Neoadjuvant Axitinib in Locally Advanced Renal Cell Carcinoma (RCC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neoadjuvant Axitinib in Locally Advanced Renal Cell Carcinoma (RCC) (NCT01263769), a na phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

The study asks whether axitinib given before surgery is associated with an objective response in people with locally advanced clear cell renal cell carcinoma. The registry describes a Phase II trial with one treatment group and an objective response assessment after 12 weeks. It also states that safety was to be studied.

The response definition combines complete response, described as disappearance of the renal mass, and partial response, defined by a decrease of 30% or greater in the largest diameter relative to baseline. The registry record does not report the number of participants who met either response category or an overall response estimate. It therefore states the question and its measurement approach, but does not provide the primary outcome result needed to answer it. Without a control group, even a reported response proportion would describe outcomes in the treated group rather than establish how those outcomes compare with another treatment or with no treatment.

3. Trial Design

This is a Phase II, single-group trial of neoadjuvant axitinib in locally advanced clear cell renal cell carcinoma. The record lists the study as completed and reports enrollment of 39. The start date is 2011-02 and the primary completion date is 2021-02. These registry entries describe the study record; they do not establish when each participant entered or completed treatment.

The intervention is axitinib, a drug. The arm description gives a starting dose of 5 mg by mouth twice each day for 12 weeks. The primary outcome is assessed at 12 weeks, when CT abdomen is done. The stated response categories are complete response and partial response according to RECIST v1.0. The registry record does not give details about treatment modifications, adherence, surgery timing, or how participants who did not complete the planned treatment were handled.

The study is not randomized: allocation is listed as not applicable, masking is listed as none, and the model is single group. There is therefore no concurrent control arm in the registry design. The intervention group cannot be compared with a separate group assigned to another treatment or to no intervention. The registry record does not report a protocol-level sample-size justification, a planned interim analysis, or a detailed statistical analysis plan.

Secondary outcomes listed are recurrence-free survival, overall survival, postoperative complications of any grade, and high-grade surgery-related complications. The record lists five outcome measures but reports zero analyses. It gives no outcome estimates or analysis results for the primary or secondary measures. The enrollment figure is not the same as a confirmed count in the primary endpoint analysis; the record does not report how many participants contributed evaluable imaging or were included in an endpoint analysis.

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: 39 participants consented, but 14 not treated (11 not meeting criteria and 3 declined). Only 25 underwent treatment

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 Objective Response Rate, measured over 12 weeks.

The primary endpoint is objective response rate, expressed as the percentage of participants with an event. The event is a complete or partial response assessed with CT abdomen after 12 weeks of treatment. Under the stated RECIST v1.0 definition, complete response means complete disappearance of the renal mass. Partial response means a decrease of 30% or greater in its largest diameter, using the baseline largest diameter as the reference.

A response endpoint offers a defined way to describe tumor change over a specified assessment period. Combining complete and partial responses produces a proportion that can be interpreted as the share of assessed participants meeting either response criterion. In general, a prespecified response definition helps make outcome classification more consistent than an informal judgment of improvement. The endpoint does not, by itself, describe how long a response lasts, whether the cancer later recurs, or how participants fare after surgery; the registry lists recurrence-free survival and overall survival separately as secondary outcomes.

The registry record does not report an observed response proportion, the number of responses, or the stated 90% confidence interval. It also does not report the number of participants with evaluable scans. Consequently, the endpoint definition is available, but the response result and its precision cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The available registry entries identify the endpoint definition and the intended confidence-interval level, but do not describe the analysis that produced a result. The registry reports zero analyses and gives no primary response estimate. The concepts below are general explanations of the statistical methods named or relevant to interpreting the outcome; they are not evidence that a particular unreported method was used in this trial.

What does a response percentage represent?

For a binary endpoint, each assessed participant is classified as meeting or not meeting the response definition. The response percentage describes the proportion classified as having a complete or partial response among the participants included in that analysis. Its interpretation depends on the analysis population and denominator. If participants without an evaluable scan are excluded, for example, the percentage answers a different question from an analysis that retains everyone enrolled and assigns an outcome to those with missing scans. The registry record does not state which participants were included or how missing assessments were treated. No denominator or response count is reported.

The outcome definition reduces a measurement to response categories rather than describing the full range of tumor-size changes. As a general matter, categorization can make a result easier to communicate, but it also means that changes that do not cross the response threshold are not counted as responses. The record specifies complete response and partial response, including the partial-response criterion of a decrease of 30% or greater from baseline. It does not report whether imaging was centrally reviewed, how measurements were made, or how ambiguous assessments were resolved.

What does a confidence interval add?

A confidence interval communicates uncertainty around an estimate, rather than giving only a single point estimate. In general, it is calculated using the observed data and a specified statistical procedure. A 90% confidence interval is the dispersion measure named for the primary endpoint in the registry record. Its endpoints are not reported. Without an estimate, interval limits, denominator, and analysis method, the actual precision of the response result cannot be assessed. A confidence interval also does not correct for limitations of the study design, such as the lack of a concurrent comparator.

For a percentage based on a binary outcome, the method used to construct the interval matters, particularly when the number of events or participants is limited. General methods can differ in how well they perform in different data settings. The registry record does not state which interval procedure was planned or used, so no particular method should be attributed to this trial.

Why does the single-group design matter?

In a single-group study, the observed outcome describes what happened among participants receiving the intervention and included in the analysis. There is no concurrent randomized group to provide a direct estimate of what would have happened over the same period under a different treatment assignment. General sources of uncertainty include participant selection, natural changes in disease, variation in measurement, and other care received. These concerns do not make a single-group response estimate meaningless; they define what it can and cannot establish. Without an analysis result, even the descriptive response proportion is unavailable in this record.

Randomization is useful in comparative studies because it can make treatment groups comparable in expectation. This trial is not recorded as randomized and has no control arm, so a treatment contrast is not available. Statistical adjustment cannot be assumed to create a randomized comparison, and the registry record does not report an adjusted analysis.

How should planning calculations be read?

The registry describes sample-size assumptions as planning illustrations computed from an observed effect, rather than the trial’s own design. It names a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, and states that the effect to detect is a stated fraction of the observed effect. Those assumptions describe hypothetical planning for a two-arm setting; they do not describe the actual single-group allocation recorded for this trial.

In general, a sample-size calculation asks how many participants per arm might be needed under specified assumptions to detect a chosen effect with a chosen power. Such calculations are planning tools, not observed outcomes. They are not observed power, and they do not show that the trial achieved a particular precision or that an effect was present. The record does not provide a protocol sample-size justification. It also does not provide a primary result from which a reader could evaluate the observed effect used in a planning illustration.

The stated assumptions include equal allocation between two arms, even though this trial is a single-group study. The planning illustration therefore should not be read as a comparison actually performed in the trial. No numeric planning outputs are reported in the registry record, and none can be interpreted as trial findings.

What does the record say about analyses?

The registry record identifies the primary outcome and lists secondary outcomes, but reports no analyses. It does not identify an analysis population, a missing-data method, an adjustment strategy, or a prespecified model for the primary endpoint. These omissions prevent assessment of whether the endpoint was analyzed as planned, how incomplete data affected the estimate, or whether any sensitivity analyses were performed. No particular statistical test or model should be inferred from the endpoint label alone.

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")
n      <- c(24)
events <- c(7)
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  24  7  29.2  12.6  51.1  14.9  49.2  14.9  49.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary outcome as objective response rate and lists recurrence-free survival, overall survival, postoperative complications of any grade, and high-grade surgery-related complications as secondary outcomes. It reports five outcome measures and zero analyses. The record does not describe a multiplicity strategy, such as a prespecified hierarchy or adjustment for testing several outcomes. It is therefore not reported in the registry record whether the results were intended to support a single primary inference or how interpretation across outcomes was planned.

In general, examining multiple outcomes can increase the chance that at least one result appears notable by chance. Statistical approaches to multiplicity can address that concern, but the registry record does not state that any such approach was used. No conclusions about adjustment or confirmatory status can be drawn from the outcome list alone.

The record does not describe missing-data handling for the primary endpoint or secondary outcomes. It does not report how missing scans, incomplete follow-up, treatment discontinuation, or unavailable complication information were handled. It also does not identify the analysis population for the response estimate. These details matter because the people included in an analysis determine the population to which its estimate applies.

Enrollment is reported as 39, while the adverse-event figures list 24 participants at risk in each grouping. The registry record does not explain this difference in reporting contexts or identify the primary endpoint denominator. The figures should not be combined or used to infer the number with complete response data. The record also does not report whether participants were excluded from any outcome analysis or why.

12. 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 4% reporting threshold.

Most frequent non-serious adverse event terms

The safety figures list the Axitinib group with 24 participants at risk for serious adverse events and zero affected. The same group is listed with 24 at risk for other adverse events and 19 affected. Deaths are reported as zero. These are descriptive counts in the registry record, not comparative estimates.

The two adverse-event groupings are presented separately. The record does not provide serious adverse-event terms, and the list of top serious terms is empty. It does not give event-level details, timing, severity distributions beyond the stated grouping, or a method for attributing events to treatment. The count of 19 affected by other adverse events does not identify the types of events or their clinical importance.

In general, a count of participants affected is not necessarily a count of total events: one participant can experience more than one event. The registry figures are participant counts, and the record does not provide total event counts. The enrollment figure is 39, but the safety denominators are 24; the record does not explain their relationship. These safety figures cannot be treated as a complete description of safety for everyone enrolled or as a comparison with another group.

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

The registry record establishes that a Phase II, single-group study evaluated neoadjuvant axitinib for locally advanced clear cell renal cell carcinoma, with objective response after 12 weeks as the primary endpoint. It defines response using complete and partial response categories based on RECIST v1.0. It also lists recurrence-free survival, overall survival, and postoperative complication outcomes.

The record does not report the primary response count, response percentage, or 90% confidence interval. It reports zero analyses. Thus, these registry entries do not show what proportion of participants had a response, how precise an estimate was, or how the secondary outcomes turned out. A study marked completed is not, by itself, evidence of a particular clinical outcome.

Even if a response estimate were available, the single-group design would make it a description of outcomes in the treated group, not a randomized estimate of the effect relative to a comparator. In general, without a concurrent control group, observed changes cannot be separated from other influences as they can be in a well-conducted randomized comparison. The design also cannot establish from the response proportion alone whether responses were durable or how participants fared after the assessment; those questions relate to other outcomes listed in the registry.

The safety figures report zero participants affected by serious adverse events among 24 at risk, 19 affected by other adverse events among 24 at risk, and zero deaths. They are limited to the registry’s listed groupings and do not give detailed event descriptions. The record does not explain why the safety denominators differ from the enrollment figure, so these counts should be interpreted with that reporting limitation in mind.

Overall, the registry record provides the study question, treatment description, endpoint definition, design, and selected safety counts. It does not provide outcome analyses sufficient to judge the observed response or its uncertainty. It also does not support a comparative treatment-effect conclusion.

14. Why This Trial Matters Statistically

This trial is statistically notable for the contrast between a clearly defined primary endpoint and the absence of a reported endpoint result in the registry record. The response definition is specific: it identifies the imaging time point and the complete and partial response criteria. Those features make clear what outcome was intended to be measured. However, an endpoint definition does not reveal the observed response rate or its precision. The record reports zero analyses, leaving the central statistical estimate unavailable.

The single-group design also matters for interpretation. It can describe outcomes among participants who received axitinib, if an analysis is reported, but it does not supply a randomized comparison. This distinction is important when readers encounter response language: a response proportion is a descriptive statistic, whereas a treatment effect requires a comparison or other defensible counterfactual approach. No comparative estimate is reported in the registry record.

The safety reporting illustrates a further statistical issue: denominators must be tied to the outcome being described. Enrollment is listed as 39, while the adverse-event groupings list 24 at risk. Because the registry record does not explain the relationship, readers cannot assume that every outcome uses the same analysis population. Reporting the denominator alongside each count is essential for understanding what the count represents, but the available record does not resolve why the denominators differ.

Finally, the listed planning assumptions should not be mistaken for the trial’s design or evidence about its outcome. They describe a hypothetical two-arm planning setting, while the actual trial is recorded as single group. Planning calculations may help researchers explore future study requirements, but they do not replace observed estimates, uncertainty intervals, or a transparent account of missing data and analysis populations.

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 primary limitation for interpretation is that the registry record does not report an objective response result, despite identifying objective response rate as the primary outcome. No response count, percentage, or confidence interval is available, and the record reports zero analyses. This prevents assessment of the observed endpoint and its precision.

The single-group design has no concurrent control group. Any eventual response estimate would be descriptive of the analyzed participants and would not directly quantify a contrast against another treatment. The registry also lists no masking, so outcome assessment was not masked according to the record. It does not report whether imaging review was independent or centrally adjudicated.

The enrollment figure is 39, but the safety record uses 24 participants at risk for each adverse-event grouping. The record does not explain this difference, and it does not state the primary endpoint denominator. It is not possible to determine from the record whether the figures reflect different populations, follow-up availability, or another reporting convention.

Eligibility details, participant characteristics, treatment adherence, dose changes, surgery timing, and handling of incomplete imaging are not reported in the registry record. Nor are statistical methods for the response estimate, missing-data procedures, analysis populations, or multiplicity strategy. The secondary outcomes are named but no results are reported. These gaps limit assessment of selection, data completeness, outcome ascertainment, and the breadth of results available for interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Neoadjuvant Axitinib in Locally Advanced Renal Cell Carcinoma (RCC) — NCT01263769.
• Registry record last updated 2024-09-19; status last verified 2024-08.
• Results first posted 2022-02-03.
• 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 study of neoadjuvant axitinib in locally advanced clear cell renal cell carcinoma. Enrollment is listed as 39. The starting dose was 5 mg by mouth twice each day for 12 weeks. The primary endpoint was objective response rate assessed by CT abdomen after 12 weeks, using RECIST v1.0 complete and partial response criteria.

The record lists recurrence-free survival, overall survival, and postoperative complication outcomes as secondary outcomes. It reports zero analyses and does not provide a primary response estimate or confidence interval. Safety figures list zero serious adverse events among 24 at risk, 19 participants with other adverse events among 24 at risk, and zero deaths. The registry record does not explain the difference between the enrollment and safety denominators or report detailed serious adverse-event terms.