Avastin and Temsirolimus Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Avastin and Temsirolimus Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma (NCT00782275), a na phase 2 study. The primary outcome is 4-month Progression-Free Survival Rate.

2. Clinical Question

3. Trial Design

This was a phase II, single-group study of bevacizumab and temsirolimus in advanced renal cell carcinoma after tyrosine kinase inhibitor failure. The registry lists enrollment of 41 and a completed status. The analysis dataset for the primary endpoint is described as all treated participants, which is not necessarily identical to the enrolled population. The number actually treated is not reported in the registry record.

The study description includes participants with histologically confirmed clear cell or non-clear cell metastatic renal cell carcinoma who had experienced progression or intolerable toxicity with a VEGF-targeted tyrosine kinase inhibitor. It allowed only 2 prior VEGF therapies. The registry does not report further eligibility details in the registry record for this analysis, so other enrollment criteria should not be inferred.

Participants received both drugs on scheduled intravenous dosing cycles. Bevacizumab was given at 10mg/kg every 2 weeks, on days 1 and 15; temsirolimus was given at 25mg weekly, on days 1, 8, 15, and 22. One cycle was 28-days. The available arm description is incomplete after the statement about bevacizumab dose changes, so additional dose-management details are not reported in the registry record.

Allocation is listed as NA, masking as NONE, and the model as SINGLE GROUP. These fields describe a nonrandomized, unmasked design with no concurrent control arm. The study description states that efficacy was to be evaluated against an historical control. The identity, endpoint estimate, and statistical comparison for that historical control are not reported in the registry record. As a result, the trial’s design can describe outcomes among treated participants, but it cannot itself provide a randomized comparison of the combination with another treatment.

The primary endpoint was the 4-month progression-free survival rate. Objective response rate and overall survival were listed as secondary outcomes. The available record indicates 3 outcome measures and 1 analysis, but does not give enough detail to establish how each outcome was analyzed or whether the listed analysis covers all outcomes. The detailed protocol, statistical analysis plan, recruitment flow, and reasons for any difference between enrollment and treated-participant counts are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis dataset is comprised of all treated participants.

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.

Population: The analysis dataset is comprised of all treated patients as opposed to enrolled patients.

6. Primary Endpoint

The registry lists the primary outcome as 4-month Progression-Free Survival Rate, measured over Disease evaluations occurred every 8 weeks (+/- 1 wk) on treatment. Relevant for this endpoint was disease status at 4 months..

The primary endpoint was the percentage of participants absent death or progression before 4 months. It is a binary outcome at a specified time: each participant’s disease status contributes to whether that participant meets the endpoint definition. The registry states that the analysis dataset comprised all treated participants. Disease evaluations occurred every 8 weeks (+/- 1 wk) on treatment, and the endpoint used disease status at 4 months.

Progression was defined using RECIST 1.0 criteria. For target lesions, progressive disease included at least a 20% increase in the sum of longest diameter, using the smallest sum recorded since treatment started as the reference, or the appearance of one or more new lesions. For non-target lesions, progression included the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.

In general, a fixed-time progression-free survival rate gives a reader a defined time point for describing the proportion of participants who have not experienced either of the specified events. It is different from a median time-to-event measure and should be interpreted according to its stated time point and event definition. A confidence interval can express uncertainty around an estimated percentage; it does not remove uncertainty or establish that the result would be the same in a different population.

The registry identifies a 90% confidence interval as the dispersion measure for this endpoint, but the numerical estimate and interval are not reported in the registry record. Consequently, the posted information does not permit assessment of the primary endpoint’s observed rate or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a fixed-time percentage represent?

The primary outcome is a percentage of participants who were absent death or progression before 4 months. In general, a binary endpoint classifies each participant according to whether a defined event or condition occurred. The percentage then describes the share of the analysis population meeting the endpoint definition. It is important to keep the denominator and event definition in view: a percentage is not meaningful without knowing who was analyzed and what counted as an event.

For this trial, the registry states that the analysis dataset comprised all treated participants. It does not report the number treated, the number included in the primary calculation, or the number who met the endpoint. Enrollment was 41, but enrolled and treated populations need not be identical. The reason for any difference between them is not reported in the registry record. The primary percentage itself is also not reported, so no estimate can be reconstructed from the other information.

How does progression enter the endpoint?

The endpoint combines death and disease progression before the stated time point. Progression was assessed using RECIST 1.0. For target lesions, the registry definition includes at least a 20% increase in the sum of longest diameter relative to the smallest sum recorded since treatment started, or one or more new lesions. For non-target lesions, the definition includes one or more new lesions and/or unequivocal progression. These rules define the clinical classification that underlies the binary outcome.

Disease evaluations were scheduled every 8 weeks (+/- 1 wk) on treatment. In general, assessment schedules matter because the recorded time of progression depends in part on when disease is evaluated. The endpoint refers to disease status at 4 months, while the registry does not describe how assessments that were missed, delayed, or unavailable were handled. That handling is not reported in the registry record and should not be assumed.

What does a confidence interval add?

The registry specifies a 90% confidence interval as the measure of dispersion for the primary percentage. In general, a confidence interval conveys statistical uncertainty around an estimated quantity. A narrower interval indicates greater precision under the method’s assumptions, while a wider interval indicates less precision. The interval is not a probability statement that an individual participant will have a particular outcome, and it does not address every possible source of bias.

The numerical interval endpoints are not reported in the registry record. Without the estimate and interval, neither the magnitude of the primary result nor its statistical precision can be evaluated. The confidence level alone is not a result. The interval method, any adjustment, and any treatment of participants with incomplete endpoint status are also not reported in the registry record.

Why does the design affect statistical interpretation?

The registry describes a single-group, unmasked phase II trial. In general, an estimate from one group can describe outcomes in the observed analysis population, but a treatment effect is a comparison between outcomes under different treatment conditions. A concurrent randomized group helps provide a basis for that comparison. Here, no such group is listed. The study’s stated intention to evaluate the regimen against an historical control does not, by itself, identify the external comparison data or explain how comparability was addressed.

Without random allocation and a concurrent comparator, observed outcomes can be influenced by participant selection, disease characteristics, follow-up practices, and other differences between the study group and any external benchmark. This is a general design limitation, not a claim that any particular bias occurred in this trial. The registry does not report a specific historical-control estimate or its analysis, so a comparative effect cannot be assessed from the posted record.

What do planning calculations mean?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, power, allocation, and analysis method. It is not a measure of the probability that a completed trial found a true effect. The planning assumptions described for the calculations accompanying this trial use a two-sided significance level of 0.05, equal allocation between 2 arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These are planning illustrations, not the trial’s own design rationale.

The assumptions also distinguish measures reported as participants per arm from time-to-event calculations reported as a total number of events using the Schoenfeld approach. In general, translating an effect estimate into a planning illustration does not create observed evidence and does not establish that a trial had a given probability of success. No sample-size justification, targeted power, or prospective design calculation is reported in the registry record. Because the trial itself is single-group, illustrations using equal allocation between 2 arms should not be read as a description of how participants were assigned in this study.

Any planning illustration based on an observed effect depends on the quality and uncertainty of that observed estimate. In this case, the primary endpoint estimate is not reported in the registry record, so the reader cannot independently evaluate the basis of such an illustration from the posted primary result. The registry’s stated assumptions should therefore be understood as assumptions for planning, not as evidence about treatment performance or the trial’s design.

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("Bevacizumab + Temsirolimus")
n      <- c(40)
events <- c(26)
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  Bevacizumab + Temsirolimus  40  26  65.0  48.3  79.4  49.5  77.9  49.4  77.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary endpoint as 4-month progression-free survival rate and lists objective response rate and overall survival as secondary outcomes. It also records 3 outcome measures and 1 analysis. These details identify several outcomes of interest, but they do not describe an outcome hierarchy, a family of hypotheses, or a procedure for controlling the chance of false-positive findings when multiple outcomes are tested. Any multiplicity strategy is not reported in the registry record.

In general, multiplicity matters when several outcomes or analyses are interpreted as confirmatory. Testing multiple hypotheses can increase the chance that at least one result appears notable by chance. A prespecified hierarchy, adjustment, or clearly exploratory framing can help readers understand how to interpret multiple results. The presence of secondary outcomes alone does not show which approach was used in this trial.

The primary analysis population is described as all treated participants. The registry does not report a detailed method for missing endpoint status, missed disease evaluations, withdrawal, or follow-up after treatment discontinuation. It also does not state whether any sensitivity analyses were used to examine missing data. These procedures are not reported in the registry record; no particular imputation or censoring method should be assumed.

In general, missing data can affect a percentage if participants without an observed status are excluded, classified as events, or handled by another method. Different approaches can lead to different interpretations, especially when missingness is related to health status or treatment experience. Without the missing-data rules and participant flow, the completeness and sensitivity of the primary analysis cannot be evaluated.

The registry does not provide a full statistical analysis plan, a protocol-based sample-size justification, or details of interim analyses. Those items are not reported in the registry record. Their absence from the listed information does not establish that a particular procedure was or was not used; it means the posted record does not document it.

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: hypertriglyceridemia (15.0%), hypertension (12.5%), fatigue (10.0%), hypophosphatemia (10.0%), proteinuria (10.0%).

The safety listing gives 40 participants at risk for serious adverse events and 28 affected. For other adverse events, it gives 40 at risk and 38 affected. These counts describe the recorded safety groups; they should not be treated as efficacy outcomes or as a comparison between separate treatment arms. The registry lists one combination group, Bevacizumab + Temsirolimus.

The listed serious adverse event terms include Hypertriglyceridemia at 15.0%, Hypertension at 12.5%, Fatigue at 10.0%, Hypophosphatemia at 10.0%, Proteinuria at 10.0%, and Nausea at 7.5%. These are the most frequent serious terms identified in the record, not an exhaustive description of every possible adverse event. The registry’s serious-event listing does not establish that any event was caused by treatment.

In general, a participant count at risk is the denominator for interpreting the corresponding affected count. The enrollment count is 41, while the safety listings give 40 at risk. The reason for this difference is not reported in the registry record. The deaths field is null, so death counts are not reported in the registry record. Duration of safety follow-up, event definitions beyond the serious/other categories, and details of event attribution are not reported in the registry record.

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

The study record describes a phase II evaluation of bevacizumab plus temsirolimus in participants with metastatic renal cell carcinoma after progression or intolerable toxicity with a VEGF-targeted tyrosine kinase inhibitor. The primary endpoint was a 4-month progression-free survival rate among treated participants, defined by absence of death or progression before 4 months. These design and endpoint details clarify the question the study set out to address.

The central numerical primary result is not reported in the registry record. The 90% confidence interval is named as the dispersion measure, but its endpoints are also not reported. As a result, the posted information does not show the observed 4-month rate or how precisely it was estimated. The listed secondary outcomes are objective response rate and overall survival, but numerical results for them are not reported in the registry record either.

The single-group design permits a description of outcomes in the treated population if results are reported, but it does not offer a concurrent control group for a direct randomized comparison. The study description refers to evaluation against an historical control; the specific historical data and comparison are not reported in the registry record. In general, external comparisons can be affected by differences in populations, measurement, and care, so the reference and analytic approach matter.

These limitations do not mean that the combination did or did not produce a particular outcome. They mean that the posted record does not contain the primary numerical evidence needed to characterize the observed rate, its uncertainty, or a comparative effect. No treatment conclusion should be drawn from the study title, dosing schedule, enrollment count, or stated objective alone.

14. Why This Trial Matters Statistically

This trial is statistically notable as a single-group phase II study with a fixed-time binary primary endpoint. The design makes the main estimand a proportion of treated participants meeting a defined status at 4 months, rather than a randomized contrast between two assigned groups. Recognizing that distinction helps prevent a descriptive rate from being interpreted as a comparative treatment effect.

The endpoint definition also illustrates why outcome construction matters. It combines death and progression, and progression relies on RECIST 1.0 criteria for target and non-target lesions. Assessment timing was every 8 weeks (+/- 1 wk), while the endpoint refers to 4-month disease status. In general, both the event rules and assessment schedule shape what the resulting percentage represents.

The record’s intended historical-control context raises a further statistical issue: an external comparison requires enough detail to judge whether the groups and outcome ascertainment are comparable. The registry record does not report the historical-control estimate or the method used to compare it. Thus the design should be distinguished from a randomized controlled comparison.

Finally, the registry identifies a 90% confidence interval but does not report its numerical endpoints or the primary rate. This highlights the difference between naming a statistical method and reporting a result that readers can evaluate. The design and endpoint can be understood, but the outcome’s magnitude and precision cannot be assessed from the posted registry information.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary endpoint estimate and its 90% confidence interval are not reported in the registry record. This prevents assessment of the observed 4-month progression-free survival rate, its precision, or how it compares with any benchmark. The study description refers to an historical control, but its data and comparison method are not reported in the registry record.

The single-group design has no concurrent control arm, and masking is listed as NONE. In general, a lack of randomization and concurrent comparison limits causal interpretation and leaves outcome assessment open to influences other than treatment. This is a design consideration; it does not establish that bias occurred.

Enrollment was 41, whereas the safety listings identify 40 participants at risk. The reason for the difference is not reported in the registry record. The primary analysis is described as all treated participants, but the treated count, participant flow, and number included in the endpoint calculation are not reported. Missing endpoint status and its handling are also not reported in the registry record.

The registry lists objective response rate and overall survival as secondary outcomes, but their numerical results and detailed analyses are not reported. It also does not report a multiplicity strategy, interim analysis details, a full statistical analysis plan, or a protocol-based sample-size justification. The available description of the intervention is truncated during the dosing-management text, so further dose modification rules are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Avastin and Temsirolimus Following Tyrosine Kinase Inhibitor Failure in Patients With Advanced Renal Cell Carcinoma — NCT00782275.
• Registry record last updated 2018-01-24; status last verified 2018-01.
• Results first posted 2017-12-20.
• 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

NCT00782275 is a completed phase II, single-group trial of bevacizumab plus temsirolimus following tyrosine kinase inhibitor failure in advanced renal cell carcinoma. Enrollment was 41. The primary endpoint was the 4-month progression-free survival rate among treated participants, with progression defined using RECIST 1.0. The registry specifies a 90% confidence interval but does not report the numerical primary result or interval.

Objective response rate and overall survival were listed as secondary outcomes. The registry describes an intention to evaluate efficacy against an historical control, but does not report the historical comparison. Safety listings give 40 participants at risk in the combination group, with 28 affected by serious adverse events and 38 affected by other adverse events. The reason the safety denominator differs from enrollment is not reported in the registry record.