Vandetanib to Treat Advanced Kidney Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vandetanib to Treat Advanced Kidney Cancer (NCT01372813), a na phase 2 study. The primary outcome is Number of Participants With a Clinical Response (Partial Response (PR) + Clinical Response (CR)).

2. Clinical Question

3. Trial Design

This was a phase II study of vandetanib in advanced clear cell renal carcinoma. The registry identifies the design as single group, allocation as not applicable, and masking as none. Enrollment was 3. The National Cancer Institute sponsored the study. Its registry status is terminated; the recorded start is 2007-12 and primary completion is 2010-06. The reason for termination is not reported in the registry record.

The intervention description specifies a vandetanib pill once a day in 28-day cycles. The study summary describes clinic visits every 2 weeks during the first month, followed by visits every 4 weeks. These visits included a physical examination, blood and urine tests, an electrocardiogram, and review of drug side effects. Imaging with CT or MRI was planned about every 8 weeks to monitor tumor growth. The summary is truncated during a further description of MRI procedures, so additional imaging details are not reported in the registry record.

The population was described as adults with advanced clear cell kidney cancer meeting the treatment-history or treatment-ineligibility criteria. Because there is no separate comparison group, the design can describe outcomes among participants in the study but cannot directly distinguish treatment effects from other explanations for changes over time. No randomized allocation or masking is recorded.

The stated objectives also included examining how vandetanib may work in people with kidney cancer and developing tests for studying the disease. Secondary outcomes covered plasma biomarkers, circulating endothelial progenitor and endothelial cells, progression-free survival under RECIST, adverse events, dynamic contrast-enhanced MRI assessments of tumor vascular flow and permeability, tumor tissue assessments of VHL status and pathway components, and tumor microvessel density. Results for these secondary outcomes 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

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 Participants With a Clinical Response (Partial Response (PR) + Clinical Response (CR)), measured over 12 months.

The primary endpoint counted participants whose best recorded clinical response was a partial response or complete response. The registry defines response using RECIST and considers the best response from treatment start until disease progression. The stated timeframe is 12 months.

For a partial response, the registry definition requires at least a 30% decrease in the sum of the longest diameter of target lesions, using the baseline sum as the reference. A complete response means disappearance of all target lesions. Combining these categories into a clinical-response count gives a binary outcome at the participant level: a participant either meets the response definition or does not.

This kind of endpoint is used to describe whether measurable tumor lesions shrink enough to meet a prespecified response criterion. It is not the same as measuring how long a response lasts, how long participants live, or whether symptoms improve. The endpoint also does not by itself establish that a change was caused by the study treatment, particularly in a single-group design without a comparator.

The registry record does not report the number of participants meeting the endpoint, a response proportion, or an uncertainty interval. Therefore, the endpoint definition can be described, but the observed clinical-response result and its precision cannot be evaluated from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a participant-level binary endpoint: clinical response is counted when the best response is partial response or complete response under the stated RECIST definitions. For a binary outcome, a basic descriptive result is the number meeting the definition and the number assessed. A proportion can then describe the observed frequency in the study group. Here, the registry record does not report the response count or the number assessed for the primary endpoint, so neither the count nor a proportion can be evaluated.

A confidence interval is a statistical range expressing uncertainty around an estimate under a specified method. For a response proportion, it would convey how much uncertainty remains because the result is based on a limited group of participants. It does not guarantee that the true value lies within a particular interval, and it does not address design limitations such as the lack of a comparator. No confidence interval for clinical response is reported in the registry record.

A single-group study has no randomized control arm against which to estimate a treatment contrast. This means its results, if reported, would be descriptive of the study participants and would not by themselves isolate the intervention’s effect from other possible explanations. Randomization in a comparative study can help balance measured and unmeasured factors across groups; there is no randomized allocation recorded for this study. The registry lists masking as none.

The registry’s sample-size assumptions describe a planning illustration, not the study’s own design or an observed power calculation. The illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. The trial itself is recorded as a single-group study, so those two-arm assumptions should not be mistaken for its actual allocation. For outcomes other than time-to-event outcomes, the planning figures are described as participants per arm. For time-to-event outcomes, the description refers to the total number of events using the Schoenfeld approach. The registry record does not report the observed effect or the resulting planning figures, so no sample-size value can be interpreted from the record.

Planning sample sizes answer a hypothetical question about how many participants might be needed under specified assumptions to detect a chosen effect with a specified statistical framework. They are not observed study outcomes, and they are not evidence that the study had a particular probability of detecting an effect. In general, such calculations depend on assumptions about the outcome, effect size, significance level, allocation, and analysis method. If those assumptions differ from what occurs in a study, the calculation may not describe the study’s actual operating characteristics. The registry record does not report the protocol’s sample-size justification or statistical plan.

Multiplicity arises when investigators examine several outcomes or make several statistical comparisons. In general, the more hypotheses examined, the more opportunity there is for a nominally unusual result to occur by chance. Approaches to multiplicity may define one primary hypothesis, adjust significance thresholds, or interpret secondary results as exploratory. The registry lists multiple secondary outcomes, but any multiplicity strategy is not reported in the registry record. There are no analysis results listed from which to assess how multiple outcomes were handled.

Missing-data methods matter when participants do not have an observed result for an endpoint or leave follow-up before assessment. The registry record does not describe missing primary outcome data, the number assessed for response, or any approach for handling missing results. Therefore it is not possible to determine whether the primary endpoint was evaluated for all enrolled participants or whether any assumptions were used for unobserved outcomes.

Analysis populations also affect interpretation. A protocol may define which participants are included in an endpoint analysis, such as those enrolled, treated, or evaluable under specific criteria. The analysis population for the primary endpoint is not reported in the registry record. The available information does not establish who was included in any efficacy analysis.

These methodological concepts explain what would be needed to interpret a response estimate, but they do not fill in the absent result. The primary response count, precision estimate, analysis population, handling of missing data, and statistical analysis are not reported in the registry record.

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("Clear Cell Renal Carcinoma Patients")
n      <- c(3)
events <- c(0)
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  Clear Cell Renal Carcinoma Patients  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary clinical-response endpoint and multiple secondary outcomes. The secondary topics include biomarkers, circulating endothelial cells and progenitor cells, progression-free survival, adverse events, imaging assessments, tumor tissue assessments, and microvessel density. When a study considers several outcomes, multiplicity is relevant because repeated testing can increase the chance of at least one apparently notable result. In general, a statistical plan may designate a primary analysis and specify how secondary analyses will be interpreted or adjusted. The multiplicity strategy is not reported in the registry record.

The registry record lists no analyses. It does not report a statistical analysis plan, hypothesis-testing approach, confidence intervals, or model specifications. No conclusion about whether analyses were prespecified or adjusted for multiple outcomes can be drawn from the posted results.

Missing-data handling is also not reported in the registry record. The record does not give the number of participants assessed for the primary response endpoint, describe missing response assessments, or state how any unavailable outcomes were handled. Without those details, it is not possible to assess whether the reported analysis population—if any—would match all enrolled participants.

The analysis population for the primary and secondary outcomes is not reported in the registry record. Neither intention-to-treat nor evaluable-participant definitions are stated. Consequently, the enrollment figure alone cannot establish which participants contributed to an endpoint analysis. These omissions limit assessment of the analysis process, independently of the absence of outcome estimates.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhea (33.3%).

The registry safety entry is for the group titled Clear Cell Renal Carcinoma Patients. It lists 3 participants at risk for serious adverse events and 1 participant affected. For the other adverse-event category, it lists 3 at risk and 3 affected. These are registry counts; they do not by themselves establish that the study intervention caused an event.

The registry also lists diarrhea among the top serious adverse-event terms, with 33.3%. That figure should be read as the registry’s reported percentage for the listed term, not as a complete description of all safety outcomes. The record does not provide event timing, severity details beyond the serious-event classification, or individual-level context for this term.

Serious adverse events and other adverse events are separate registry categories and should not be treated as interchangeable. The affected-participant counts are not a measure of treatment benefit, and they cannot be compared with efficacy in the absence of the primary response result. The registry record does not report the safety analysis methods, attribution assessments, or a comparator-group safety profile.

Because enrollment was 3, safety counts describe a very small study group. In general, such counts give limited information about the range or frequency of less common harms. The registry entry is a report of recorded adverse-event categories and should not be interpreted as proving that an event was caused by vandetanib or that unlisted events did not occur.

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

The study’s stated primary question was whether participants with advanced clear cell renal carcinoma had a clinical response, defined as partial response plus complete response under RECIST, during the stated 12 months. The registry record describes how that outcome was defined, but does not report the response count or any corresponding estimate. The posted results therefore do not establish how often clinical response occurred in the study.

The record does establish that this was a phase II, single-group study of vandetanib, with enrollment of 3 and no separate comparator group. That design can be used to describe outcomes among participants in the study, but without a comparison group it cannot directly estimate a randomized treatment contrast. The absence of reported efficacy results makes even a descriptive account of the primary endpoint unavailable.

The record also does not report statistical analyses, uncertainty intervals, or secondary outcome results. Thus, it is not possible to assess the precision of an efficacy estimate, whether the observed result—if any—was compatible with a range of effects, or how the listed secondary outcomes behaved. The status of terminated does not explain the reason for stopping, and no reason is reported in the registry record.

The safety entry reports serious and other adverse-event counts and lists diarrhea at 33.3% among the top serious terms. These entries describe what is recorded in the registry; they do not establish causation or provide a comprehensive assessment of safety. The small enrollment also limits the amount of information that can be obtained about less common outcomes.

In general, an endpoint definition, study design, and outcome estimate answer different questions. The definition specifies what was to be measured; the design determines what comparisons are supported; and the observed estimate and its uncertainty describe the result. In this record, the definition and design are available, but the primary result and its precision are not reported. Accordingly, no conclusion about treatment efficacy is supported by the posted results.

14. Why This Trial Matters Statistically

This study is a useful example of why trial design and result reporting need to be read together. The registry identifies a clinically defined population, an intervention, a single-group design, and a response endpoint based on RECIST. Those details explain what the investigators set out to examine, but they do not substitute for the observed endpoint result.

The distinction between a within-group description and a comparative treatment effect is central. A single-group study can record whether participants experienced a specified outcome, but without a comparator it cannot directly estimate how outcomes would differ under another treatment or control condition. That distinction remains important even when an endpoint is clearly defined.

The study also illustrates the role of precision. Enrollment was 3, and the registry does not report a response estimate or confidence interval. In general, estimates from very small groups are uncertain, and uncertainty should be communicated rather than inferred from a point estimate alone. Here, the absence of the endpoint result means even that descriptive estimate is unavailable.

Finally, the registry lists a broad set of secondary outcomes, spanning clinical, biological, imaging, tissue, and safety measures. Such measures can address different aspects of a research question, but their presence in a registry does not indicate that results are available or that multiplicity was addressed. Their analysis and reporting methods are not reported in the registry record. The central statistical lesson is to distinguish a planned measure from a reported result, and a reported result from evidence of a comparative effect.

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 most consequential limitation for interpretation is that the primary clinical-response result is not reported in the registry record. The record gives the endpoint definition and timeframe but does not state how many participants met the definition, how many were assessed, or how uncertain an estimate would be. The registry also lists no analyses.

The study is recorded as single group, with allocation not applicable and no masking. There is no separate randomized comparator, so the design does not support a direct treatment-versus-control estimate. The small enrollment of 3 further limits the amount of outcome information available from this study.

The registry does not report the analysis population, missing-data methods, multiplicity strategy, or statistical analysis plan. It is therefore not possible to assess which participants contributed to any endpoint analysis, how unobserved outcomes were treated, or how the several listed secondary outcomes were interpreted statistically.

The registry status is terminated, but the reason is not reported in the registry record. The study summary is truncated during its description of MRI procedures, so further procedural details are unavailable. Results for the listed secondary outcomes are also not reported in the registry record. These limitations leave both the primary efficacy question and much of the broader outcome profile unresolved.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Vandetanib to Treat Advanced Kidney Cancer — NCT01372813.
• Registry record last updated 2015-10-23; status last verified 2015-10.
• Results first posted 2012-03-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes NCT01372813, a phase II study titled Vandetanib to Treat Advanced Kidney Cancer. It was sponsored by the National Cancer Institute and studied vandetanib in advanced clear cell renal carcinoma. The study was single group, with allocation listed as not applicable, no masking, enrollment of 3, and status terminated. The recorded start was 2007-12 and primary completion was 2010-06.

The primary endpoint was the number of participants with partial or complete clinical response under RECIST, with a timeframe of 12 months. The primary result and statistical analyses are not reported in the registry record. Secondary outcomes covered progression-free survival, adverse events, biomarkers, cellular measures, imaging, tumor tissue, and microvessel density; their results are not reported in the registry record.

The safety entry lists 1 participant affected by serious adverse events among 3 at risk, and 3 affected in the other adverse-event category among 3 at risk. Diarrhea is listed among the top serious terms at 33.3%. The reason for termination and the statistical analysis plan are not reported in the registry record.