Sunitinib Malate After Stereotactic Radiosurgery in Treating Patients With Newly Diagnosed Brain Metastases: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sunitinib Malate After Stereotactic Radiosurgery in Treating Patients With Newly Diagnosed Brain Metastases (NCT00910039), a na phase 2 study. The primary outcome is Central Nervous System (CNS) Progression-free Survival Rate.

2. Clinical Question

The study was designed to examine sunitinib malate after SRS in people with newly diagnosed brain metastases. The primary endpoint focuses on being alive and free of progressive disease in the brain at the specified follow-up point. It is a count of participants, not a treatment-versus-control effect estimate. Because the trial has one group, its results cannot by themselves establish how outcomes would have differed under another treatment or under no maintenance therapy.

The record also lists secondary outcomes covering CNS progression-free survival, time to CNS disease progression, overall survival, time to progression, local failure, neurocognitive effects, and safety and tolerability. These describe additional questions the study intended to examine. The registry record does not report results for these measures, nor does it report analyses for them.

3. Trial Design

This was a phase II, single-group study sponsored by Case Comprehensive Cancer Center. The registry lists an enrollment of 14 and a status of terminated. The recorded start is 2009-04, and primary completion is recorded as 2012-01. The registry record does not explain why the study was terminated or provide further detail about the timing of termination.

The intervention was sunitinib malate after SRS. The arm description specifies oral dosing once daily on days 1-28, with courses repeating every 42 days while there was no disease progression or unacceptable toxicity. No dose amount is reported in the record excerpt. Participants were also to undergo neuropsychological battery testing at baseline and periodically during the study to assess cognitive function; the description is truncated before listing all cognitive domains.

Allocation is listed as not applicable, masking as none, and the model as single group. This means the posted design is not a randomized comparison and does not include a like-for-like control arm. The absence of a control group is central to interpretation: observations in the treatment group can describe what was recorded among participants, but they do not isolate the effect of sunitinib from other explanations for those observations.

The registry lists the primary outcome as the number of participants meeting a CNS progression-free survival condition at six months after SRS. The designated population is intent to treat. The listed secondary outcomes include survival, progression, local failure, neurocognitive effects, and safety and tolerability. Although the record identifies these intended outcomes, it does not report their observed values.

There is no reported sample-size justification, detailed statistical analysis plan, or explanation for the termination in the registry record. The planning calculations shown elsewhere on the page should therefore be read as illustrations rather than as the documented basis for the original trial design.

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: Intent to treat

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 Central Nervous System (CNS) Progression-free Survival Rate, measured over 6 months after stereotactic radiosurgery (SRS).

The primary endpoint is recorded as the number of participants who survived at least six months from SRS without progressive disease anywhere in the brain, including local or regional failure. The registry labels the outcome as a CNS progression-free survival rate, but specifies the measure as a number of participants. The result would therefore be a count for the intent-to-treat population rather than, in the endpoint description, a reported comparison between treatment groups.

Progression was assessed using McDonald's standard criteria. The description includes progressive neurologic abnormalities not explained by causes unrelated to tumor progression, with examples such as anticonvulsant or corticosteroid toxicity, electrolyte abnormalities, and hyperglycemia. It also includes a greater than 25% increase in tumor size on MRI or CT scan.

In general, a time-specific endpoint can summarize whether participants have reached a clinically relevant state by a defined follow-up point. Here, combining survival with absence of brain progression makes the endpoint broader than imaging change alone. However, a count at the specified time does not show the timing of events outside that definition or describe the pattern of change over the full follow-up period.

The registry record does not report the observed number meeting the endpoint, the denominator used in any reported result, or an uncertainty interval. It also does not report how participants with missing follow-up or incomplete assessment were handled. Without those results and details, the endpoint’s observed value and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help explain what the registry record can and cannot establish. The following discussion is general and does not assume a statistical plan beyond what the record states.

What does a single-group design estimate?

A single-group study observes outcomes among participants receiving the study intervention. Its direct descriptive target is the outcome in that group under the conditions recorded. Without a concurrent comparator, it does not estimate a randomized difference between intervention and control. This distinction is important even when the endpoint is defined clearly and follow-up is planned. Comparisons with external expectations would require additional assumptions and information that are not reported in the registry record.

Here, allocation is listed as not applicable, masking as none, and the model as single group. The record gives no basis for treating the study as a controlled efficacy comparison. The enrollment of 14 describes how many participants were enrolled; it does not, on its own, tell us how precise any endpoint estimate would be. Precision depends on the observed data and the analysis, and the endpoint results are not reported.

How should the primary endpoint be understood?

The endpoint is a count of participants who meet a combined condition: survival for at least six months after SRS and no progressive disease anywhere in the brain under the stated criteria. A count answers how many met that definition only when the observed count is reported. The title’s use of the word rate does not change the registry’s stated parameter, which is a number of participants.

In general, a confidence interval describes uncertainty around an estimate using a specified statistical method. It is not a guarantee that the true value lies inside the interval, nor does it correct for design limitations. No interval for the primary endpoint is reported in this registry record. Without the outcome count and its uncertainty, the precision of the result cannot be evaluated.

Why do time-to-event outcomes need different methods?

Some listed secondary outcomes concern time to CNS disease progression, overall survival, or time to progression. In general, time-to-event methods account for both the event and the length of observation, including participants whose event has not been observed by the end of follow-up. Such participants may be censored rather than treated as if their event never occurred. The registry record names these outcomes but does not report their results, censoring details, or the methods used to analyze them.

For that reason, a time-to-event result cannot be reconstructed from the endpoint list or enrollment alone. It would require the relevant participant-level follow-up information or a reported analysis. The registry record does not supply those data in the material.

What do the planning illustrations mean?

The page includes calculated planning illustrations based on an observed effect and stated assumptions. These are not observed power and are not evidence that the original trial was designed with those assumptions. The described calculations use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and a fraction of the observed effect as the effect to detect. Time-to-event illustrations express total events; other illustrations express participants per arm.

Those assumptions describe a hypothetical two-arm planning exercise, whereas this registered study is single group and has no concurrent comparator. The illustrations therefore should not be read as the actual trial design or as the number of participants the study needed. No sample-size justification for the trial is reported in the registry record. Any values displayed in planning tables are illustrative calculations, not observed results or a claim about the trial’s actual power.

Why can over-dispersion matter?

In general, count outcomes can vary more across participants or groups than a simple model assumes. This is called over-dispersion. If present and ignored, uncertainty estimates from some count models can be too small, making results appear more precise than they are. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report a count-model analysis or an assessment of over-dispersion, so no claim can be made about its presence or handling in this trial.

Likewise, statistical significance, confidence intervals, and model assumptions can only be interpreted in relation to a reported analysis. The registry record lists no analyses and does not report a statistical plan. The endpoint definitions are useful for understanding the intended measurements, but they cannot substitute for the missing outcome estimates and analysis details.

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(14)
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  Sunitinib Malate  14  7  50.0  23.0  77.0  26.8  73.2  26.6  73.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and several secondary outcomes, spanning CNS progression, survival, local failure, neurocognitive effects, and safety. Examining multiple outcomes can raise a general multiplicity question: when many hypotheses are tested, the chance of at least one apparently notable result may increase. Statistical plans sometimes address this through a prespecified hierarchy, adjustment, or clearly exploratory interpretation. The registry record does not report whether any such approach was planned or used, so no adjustment strategy should be assumed.

The record lists 0 analyses and does not report outcome estimates for the primary or secondary measures. It therefore does not provide results from which to assess multiplicity in practice, or to distinguish confirmatory findings from exploratory ones. The planned outcome list alone cannot show which measures were analyzed or whether there were additional analyses.

Missing-data handling is also not reported in the registry record. The primary population is identified as intent to treat, but the record does not state how participants with missing six-month assessments, incomplete imaging, withdrawal, or unavailable follow-up were treated in the endpoint analysis. Intent-to-treat terminology does not by itself explain how missing outcome data were handled.

The registry record does not report interim analyses, imputation methods, sensitivity analyses, or a detailed analysis population definition beyond the primary population label. These omissions limit assessment of the robustness of any estimate, particularly if follow-up or assessment was incomplete. They should be understood as information not reported in the registry record, not as evidence that a particular method was or was not used outside the 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lymphopenia (14.3%), diarrhea (14.3%), neutrophils/granulocytes (anc/agc) (7.1%), cardiac troponin t (ctnt) (7.1%), vomiting (7.1%).

The adverse-event figures describe the Sunitinib Malate group, with 14 participants at risk in the serious-event and other-event categories. The record reports 7 participants affected in the serious-event category and 14 affected in the other-event category. These are descriptive counts for this group, not comparisons against a control group. The record does not report deaths in the relevant field.

The selected serious adverse-event terms and their reported percentages are lymphopenia, 14.3%; diarrhea, 14.3%; neutrophils/granulocytes (ANC/AGC), 7.1%; cardiac troponin T (cTnT), 7.1%; vomiting, 7.1%; and hemorrhage, CNS, 7.1%. These are the terms listed in the registry record. They should not be treated as estimates of comparative risk or as proof of a causal relationship.

In general, adverse-event summaries depend on how events were defined, collected, coded, and counted. The registry figures alone do not explain event severity beyond the serious-event classification, timing, duration, recurrence, or relationship to treatment. Nor do they provide a comparison group. The figures are useful as a record of reported safety observations, but the registry record does not provide enough information to interpret them as comparative evidence.

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

The record establishes that a phase II, single-group study examined sunitinib malate as maintenance therapy after SRS in people with newly diagnosed brain metastases. It defines a primary endpoint based on survival and brain progression at six months after SRS, identifies an intent-to-treat population, and lists additional outcomes. It also includes descriptive adverse-event information for the treatment group.

These registry entries describe the study question and reporting structure. They do not show the observed primary endpoint result. The registry record does not report how many participants met the primary definition, and it does not report results for the secondary outcomes. It is therefore not possible from this record to describe the observed CNS progression-free survival outcome, the timing of progression, overall survival, neurocognitive findings, or the overall safety pattern beyond the listed adverse-event figures.

The single-group design also places a limit on what any reported outcome could mean. In general, an outcome observed after treatment is not automatically an estimate of the treatment’s effect. Without a concurrent comparator, the study cannot separate the treatment strategy from other influences on outcomes. The record does not establish what would have happened to a comparable group under a different strategy.

The status is recorded as terminated, but the reason is not reported in the registry record. It should not be interpreted as evidence for or against a treatment effect or safety concern. The record also does not report a sample-size justification, interim analyses, or a detailed statistical plan. Their absence from the registry record leaves those aspects uncertain.

In short, the posted record supports a description of the trial design, its intended endpoint and selected safety reporting. It does not provide the outcome results needed to determine the observed primary endpoint or assess its precision. No clinical conclusion about treatment benefit or lack of benefit follows from the information recorded.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its primary endpoint has a clear time point and clinical definition, while its design has no concurrent control group. The combination makes it useful to distinguish endpoint description from causal comparison. A carefully specified outcome answers what investigators intended to count; it does not, by itself, show whether the intervention changed outcomes.

The registry also illustrates why the endpoint’s measurement scale matters. Although the outcome title uses the word rate, the registered parameter is a number of participants. A count, a proportion, and a time-to-event estimate answer different questions and require different reporting. Here, the record does not include the observed count or an uncertainty measure, so neither the endpoint’s magnitude nor its precision can be evaluated.

The record lists a broad set of secondary outcomes. In general, multiple outcomes create questions about how analyses are prioritized and how uncertainty is interpreted. Because the analysis plan and results are not reported, readers cannot determine whether any outcome was confirmatory or exploratory, or whether multiplicity was addressed.

Finally, the planning illustrations on the page are not interchangeable with the study’s actual design. Their stated assumptions describe a hypothetical two-arm calculation, while this trial is single group. This contrast emphasizes that a sample-size calculation is meaningful only in the context of its assumptions and intended comparison. The registry record does not report the original sample-size rationale, and the enrollment alone cannot substitute for it.

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 main limitation for interpreting this trial from the registry record is that outcome results are not reported. The primary endpoint is defined, but its observed count and uncertainty are absent. The listed secondary outcomes likewise have no reported results in the record excerpt. This prevents assessment of outcome magnitude, precision, or consistency across endpoints.

The design is single group, with allocation listed as not applicable and no masking. There is no concurrent control arm for a like-for-like comparison. As a result, even a reported outcome would be descriptive and would not, on its own, establish what difference was attributable to the intervention. This is a design limitation rather than a specific outcome finding.

Enrollment is listed as 14 and the study status as terminated. The reason for termination is not reported in the registry record. The record also does not give a sample-size justification, detailed statistical plan, interim analysis information, or an explanation of how missing outcomes were handled. It does not report follow-up completeness, endpoint analysis details, or sensitivity analyses.

The arm description is truncated, so it does not give a complete account of all cognitive domains or study procedures in the material. The registry identifies cognitive assessment and several neurocognitive outcomes, but it does not report their results. Safety reporting includes selected serious-event terms and participant counts, but not enough detail to assess event timing, duration, attribution, or comparative risk.

Together, these limitations mean that the record can support a careful description of the intended study and the safety figures listed, but not a complete evaluation of efficacy, precision, or the reasons for termination.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sunitinib Malate After Stereotactic Radiosurgery in Treating Patients With Newly Diagnosed Brain Metastases — NCT00910039.
• Registry record last updated 2014-09-29; status last verified 2014-09.
• Results first posted 2013-10-01.
• 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 phase II study evaluated sunitinib malate after SRS for people with 1-3 newly diagnosed brain metastases. It was a single-group trial with no concurrent control arm, no masking, and an enrollment of 14. The record lists the study as terminated.

The primary endpoint was the number of participants alive at least six months after SRS without progressive disease anywhere in the brain, assessed using the stated criteria. The primary population was intent to treat. Secondary outcomes included CNS progression, survival, local failure, neurocognitive effects, and safety and tolerability.

The registry record does not report the primary or secondary outcome results, a sample-size justification, the reason for termination, or detailed missing-data and analysis procedures. It includes descriptive adverse-event counts and selected serious-event terms. The design and reporting limitations mean that the record does not support a treatment-versus-control effect estimate.