This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Sorafenib in Treating Patients Who Are Undergoing Surgery for Metastatic Kidney Cancer (NCT00126659), a non-randomized phase 2 study. The primary outcome is Efficacy of BAY 43-9006 by Evaluating Response Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00126659 |
| Phase | Phase 2 |
| Condition | Clear Cell Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage IV Renal Cell Cancer |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
Patients with metastatic renal cell carcinoma undergoing surgery; the conditions listed include clear cell, recurrent, and stage IV renal cell cancer. The registry record reports enrollment of 10 and states that response could not be assessed because of the small sample size.
Intervention
Sorafenib tosylate given orally around cytoreductive nephrectomy, with the timing of surgery and sorafenib differing across three groups. The registry also lists therapeutic conventional surgery and laboratory biomarker analysis.
Comparator
The registry record describes three non-randomized groups with different treatment sequences. It does not identify a randomized control group, and these groups should not be treated as a like-for-like comparison.
Primary question
How was response to the neoadjuvant sorafenib strategy evaluated in patients with metastatic renal cell carcinoma undergoing nephrectomy? The primary endpoint was response rate using RECIST criteria; an assessable response result is not reported in the registry record.
The trial addressed the timing of sorafenib in relation to cytoreductive nephrectomy. One group underwent surgery before beginning sorafenib; two groups received sorafenib before surgery, with surgery scheduled at different points in their treatment sequence. The registry descriptions also state that patients with stable or regressing disease could continue sorafenib, subject to disease progression or unacceptable toxicity. These schedules make the study a comparison of treatment sequences in a small, non-randomized phase II study, not a randomized test of sorafenib against an untreated control.
The clinical question is therefore descriptive and exploratory: whether response could be evaluated under these perioperative treatment schedules. The registry record says response was unable to be assessed due to small sample size. It does not report a response count, response rate, or comparative estimate. The study record can clarify the intended endpoint and treatment structure, but it cannot establish an observed response frequency from the information reported.
3. Trial Design
This was a phase II, non-randomized, parallel-group study sponsored by the National Cancer Institute. The registry lists enrollment of 10 and no masking. The study is marked terminated. Its start is recorded as 2006-01, and primary completion is recorded as 2009-12. The registry does not report why the trial was terminated.
Three groups followed distinct sequences. Group I underwent cytoreductive nephrectomy on day 1 and then received oral sorafenib twice daily on days 15-84. Group II received oral sorafenib twice daily on days 1-7, underwent nephrectomy on day 8, and then received sorafenib on days 22-84. Group III received sorafenib twice daily on days 1-28, underwent nephrectomy on day 29, and then received sorafenib on days 43-84. The record states that patients with stable or regressing disease could continue sorafenib for up to 1 year, subject to progression or unacceptable toxicity. The continuation description is truncated in the record.
Because allocation was non-randomized, differences among the groups cannot be interpreted as if treatment timing had been randomly assigned. The registry specifically notes that the arms are not a like-for-like control comparison. It does not report the allocation process, the number of participants assigned to each group, or baseline characteristics by group. It also does not report a planned statistical analysis in the posted results; the count of analyses is 0. The record does not state a sample-size justification, interim analysis plan, or detailed statistical analysis plan.
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: This trial was run at the same time as a competing trial and suffered from poor accrual. For that reason it was closed.
Overall Study
| Stage | Cytoreductive Nephrectomy Day 0 | Sorafenib + Cytoreductive Nephrectomy Day 8 | Sorafenib + Cytoreductive Nephrectomy Day 29 |
|---|---|---|---|
| STARTED | 3 | 3 | 4 |
| COMPLETED | 3 | 3 | 2 |
| NOT COMPLETED | 0 | 0 | 2 |
Reasons for not completing this period:
| Reason | Cytoreductive Nephrectomy Day 0 | Sorafenib + Cytoreductive Nephrectomy Day 8 | Sorafenib + Cytoreductive Nephrectomy Day 29 |
|---|---|---|---|
| Adverse Event | 0 | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: Unable to assess response due to small sample size.
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.
| Characteristic | Unit | Cytoreductive Nephrectomy Day 0 | Sorafenib + Cytoreductive Nephrectomy Day 8 | Sorafenib + Cytoreductive Nephrectomy Day 29 | Total |
|---|---|---|---|---|---|
| Participants analysed | 3 | 3 | 4 | 10 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 1 | 2 | 4 |
| Age, Categorical: >=65 years | Participants | 2 | 2 | 2 | 6 |
| Sex: Female, Male: Female | Participants | 3 | 1 | 1 | 5 |
| Sex: Female, Male: Male | Participants | 0 | 2 | 3 | 5 |
| Region of Enrollment: United States | participants | 3 | 3 | 4 | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Efficacy of BAY 43-9006 by Evaluating Response Rate, measured over Every 2 weeks during 4 week cycle.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was response rate, defined as participants with response divided by the total number of participants. Response was to be evaluated using criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The stated timeframe was every 2 weeks during a 4 week cycle.
Under the recorded criteria, complete response means disappearance of all target lesions. Partial response requires a > 30% decrease in the sum of the longest diameters of target lesions, relative to the baseline sum. Progressive disease is a > 20% increase in the sum, relative to the smallest sum recorded since treatment started, or the appearance of 1 or > new lesions. Stable disease means neither enough shrinkage to qualify as partial response nor enough increase to qualify as progressive disease, using the smallest sum since treatment started as the reference.
Response rate is used to describe the proportion of participants meeting a response definition over the assessment period. It translates lesion measurements into clinically interpretable response categories, although the endpoint alone does not describe the full course of disease or establish a causal treatment effect. The registry record says response could not be assessed because of the small sample size. It does not report a response count, response rate, or uncertainty interval.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary endpoint is described, but the registry record does not report an assessable response result. Its population statement says response was unable to be assessed due to small sample size. Consequently, no response frequency or treatment contrast can be interpreted from the posted results. This is different from a reported response rate of zero: absence of an assessable result does not establish that no participant responded.
The registry reports enrollment of 10, but does not provide participant flow, the number assessed for response, or the number assigned to each of the three groups. Enrollment should not be assumed to equal the analysis population. The record also does not provide group-level response data, baseline disease measures, or follow-up completeness. Without those details, it is not possible to assess how the endpoint was applied in practice or whether assessment differed among treatment sequences.
The trial was non-randomized. Its three groups varied in the timing of sorafenib and surgery, and the registry cautions that the arms are not a like-for-like control comparison. Any apparent difference between groups, if one were reported elsewhere, would need to be interpreted in light of possible differences in who entered each group and other factors associated with treatment sequence. The registry record reports no comparative analysis, and it does not provide an adjusted estimate.
No confidence interval, test statistic, or p-value for response is reported in the registry record. General: a confidence interval describes the range of estimates compatible with the data under a specified method and communicates precision; a statistical test addresses compatibility with a null hypothesis under its assumptions. Neither can be interpreted when the underlying endpoint estimate and analysis are absent. A small study can yield imprecise estimates, but the registry does not supply enough response information to quantify that imprecision.
The record lists 10 participants at risk for adverse-event reporting, 1 affected by a serious adverse event, and 10 affected by other adverse events. These safety counts describe the recorded group, not a comparative safety effect. The serious adverse event term listed among the leading terms is hyperuricemia at 10.0%. No causal conclusion follows from these descriptive entries alone.
Planning illustrations based on an observed effect, if displayed with the posted results, are not observed power and are not the trial's original design justification. The assumptions describe two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with effects expressed as fractions of the observed effect. The registry record does not report an assessable response effect from which to interpret such illustrations. They should not be read as evidence about the trial's achieved power or its results.
9. Statistical Methods Explained
The registry describes the study as phase II, non-randomized, parallel, and unmasked. Those design labels set limits on the conclusions that can be drawn. The three groups received different sequences of sorafenib and surgery, but participants were not randomly allocated according to the record. The design therefore does not create the same basis for a causal comparison that random allocation can provide. The registry explicitly cautions that the arms are not like-for-like controls.
What does response rate measure?
Response rate is a categorical endpoint: each participant is classified according to whether their tumor measurements meet the criteria for response, and the endpoint is the number with response relative to the total number of participants. The registry specifies RECIST-based categories and regular assessment timing. Complete and partial response reflect defined levels of lesion change; progressive disease reflects a specified increase or new lesions; stable disease is the category that meets neither the response nor progression thresholds. Such criteria aim to make assessment systematic rather than dependent on an informal judgment.
General: turning continuous measurements into categories can make results easier to communicate, but it also discards some information about the size and trajectory of change. The classification depends on the measurement rules, baseline reference, assessment schedule, and availability of evaluable scans. The registry does not report scan-level data, how missing assessments were handled, or whether response assessments were independently reviewed.
Why does allocation matter?
Random allocation is a method for balancing known and unknown participant characteristics across groups on average. In a non-randomized study, group differences can reflect both treatment sequence and characteristics related to how participants entered or remained in a group. Here, surgery and sorafenib timing varied across the groups, so a between-group difference would not by itself isolate the effect of one schedule. No randomized comparator is reported, and the record warns against treating the groups as equivalent controls.
General: adjustment for measured baseline differences can sometimes reduce confounding, but it cannot guarantee removal of bias from unmeasured factors. The posted results list no analyses, and the registry record does not report an adjustment method or a model. There is therefore no adjusted treatment estimate to interpret.
What can uncertainty estimates add?
General: an estimate such as a response proportion is only a point summary. A confidence interval communicates how much uncertainty remains around that estimate under the chosen statistical procedure. The width depends on the amount of information and the analysis assumptions. A hypothesis test may also be reported, but its p-value is not a measure of effect size or clinical importance.
The registry record does not report a response proportion, confidence interval, or p-value. With no reported response analysis, precision cannot be quantified, and no claim about statistical significance can be made. The registry statement that response could not be assessed due to small sample size is the only reported description of the primary endpoint's assessability.
What do the planning assumptions mean?
The planning description refers to illustrations computed from an observed effect, rather than the trial's own design. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. For time-to-event settings, the description refers to a total number of events; for other settings, it refers to participants per arm for 80% power or other stated power levels.
General: a planning calculation estimates the sample size that would be required under chosen assumptions; it does not show the power actually achieved after a study is complete. It is also not evidence that the study was designed using those assumptions. Since the registry record provides no assessable response effect or reported response analysis, these assumptions cannot supply a result for the primary endpoint. Any displayed planning values should be understood as illustrations and not as observed power.
What does the registry's analysis count indicate?
The posted record lists 0 analyses. This means no analysis entries are reported in the registry record; it does not establish that no analyses were conducted outside the registry. No statistical model, covariate adjustment, missing-data method, or multiplicity procedure is reported. The methods available for interpretation are therefore limited to the stated endpoint definition, assessment timeframe, design labels, and descriptive safety entries.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint is response rate, but the registry record does not report an analysis result for it. Although the record lists 4 outcome measures, it does not describe how the primary endpoint was prioritized in any formal testing strategy, how secondary outcomes were handled, or whether any adjustment for multiple comparisons was planned. A multiplicity plan is not reported in the registry record. Without reported tests or estimates, there is no basis for assessing whether a particular significance threshold was applied across outcomes.
Missing-data handling is also not reported in the registry record. The record does not state how participants without evaluable imaging, missed assessments, withdrawals, or incomplete follow-up were treated in the response analysis. It does not report whether response was assessed in all enrolled participants or in a defined subset. The statement that response could not be assessed because of small sample size does not identify the specific reason assessments were unavailable or how the endpoint was handled analytically.
Analysis populations are not described. The record does not report an intention-to-treat population, a per-protocol population, or a safety population definition. Enrollment of 10 cannot by itself show how many participants contributed to each outcome. The record also does not report group-specific participant counts or exclusions. The count of 0 analyses indicates that analyses are not listed in the registry record, rather than providing details about which participants were included in a particular model or endpoint calculation.
General: multiplicity matters when several endpoints, comparisons, or repeated tests are evaluated, because the chance of at least one false-positive finding can rise without an appropriate strategy. Missing-data methods matter because the observed participants may differ from those whose outcomes are unavailable. These are general statistical concerns; the registry does not provide enough detail to determine whether or how they affected this trial.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Sorafenib + Cytoreductive Nephrectomy | 1 | 10 | 10.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sorafenib + Cytoreductive Nephrectomy | 10 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Sorafenib + Cytoreductive Nephrectomy |
|---|---|---|
| hyperuricemia | Blood and lymphatic system disorders | 1 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sorafenib + Cytoreductive Nephrectomy |
|---|---|---|
| fatigue | General disorders | 10 of 10 |
| diarrhea | Gastrointestinal disorders | 4 of 10 |
| hemoglobin | Blood and lymphatic system disorders | 4 of 10 |
| hypomagnesemia | Blood and lymphatic system disorders | 4 of 10 |
| mucositis | General disorders | 4 of 10 |
| rash/desquamation | Skin and subcutaneous tissue disorders | 4 of 10 |
| nausea | Gastrointestinal disorders | 3 of 10 |
| platelets | Blood and lymphatic system disorders | 3 of 10 |
| alopecia | General disorders | 2 of 10 |
| hypertension | Blood and lymphatic system disorders | 2 of 10 |
Serious events with the highest arm-level rate: hyperuricemia (10.0%).
The registry lists a combined group titled Sorafenib + Cytoreductive Nephrectomy. For that group, 10 participants were at risk for serious adverse events and 1 was affected. For other adverse events, 10 were at risk and 10 were affected. Hyperuricemia is listed among the leading serious adverse event terms at 10.0%. The registry does not provide a full event-by-event account in these entries.
These are descriptive safety figures. They do not establish that sorafenib or surgery caused an event, and the entries do not provide a comparison with a control group. The group combines treatment and surgery, so the counts do not separate events by treatment sequence or identify which component may be related to an event. The record does not report event timing, severity grades beyond the serious classification, or participant-level details.
The deaths entry is not reported in the registry record. That should not be interpreted as a count of zero deaths. General: adverse-event counts depend on how events are defined, collected, and attributed. The available entries give a limited account of events among those at risk, not a complete safety profile or a comparative estimate.
12. What the Result Does, and Does Not, Mean
The registry record documents a phase II study of sorafenib given in different sequences around cytoreductive nephrectomy for metastatic renal cell carcinoma. It specifies a RECIST-based response-rate endpoint and states that response was unable to be assessed due to small sample size. The record does not report a response count, response rate, or comparative effect. The central statistical conclusion is therefore that the primary endpoint result cannot be evaluated from the registry entries.
This absence of a reported result is not evidence that the response rate was zero, that treatment had no effect, or that the treatment had an effect. It means the registry record does not provide an assessable endpoint result. Nor does it establish that no analysis was done outside the registry; it reports 0 analyses in the posted results.
The three groups followed different treatment schedules, but allocation was non-randomized. The registry cautions that the groups are not like-for-like control comparisons. Accordingly, the design does not support interpreting a difference between groups as a causal effect of a particular timing schedule. Enrollment was 10, and the registry does not report group sizes, participant flow, response-assessment completeness, or baseline comparisons.
The safety entries report serious adverse events in 1 participant among 10 at risk and other adverse events in 10 among 10 at risk. Hyperuricemia is listed at 10.0% among the leading serious event terms. These entries are descriptive and do not establish causation or comparative safety. The deaths entry is not reported in the registry record.
Planning illustrations based on an observed effect, when considered, should be kept separate from trial outcomes. They do not represent observed power and do not replace the missing response analysis. In statistical terms, the record supports a description of study design, endpoint criteria, and limited safety counts, but not an estimate of response or a precise treatment effect.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its endpoint is clearly defined while its result is not assessable in the registry record. The response criteria specify how tumor measurements were to be categorized, but a formal definition alone cannot provide evidence about the observed response experience. For interpretation, the number of participants with an assessable outcome and the result itself are essential.
The study also highlights the limits of non-randomized, multi-group comparisons. The groups differed in when sorafenib was given relative to surgery, so group membership may reflect more than the treatment schedule. The registry itself cautions that the arms are not like-for-like controls. A statistical comparison, even if available, would need to be read in light of the design and any differences in participant characteristics; the posted results do not report such an analysis.
The small enrollment and the statement that response could not be assessed draw attention to the distinction between planning and evidence. Sample-size illustrations based on an observed effect are planning calculations, not observed power and not proof that the original design was adequate. The registry does not report a sample-size justification, so those planning illustrations should not be confused with the study's stated design rationale.
Finally, the record shows why missing analysis details matter. It does not report participant flow, analysis populations, missing-data handling, multiplicity procedures, or inferential estimates. Without those details, readers cannot judge the precision of response estimates or reconstruct a comparative analysis. The statistically responsible reading is bounded: the design and endpoint are documented, but the primary response result is unavailable for interpretation in the registry record.
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 key limitation is that the primary response endpoint is not assessable in the registry record. The record does not provide response counts, a response rate, or an uncertainty interval. It attributes the inability to assess response to small sample size, but does not explain whether the limitation arose from enrollment, evaluable assessments, follow-up, or another factor.
Enrollment is reported as 10, with no group-specific counts or participant flow. It is not possible to determine how many participants entered each schedule, completed surgery, received sorafenib, or contributed to response assessment. The registry does not report baseline characteristics by group, which further limits interpretation of any possible differences between treatment sequences.
Non-randomized allocation and the absence of a like-for-like control comparison limit causal interpretation. The groups vary in the timing of surgery and sorafenib, and the record does not report adjustment for differences among participants. The registry also does not report the statistical analysis plan, sample-size justification, interim analyses, missing-data methods, analysis populations, or multiplicity procedures.
The safety record is limited to aggregate counts and a listed serious adverse event term. Event-level detail, timing, attribution, and deaths are not reported in the registry record. The trial is marked terminated, but the reason for termination is not reported. These limitations mean the record is useful for understanding the intended study structure, but it does not support a complete assessment of efficacy, comparative safety, or precision.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Sorafenib in Treating Patients Who Are Undergoing Surgery for Metastatic Kidney Cancer — NCT00126659.
- Registry record last updated 2018-11-20; status last verified 2018-10.
- Results first posted 2012-12-31.
- 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.
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18. Record Summary
The registry describes a phase II, non-randomized, parallel study of sorafenib around cytoreductive nephrectomy in metastatic renal cell carcinoma. Enrollment was 10. Three groups followed different treatment sequences, and the study is marked terminated. The primary endpoint was RECIST-based response rate, assessed every 2 weeks during a 4 week cycle.
The registry record states that response could not be assessed due to small sample size. It reports 0 analyses and provides no response count, response rate, or comparative estimate. Safety entries list 1 serious adverse event among 10 at risk and other adverse events in 10 among 10 at risk; hyperuricemia is listed at 10.0% among the leading serious terms. Deaths are not reported in the registry record. The non-randomized groups are not like-for-like controls, so the posted information supports a limited descriptive account rather than a causal treatment comparison.