations in a single treatment group. They do not establish that pazopanib caused the listed events, quantify a comparison against another treatment, or describe the entire safety profile. The trial’s listed secondary survival and pharmacological outcomes also cannot be interpreted numerically because their results are not reported in the registry record.

General statistical context: a single-group study can provide information about observed outcomes under its study conditions. A causal comparison requires a suitable comparator and an analysis that addresses the design and relevant sources of bias. Neither an endpoint label nor completion status is evidence that a treatment is effective or ineffective. The registry record supports a careful account of the trial’s methods and limited posted safety summaries, but not a conclusion about comparative benefit or harm.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how a phase 2, single-group trial frames a clinical question around a defined response endpoint. The clinical benefit rate combines complete response, partial response, and stable disease at a specified assessment time. Understanding that definition is essential: a rate is meaningful only in relation to its response rules, assessment schedule, analysis denominator, and uncertainty.

The design also illustrates the boundary between describing outcomes and making comparative claims. A single treatment group can document what was observed among enrolled participants, but it cannot supply a concurrent counterfactual comparison. This distinction remains important even when outcomes are defined using standardized imaging criteria. A clear endpoint definition improves interpretability; it does not remove the limitations of an uncontrolled design.

The record further illustrates why outcome availability matters alongside outcome selection. It lists several secondary domains, including survival, toxicity, blood flow, and pharmacokinetics, yet their numerical results are not reported in the registry record. For the primary endpoint, even though its confidence-interval measure is named, the estimate and limits are absent. A registered endpoint without a numerical result cannot answer how large or precise the observed outcome was.

Finally, the safety entries demonstrate the need to distinguish event counts, term-specific percentages, seriousness, grade, and relatedness. Those categories answer different questions. Keeping them separate prevents descriptive event summaries from being mistaken for a comparative estimate of treatment-attributable risk. This trial therefore offers a useful setting for reading endpoint definitions and design limitations together, while its missing outcome details constrain statistical conclusions.

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 principal limitation for statistical interpretation is that the registry record does not report the numerical primary clinical benefit rate or its confidence interval. It also does not report the number of participants included in that calculation or the response-category counts. The 33 enrolled participants cannot be assumed to equal the primary endpoint analysis population.

The single-group design has no concurrent control arm, and allocation is listed as not applicable. This prevents a direct within-trial comparison with another treatment or control condition. The study is unmasked, and the record does not describe independent imaging review or assessor masking. These design features do not establish that bias occurred, but they limit what can be ruled out from the registry description.

Additional eligibility criteria, baseline participant characteristics, treatment exposure, discontinuations, and the handling of missing assessments are not reported in the registry record. The record does not explain how incomplete CT or MRI assessments or participants who stopped treatment were treated in the primary analysis. Numerical findings for most listed secondary outcomes are also absent.

For safety, the registry lists affected-participant counts and selected serious-event terms, but does not give term-specific denominators or details such as timing, duration, recurrence, overlap, and attribution. Those omissions limit interpretation of the event percentages and prevent a complete account of the safety experience. The study’s own sample-size justification, interim-analysis approach, and detailed statistical plan are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pazopanib Hydrochloride in Treating Patients With Stage IV or Recurrent Nasopharyngeal Cancer — NCT00454142.
• Registry record last updated 2015-12-17; status last verified 2012-01.
• Results first posted 2015-12-17.
• 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 completed phase 2 study examined pazopanib hydrochloride in a single group of Asian patients with recurrent or stage IV nasopharyngeal carcinoma. Enrollment was 33. Treatment was oral pazopanib once daily on days 1-21, with courses repeating every 21 days if disease had not progressed and toxicity remained acceptable.

The primary endpoint was clinical benefit rate at 12 weeks, defined by RECIST version 1.0 as complete response, partial response, or stable disease, assessed using CT or MRI. The numerical primary result, confidence interval, and analysis denominator are not reported in the registry record. The record lists 10 participants affected in the serious-event category and 11 in the other-event category, along with selected serious-event terms and percentages. The single-group design does not support a direct treatment comparison.