A Pivotal Study Of SU011248 In The Treatment Of Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pivotal Study Of SU011248 In The Treatment Of Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma. (NCT00077974), a non-randomized phase 2 study. The primary outcome is Number of Subjects With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST).

2. Clinical Question

This is a question about observed tumor response in a defined study population, not a randomized estimate of the difference between treatments. A confirmed response requires the response category to be confirmed; the registry defines complete response as disappearance of all target lesions and partial response as at least a 30 percent decrease in the sum of the longest dimensions of target lesions, relative to baseline. The endpoint thus combines two categories into a count of participants with either category.

The record also names time to tumor progression, duration of response, overall survival, and progression-free survival among its secondary outcomes. These address different aspects of disease course: whether a response occurred is not the same question as how long it lasted or how long participants remained alive or free of progression. Their results are not reported in the registry record.

3. Trial Design

NCT00077974 is listed as a phase 2 study of SU011248 in patients with cytokine-refractory metastatic renal cell carcinoma. Its stated purpose was to assess safety and efficacy in patients with metastatic, refractory renal cell carcinoma. The registry lists Pfizer as sponsor, an enrollment of 106, a start date of 2004-02, a primary completion date of 2008-09, and a completed status.

The design is non-randomized, unmasked, and single-group. Those features mean the record describes treatment in one study group rather than an allocation between study treatment and a concurrent randomized control. No masking was used. Because there is no like-for-like randomized control group, the design does not directly estimate a treatment contrast that would separate treatment effects from differences in patient characteristics, natural disease course, or other influences.

The intervention is listed as SU011248, a drug. The primary endpoint concerns confirmed objective response according to RECIST. The primary assessment timeframe begins at the start of study treatment and includes Day 28 of Cycles 1-5 and Day 28 of even cycles thereafter. The record lists 12 outcome measures and one analysis, but does not report enough detail to explain the scope or statistical specification of that analysis.

The intent-to-treat population is defined in the record as all subjects enrolled who received at least one dose of study medication. It is identified as the primary population for efficacy and safety analyses. The actual number meeting that definition is not reported in the registry record. Details of dosing, treatment duration, eligibility criteria beyond the described disease setting, and study procedures are not reported in the registry record.

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: The intent-to-treat (ITT) population included all subjects who enrolled in the study that received at least 1 dose of study medication. This was the primary population for all efficacy analyses and safety analyses.

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 Number of Subjects With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST), measured over From start of study treatment until Day 28 of Cycles 1-5, Day 28 of even Cycles thereafter.

The primary endpoint is the number of participants with a confirmed objective response according to RECIST. It counts participants whose best qualifying response was a confirmed complete response or confirmed partial response. A complete response is defined as disappearance of all target lesions. A partial response is defined as at least a 30 percent decrease in the sum of the longest dimensions of target lesions, using the baseline sum as the reference.

This is a binary participant-level outcome: each participant either meets the stated confirmed-response definition or does not. Summarizing the outcome as a count can make a tumor-shrinkage endpoint easier to interpret than presenting only a continuous measurement, while the confirmation requirement makes the endpoint depend on confirmation rather than a single unconfirmed observation. The registry does not specify further rules for handling unevaluable assessments or missing scans.

RECIST response is used to describe measurable tumor change under prespecified criteria. It does not, by itself, describe how long a response lasts or whether participants live longer. The registry lists duration of response, time to tumor progression, progression-free survival, and overall survival as separate secondary outcomes, reflecting those distinct questions. The primary response count and its uncertainty are not reported in the registry record, so the magnitude and precision of the observed response rate cannot be assessed from the information available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation starts with the type of endpoint. The primary measure is a count of participants who had a confirmed response, rather than a continuous measurement such as a change in tumor dimensions or a time-to-event estimate. For a binary outcome, each participant is classified according to whether the response definition was met. A response proportion can be estimated by relating the number who responded to the number assessed in the analysis population. The registry record does not report the response count or the number assessed, so such an estimate cannot be stated.

What does confirmation add?

General explanation: confirmation means that a response classification must satisfy the study's confirmation rule rather than being based solely on an initial observation. This can reduce reliance on a temporary or unverified change, but the exact timing and operational details of confirmation matter. The registry describes the response as confirmed and provides an assessment schedule, but further confirmation rules are not reported in the registry record. The endpoint combines complete and partial response, with the categories defined using RECIST criteria.

What does a confidence interval tell a reader?

General explanation: a confidence interval expresses statistical uncertainty around an estimated quantity. For a response proportion, it would help readers judge whether the estimate is precise or compatible with a broad range of underlying response frequencies. It does not correct for bias in study design, missing outcome data, or differences between the study group and a population of interest. No confidence interval for the primary endpoint is reported in the registry record. A point estimate alone, if it were reported, would not convey this uncertainty.

Why is the single-group design important?

General explanation: random allocation to concurrent groups can make treatment groups more comparable on average, supporting a treatment contrast. In a single-group study, there is no randomized comparator to provide that contrast. The observed outcome can be described, but causal interpretation is limited because other influences on outcomes are not separated by randomization. This study is listed as non-randomized and single-group, and the record notes that its arms are not a like-for-like control comparison. It would therefore be inappropriate to interpret a one-group response frequency as a randomized estimate of benefit relative to another treatment.

How should the analysis population be understood?

The record defines the intent-to-treat population as enrolled subjects who received at least one dose of study medication and identifies it as the primary population for efficacy and safety analyses. The phrase intent-to-treat is therefore being used with that specific definition in this record. The number who met the definition is not reported. Nor are the numbers with missing or unevaluable response assessments. Without those counts, readers cannot determine from the record whether the analyzed population matched enrollment or how incomplete outcome ascertainment may have affected the endpoint.

What can be said about the analysis plan?

The record lists one analysis, but the statistical methods for the primary endpoint are not reported in the registry record. In particular, the record does not specify a planned hypothesis test, a confidence-interval method, adjustment for prognostic factors, or a model for the primary response outcome. These omissions should not be filled by assuming a conventional method. General explanation: a prespecified method helps clarify how the estimate and uncertainty were to be calculated and reduces room for choosing an analysis after seeing results. The record does not provide enough information to assess those choices.

How do the planning illustrations differ from trial results?

The sample-size planning assumptions describe an illustration based on an observed effect, not the design of this trial. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The record says that non-time-to-event planning values are participants per arm, while time-to-event planning values are total events. These are planning conventions and do not constitute observed power. They also do not turn this single-group study into a two-arm randomized trial. The primary observed effect needed to interpret such an illustration is not reported in the registry record.

General explanation: power is a design quantity describing the chance that a specified analysis will detect a specified effect under assumed conditions. It is not a measure of whether a result is true, and calculating power after observing a result does not resolve uncertainty in that result. A sample-size illustration is useful only in relation to its assumptions and target effect. Since the record does not report the primary response result or its uncertainty, those planning assumptions cannot supply the missing efficacy evidence.

The record also names survival and progression outcomes. General explanation: time-to-event methods account for both the time until an event and the fact that some participants may not have had the event by the end of observation. Their interpretation depends on outcome definitions, follow-up, censoring rules, and analysis methods. Those details and the results for the listed time-to-event outcomes are not reported in the registry record. No estimate or conclusion about those outcomes can be reconstructed from their names 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("Sunitinib Malate")
n      <- c(106)
events <- c(35)
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  Sunitinib Malate  106  35  33.0  24.2  42.8  24.8  42.4  24.8  42.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures, including the primary confirmed-response endpoint and secondary outcomes for progression, response duration, survival, and plasma trough concentrations. It lists one analysis. The relationship between that analysis and the outcome measures is not explained in the registry record. A list of multiple outcomes does not, by itself, show that each was tested or that any particular statistical adjustment was used.

Multiplicity arises when several statistical questions are examined; without an appropriate plan, the chance of at least one apparently notable result can increase. General explanation: methods such as prespecifying one primary question, controlling an overall error rate, or treating secondary results as exploratory can help readers understand the strength of evidence across multiple analyses. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or which outcomes were formally tested. It is therefore not possible to assess how multiplicity was handled.

Missing-data methods are also not reported in the registry record. The record defines the intended efficacy and safety population as enrolled subjects who received at least one dose, but does not state how missing scans, unevaluable assessments, or withdrawals were handled for the primary endpoint. The number with an assessed primary outcome is not reported. No imputation method, sensitivity analysis, or missingness summary is reported in the registry record.

The population definition is important because the denominator for a response proportion depends on who was included and how unavailable outcomes were treated. Enrollment is listed as 106, but the record does not state the number included in the defined analysis population or the number with evaluable response data. The record also does not report protocol deviations or analysis-population sensitivity checks. These gaps limit assessment of both the representativeness of the analyzed group and the potential influence of missing outcome information.

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: disease progression (6.6%), dehydration (4.7%), pneumonia (2.8%), renal failure (2.8%), anaemia (1.9%).

The registry lists a Sunitinib Malate group with 106 subjects at risk for serious adverse events and 46 subjects affected. These are the group-level counts recorded for serious adverse events. The record also lists these serious-event terms and percentages: disease progression, 6.6%; dehydration, 4.7%; pneumonia, 2.8%; renal failure, 2.8%; anaemia, 1.9%; and acute myocardial infarction, 1.9%. The denominator underlying each listed percentage is not reported in the registry record.

These figures describe safety events recorded in the study; they are not a comparison of event rates between randomized groups. The study is single-group and non-randomized. A serious adverse event is not necessarily an event caused by the study drug, and these figures alone do not establish causality. The registry information does not report a causal assessment or the clinical circumstances for each event.

The record also gives a separate at-risk count for other adverse events, but its affected count should not be interpreted as the serious-event count. A death count is not reported in the registry record. The listed serious-event percentages should be read as registry-reported figures, not as a complete safety profile or a direct estimate of comparative risk.

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

The trial addresses whether participants in a single study group experienced confirmed tumor response under RECIST criteria. The registry record identifies the target population, study drug, response definition, assessment schedule, and intended efficacy population. It does not report the primary response count, the number assessed, or a response estimate. As a result, the posted information does not show the observed frequency or precision of the primary endpoint.

A confirmed complete or partial response is one particular measure of tumor change. It is distinct from duration of response, progression-free survival, time to tumor progression, and overall survival, all of which are listed as secondary outcomes. A response count cannot stand in for those outcomes, and their results are not reported in the registry record. Likewise, the existence of a defined endpoint does not itself establish that an endpoint was achieved by any particular number of participants.

The single-group design permits descriptive reporting of outcomes in the study group, but does not provide a randomized treatment comparison. General explanation: observed outcomes in one group can reflect treatment, participant characteristics, disease course, assessment practices, and other influences. A concurrent randomized comparator is one design tool for separating treatment groups from those influences. This trial is listed as non-randomized and single-group, so causal claims based on a treatment contrast are not supported by its design.

The serious-event figures provide limited safety information, including 46 affected subjects among 106 at risk in the Sunitinib Malate group and percentages for several listed terms. They should not be interpreted as proof that treatment caused those events or as a comparative safety estimate. More detailed context, including the denominator for the event-term percentages, is not reported in the registry record.

In short, the record documents a phase 2 study question and design, but the primary efficacy result and many details needed to assess the analyses are not reported in the registry record. It supports neither a numerical interpretation of the response endpoint nor a randomized comparison of treatment effects.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a clearly defined endpoint and a reported result. The registry specifies a confirmed RECIST response measure, the response categories, an assessment schedule, and a target analysis population. Those details clarify what the primary question was intended to measure. But without the response count, analysis denominator, or uncertainty estimate, readers cannot quantify the answer to that question.

The design also demonstrates why study structure shapes interpretation. A single-group study can describe outcomes among treated participants, while a randomized comparator is needed for a direct randomized contrast. The registry identifies the study as non-randomized and single-group, so descriptive response and safety summaries should not be mistaken for controlled treatment effects. That distinction is central when interpreting outcomes in clinical research.

The record lists a broad set of outcomes, including response, progression, survival, and drug concentration measures. These endpoints answer different questions and require different statistical summaries. A tumor-response count does not convey the timing or duration of events, while time-to-event outcomes require information about follow-up and censoring. Those results and methods are not reported in the registry record.

Finally, the listed serious adverse-event counts show why safety summaries also require careful context. Counts and percentages need clear denominators, consistent definitions, follow-up information, and appropriate caution about causation. The registry supplies some event figures but does not report all of those details. The statistical lesson is not a clinical conclusion; it is that interpretable evidence depends on both the outcome definition and sufficiently complete reporting of results and methods.

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 interpreting efficacy is that the confirmed-response result is not reported in the registry record. The record does not give the number of responders, the number assessed, a response proportion, or an uncertainty interval. Enrollment is listed as 106, but that does not establish the number included in the defined efficacy population or with an evaluable primary outcome.

The non-randomized, single-group design has no concurrent randomized control group. It therefore does not support a like-for-like randomized treatment comparison. Any descriptive outcomes would need to be interpreted in light of the absence of such a comparator and the possibility that factors other than study treatment influenced the observed results.

Further limitations arise from unreported analysis details. The statistical plan for the primary endpoint, handling of missing or unevaluable assessments, multiplicity approach, and sensitivity analyses are not reported in the registry record. Although the population definition is stated, the actual analysis-population count is not. The registry also does not explain the listed single analysis or its relation to the 12 outcome measures.

For safety, the serious-event group counts and selected percentages are available, but the denominator for the listed event-term percentages and a causal assessment are not reported in the registry record. Details such as follow-up duration for safety events and the death count are also not reported. These limitations prevent a complete assessment of efficacy, precision, and comparative safety from the registry information alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Pivotal Study Of SU011248 In The Treatment Of Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma. — NCT00077974.
• Registry record last updated 2010-10-13; status last verified 2010-10.
• Results first posted 2009-11-03.
• 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

NCT00077974 is a completed phase 2, non-randomized, unmasked, single-group study sponsored by Pfizer. It lists an enrollment of 106 and evaluates SU011248 in patients with cytokine-refractory metastatic renal cell carcinoma. The primary endpoint is the number of participants with confirmed complete or partial response according to RECIST, assessed on a cycle-based schedule.

The registry defines the intent-to-treat population as enrolled subjects who received at least one dose and identifies it as the primary population for efficacy and safety analyses. The primary response result, actual analysis-population count, and statistical methods are not reported in the registry record. Serious adverse-event figures are listed for the Sunitinib Malate group, but they do not constitute a randomized comparison or establish causation.