A Study to Assess Sorafenib Alone and in Combination With Low-Dose Interferon Following Unsuccessful Treatment With Sunitinib in Patients With Advanced Renal Cell Cancer.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Assess Sorafenib Alone and in Combination With Low-Dose Interferon Following Unsuccessful Treatment With Sunitinib in Patients With Advanced Renal Cell Cancer. (NCT00678288), a randomized phase 2 study. The primary outcome is Progression-Free Survival.

2. Clinical Question

3. Trial Design

This was a phase II, randomized, open-label, multicenter study with a parallel-group design. It enrolled patients with metastatic renal cell carcinoma after unsuccessful first-line sunitinib treatment. The registry record describes unsuccessful treatment as either response followed by progression or intolerance. The recorded enrollment was 16, and the study status is terminated.

The comparison was sorafenib alone versus sorafenib combined with low-dose interferon alpha-2a. The registry describes sorafenib as 400 mg twice daily, continuously, in both arms. In the combination arm, interferon was given at 3 MIU five times a week, subcutaneously, from Monday to Friday, beginning one week after sorafenib. The brief summary also describes a possible increase of sorafenib to 300 mg twice daily for patients who responded and then progressed, if toxicity was acceptable and at the investigator’s discretion. The registry record does not report how often this occurred.

Open-label means that treatment assignment was not masked. A parallel-group design assigns participants to a treatment group and follows those groups during the study. Randomization is intended to reduce systematic differences between groups at assignment, although a small enrollment can leave substantial uncertainty about how comparable the groups are. The registry record does not report the randomization procedure or allocation ratio.

The study began in 2008-04, and primary completion is recorded as 2009-06. These registry dates describe the study record; they do not establish how long each participant was followed. The primary endpoint was progression-free survival, with assessment every 8 weeks over a stated period from the first subject’s treatment start until 14 months later. The registry record says the efficacy analysis was not performed because of low accrual.

The registry lists response rate, time to progression, duration of response, and overall survival as secondary outcomes. It does not report analyses for those outcomes. A statistical analysis plan, target enrollment rationale, and reason for termination 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.

Before assignment: A total of 24 subjects were screened; 16 were enrolled and randomized; 10 (63%) to sorafenib alone and 6 (37%) to sorafenib + interferon. All 16 randomized subjects received at least 1 dose of study drug and were included in the safety analysis population.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy analysis was not performed due to low accrual. For details, please see Limitation and Caveats.

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 Progression-Free Survival, measured over From start of treatment of the first subject until 14 months later, assessed every 8 weeks.

Progression-free survival measures the time from treatment initiation until disease progression or death, whichever occurs first. In this registry record, progression could be identified radiologically or clinically according to RECIST, and death counted if it occurred before progression was documented. This endpoint combines disease progression and death into a time-to-event outcome; it is not simply the proportion of participants who were alive without progression at one selected visit.

The registry says participants without documented progression or death at analysis were censored at the date of their last tumor evaluation. Censoring means that the event time is not observed during the available follow-up, so the participant contributes information up to the last assessment but is not treated as having had an event at that date. Valid interpretation depends on appropriate follow-up and on assumptions about the relationship between censoring and the chance of an event.

Progression-free survival is used in oncology studies to represent the time until worsening of disease or death, and it can use information from across follow-up rather than only a single endpoint visit. The registry scheduled assessment every 8 weeks and gave a study-level assessment period from the first subject’s treatment start until 14 months later. That description does not specify each participant’s follow-up duration.

Although the endpoint is defined, the registry record states that an efficacy analysis was not performed because of low accrual. It therefore reports no progression-free survival estimate or comparison between the treatment groups. The endpoint definition alone does not establish whether either regimen changed progression-free survival.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical trial methods determine how a treatment comparison is planned, measured, and interpreted. The registry identifies this study as randomized, open-label, multicenter, and parallel-group. It also identifies progression-free survival as the primary outcome. However, because the registry says an efficacy analysis was not performed due to low accrual, it does not provide an estimated treatment effect or the statistical results needed to assess that effect.

What randomization contributes

Randomization assigns participants to treatment groups using a chance-based process. Its purpose is to limit systematic differences between groups at the start of a study, including differences that investigators may not have measured. It does not guarantee that groups will be balanced on every characteristic, particularly when enrollment is limited. The registry record does not describe the randomization sequence, allocation concealment, or allocation ratio, so those procedural details cannot be assessed.

A parallel-group design follows participants in their assigned groups rather than having each participant receive both study regimens in sequence. The arms in this trial were sorafenib alone and sorafenib with interferon alpha-2a. The registry describes the study as open-label, meaning masking was absent. Knowledge of assigned treatment can affect care, reporting, or outcome assessment in some circumstances. The record does not report whether or how such effects were addressed.

How a time-to-event endpoint works

Progression-free survival is a time-to-event outcome. Each participant’s observation begins at the specified starting point and ends at progression or death, if either is observed. The registry defines progression using radiological or clinical assessment according to RECIST, with the earlier qualifying event counted, and includes death before documented progression. It describes censoring participants who had neither progression nor death at analysis at their last tumor evaluation.

Time-to-event methods can use the timing of events and account for participants whose event has not been observed by the end of their available follow-up. Censored observations are not equivalent to event-free observations for all future time. Interpretation relies on accurate event dates, sufficiently complete follow-up, and assumptions about censoring. The registry record does not report the analysis method, the number of events, the follow-up distribution, or the number censored.

The record states that tumor assessments were scheduled every 8 weeks and gives a study-level timeframe extending from the first subject’s treatment start until 14 months later. Assessment schedules matter because progression is observed at evaluations rather than necessarily at the exact biological time it begins. The registry does not report adherence to the assessment schedule or the rules used to handle missed or delayed assessments.

What an effect estimate and its uncertainty would show

A comparative analysis would ordinarily quantify how the endpoint differed between the assigned groups, using a method appropriate for the outcome and study design. The estimate would need to be interpreted together with its uncertainty. A confidence interval expresses the range of effects reasonably compatible with the observed data under the model and its assumptions. A p-value addresses how compatible the data are with a specified null hypothesis under the analysis assumptions; it does not measure the size or importance of an effect.

Neither a progression-free survival estimate nor a confidence interval or p-value is reported for this study’s efficacy comparison. The registry lists no analyses. As a result, there is no statistical basis in the posted efficacy record for judging the direction, magnitude, or precision of a treatment difference.

Why accrual and event information matter

Enrollment affects how much information a study can collect, but the number enrolled alone does not determine the precision of a time-to-event comparison. Event counts, follow-up, censoring, and the pattern of outcomes also matter. The registry gives an enrollment of 16 and says low accrual prevented efficacy analysis. It does not report the planned enrollment, an event target, or a sample-size justification. Those design details are not reported in the registry record.

Planning calculations based on an observed effect, when available, are illustrative rather than proof that a study had adequate power. They do not recover a missing efficacy analysis. The registry’s record does not contain an efficacy estimate from which to assess the observed effect for this trial, and it does not report a trial-specific power calculation.

Why over-dispersion can matter generally

Over-dispersion is a general statistical issue that arises when outcome variability is greater than a model assumes. If a model underestimates variability, standard errors may be too small and intervals too narrow. The appropriate approach depends on the outcome and analysis model. The registry record does not report an efficacy model or analyses that would allow assessment of over-dispersion in this study.

Overall, the available methods description is sufficient to identify the randomized, open-label comparison and the intended time-to-event endpoint. It is not sufficient to reconstruct the analysis, verify its assumptions, or quantify comparative efficacy, because no efficacy analysis is reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists progression-free survival as the primary outcome and lists response rate, time to progression, duration of response, and overall survival as secondary outcomes. It also records five outcome measures, but does not provide efficacy analyses. A statistical analysis plan, including any testing hierarchy or adjustment for multiple comparisons, is not reported in the registry record.

Multiplicity arises when a study makes several statistical comparisons or tests several outcomes. The more questions examined, the greater the chance that at least one result may appear unusual under a null model, unless the analysis plan accounts for the testing structure. Without reported estimates or a stated testing plan, there is no basis for assessing whether or how multiplicity was handled. The registry’s list of outcomes does not establish that each was analyzed.

The primary endpoint definition describes censoring at the last tumor evaluation for participants without progression or death at analysis. This gives a general rule for those observations, but the record does not report the number censored, missing assessments, reasons for missing data, or any sensitivity analyses. It also does not report how participants who discontinued treatment or changed treatment were handled in an efficacy analysis.

The registry identifies an efficacy analysis population only by stating that efficacy analysis was not performed due to low accrual. It does not report an intention-to-treat population, a per-protocol population, or other analysis-population definitions. The safety record gives participants at risk for adverse events, but those safety denominators should not be assumed to define an efficacy population.

Missing-data and analysis-population decisions can affect interpretation because they determine which observations contribute to an estimate and how incomplete follow-up is treated. Here, no efficacy estimate is available to evaluate, and details beyond the endpoint’s stated censoring rule are not reported in the registry record.

11. 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: fatigue (33.3%), fracture (16.7%), pain, back (16.7%), infection (documented clinically), bronchus (10.0%), pain, bone (10.0%).

The registry lists serious adverse events for 10 participants at risk in the sorafenib group, with 5 affected, and for 6 participants at risk in the sorafenib-plus-interferon group, with 3 affected. For other adverse events, the corresponding counts are 10 at risk and 9 affected in the sorafenib group, and 6 at risk and 5 affected in the combination group. These are the posted counts; they are not efficacy results.

The registry also lists serious-event terms with percentages: Fatigue, 33.3%; Fracture, 16.7%; Pain, back, 16.7%; Infection (documented clinically), bronchus, 10.0%; Pain, bone, 10.0%; and Dyspnea (shortness of breath), 10.0%. The record does not identify an arm or denominator for each term, so these percentages should not be assigned to a treatment group or interpreted as rates within a particular group.

Counts of participants affected describe how many people had at least one event in the recorded category; they do not indicate the number of separate events or their duration. A serious adverse event is a regulatory category and should not be equated automatically with severity in everyday language. The record does not report event timing, individual-level overlap between categories, or a causal assessment.

These data are descriptive and come from a small enrolled study. They do not establish that either regimen caused or prevented a particular event, and they do not provide a complete comparative safety analysis.

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

This registry record describes a randomized phase II comparison of sorafenib alone with sorafenib combined with low-dose interferon alpha-2a in patients with metastatic renal cell carcinoma after unsuccessful first-line sunitinib treatment. It specifies the intended primary endpoint, progression-free survival, and gives the endpoint definition and assessment schedule. It also posts adverse-event counts and a list of serious-event terms with percentages.

The key limitation for interpreting treatment effects is that the registry explicitly says an efficacy analysis was not performed because of low accrual. No comparative progression-free survival estimate is reported. Nor are results reported for the listed secondary outcomes: response rate, time to progression, duration of response, or overall survival. Therefore, the posted record does not establish the size, direction, or precision of an efficacy difference between the groups.

The absence of an efficacy analysis is not evidence that the treatments had identical outcomes, and it is not evidence that one regimen was superior. It means the registry record does not provide the analysis needed to answer that comparative question. The endpoint’s definition and the trial’s randomized design cannot replace observed outcome estimates.

The adverse-event counts describe participants recorded as affected among those at risk. They can be read as descriptive safety information, but they do not prove that treatment caused an event or establish which regimen has a more favorable safety profile. The serious-event percentages are not linked to an arm or denominator in the record, limiting their interpretation.

The study status is terminated. The registry does not report the reason for termination, a target enrollment rationale, or an efficacy analysis plan. The stated low accrual explains why efficacy analysis was not performed, but the record does not establish why accrual was low or why the trial was terminated. These gaps constrain what can be concluded from the posted results.

13. Why This Trial Matters Statistically

This trial illustrates an important distinction between a study’s intended question and the evidence available to answer it. The randomized design set out to compare sorafenib alone with sorafenib plus interferon alpha-2a after unsuccessful sunitinib treatment. The registry defines progression-free survival as the primary endpoint, but reports that low accrual prevented an efficacy analysis. A clear endpoint and a randomized design do not yield a treatment-effect estimate when the outcome analysis is absent.

It also demonstrates why enrollment and analysis information must be considered together. The registry records enrollment of 16, but does not report an efficacy population, event count, or analysis method. For a time-to-event endpoint, the amount of information depends not only on enrollment but also on events, follow-up, and censoring. Those details are not available in the efficacy record, so precision cannot be assessed.

The study is also a reminder that open-label design is relevant to interpretation. Knowledge of treatment assignment can affect aspects of care or outcome assessment in some settings. That is a general methodological concern, not evidence that bias occurred in this trial. The registry does not report procedures used to minimize or assess such influence.

Finally, the record separates safety reporting from efficacy reporting. It contains counts of participants affected by serious and other adverse events, while providing no efficacy comparison. Readers should not use one type of result as a substitute for the other. Taken together, the record offers information about study design and descriptive safety outcomes, while leaving the intended comparative efficacy question unanswered.

14. 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 most direct limitation is the absence of an efficacy analysis. The registry attributes this to low accrual. Although enrollment is recorded as 16, no primary endpoint estimate, uncertainty interval, or comparative test is posted. The registry also lists secondary outcomes without reporting their analyses.

The record does not report a target enrollment, sample-size justification, or planned number of events. It therefore does not allow assessment of whether the study was designed to achieve a particular level of precision or statistical power. A reason for termination is also not reported in the registry record.

Important analysis details are unavailable, including the efficacy analysis method, the number of progression or death events, follow-up duration by group, the number censored, and the definition of the efficacy analysis population. The endpoint description gives a censoring rule but does not provide enough information to evaluate how it was applied. Missing assessment information and sensitivity analyses are not reported.

The trial was open-label. That design feature can matter for decisions about care, reporting, and assessment, though the registry record does not establish that it affected outcomes. The record also does not describe the randomization procedure or allocation ratio. With limited enrollment, chance imbalance between groups is possible, but group characteristics are not included in the registry entries and should not be inferred.

Safety reporting is also limited. The registry lists affected-participant counts and serious-event terms with percentages, but the percentages are not linked to treatment groups or denominators in the record. Event timing, overlap, and causal attribution are not reported. These limitations mean the safety counts are descriptive and the comparative efficacy question cannot be resolved from the posted record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Assess Sorafenib Alone and in Combination With Low-Dose Interferon Following Unsuccessful Treatment With Sunitinib in Patients With Advanced Renal Cell Cancer. — NCT00678288.
• Registry record last updated 2014-12-11; status last verified 2014-11.
• Results first posted 2010-10-01.
• 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.

18. Record Summary

The registry record identifies NCT00678288 as a terminated phase II, randomized, open-label, multicenter, parallel-group study sponsored by Bayer. It enrolled 16 patients with metastatic renal cell carcinoma after unsuccessful first-line sunitinib treatment. The comparison was sorafenib alone versus sorafenib with low-dose interferon alpha-2a.

Progression-free survival was the primary outcome, with tumor assessment scheduled every 8 weeks and a stated timeframe extending from the first subject’s treatment start until 14 months later. The registry says efficacy analysis was not performed due to low accrual. No efficacy estimate is reported, and analyses of the listed secondary outcomes are not reported.

For safety, the registry lists serious adverse events affecting 5 of 10 participants at risk in the sorafenib group and 3 of 6 in the combination group. Other adverse events affected 9 of 10 and 5 of 6, respectively. The record does not report a reason for termination or a trial-specific sample-size justification.