Temsirolimus and Bevacizumab in Treating Patients With Stage III or Stage IV Malignant Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Temsirolimus and Bevacizumab in Treating Patients With Stage III or Stage IV Malignant Melanoma (NCT00397982), a na phase 2 study. The primary outcome is Objective Tumor Response (Complete Response and Partial Response) and Progression in Participants With Stage III or IV Melanoma Following Treatment With Temsirolimus and Bevacizumab.

2. Clinical Question

3. Trial Design

This was a phase II study sponsored by the National Cancer Institute (NCI), registered as NCT00397982. The record lists a single treatment group and an enrollment of 17. The study started in 2008-01, reached primary completion in 2013-07, and is marked completed. Allocation was not applicable, and masking was none. There was no randomized control group.

The treatment combined temsirolimus and bevacizumab. Temsirolimus was administered intravenously over 30 minutes on days 1 and 8, with bevacizumab administered intravenously over 30–90 minutes on day 8. Courses repeated every 14 days, with treatment planned for a maximum of 26 courses in the absence of disease progression or unacceptable toxicity. Tumor resection was scheduled on day 9 of course 2. Laboratory biomarker analysis and therapeutic conventional surgery are also listed as interventions.

The registry lists six outcome measures, including adverse events, biomarker relationships, biomarker comparisons, and progression-free survival. It does not report the detailed statistical analysis plan, the basis for the enrollment target, or the procedures used to select participants for each outcome analysis. The reported enrollment therefore describes the study cohort, but the record does not establish that every enrolled participant contributed data to every outcome.

Because the study was single-group, its design can describe outcomes among participants who received the combination but cannot directly separate treatment-associated changes from other explanations. The registry record does not report a control condition or a randomized allocation process. These design features matter when interpreting both tumor outcomes and adverse-event summaries.

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:

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 Objective Tumor Response (Complete Response and Partial Response) and Progression in Participants With Stage III or IV Melanoma Following Treatment With Temsirolimus and Bevacizumab, measured over Up to 18 weeks after registration..

The primary endpoint concerns objective tumor response and progression in participants with stage III or stage IV melanoma, assessed up to 18 weeks after registration. It includes complete response and partial response, while the endpoint title also refers to progression. Tumor status was evaluated using RECIST v1.0 and assessed by MRI and/or CT.

Under the stated RECIST definitions, partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions. Stable disease means there is neither sufficient shrinkage for partial response nor sufficient increase for progression. Progression is defined by a 20% increase in the sum of the longest diameters of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. Complete response means disappearance of all target lesions.

This endpoint is used to classify tumor status according to explicit imaging criteria, rather than relying only on an informal impression of change. The registry describes the primary outcome as a number of participants. It does not report the observed counts for complete response, partial response, stable disease, or progression, nor does it explain how those categories were combined for the reported primary result. Thus, the endpoint definition is available, but its observed result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a participant count for the primary endpoint and describes RECIST-based tumor classifications. It does not report the statistical analysis methods used to turn those classifications into a primary result. The explanations below distinguish general statistical concepts from methods documented for this study.

What does a participant count convey?

In general, a count tells how many participants meet a defined event or classification. It is a direct description of the cohort, but a count alone does not convey the chance of the event unless the relevant denominator and analysis population are also clear. A proportion adds that context by relating the count to the number of participants assessed. The primary outcome is described as a number of participants, and the registry record does not provide a result count or a denominator for an outcome analysis.

General statistical practice may also report an uncertainty interval around a proportion. A confidence interval describes the range of values compatible with the data under the chosen statistical method; it is not a guarantee that the true value lies within that range. Its width depends on the amount and pattern of information and on the method used. No confidence interval for the primary outcome is reported in the registry record, so no conclusion about its numerical precision can be drawn from the endpoint definition alone.

How does RECIST define tumor status?

RECIST v1.0 applies explicit criteria to measurements of target lesions and to observations involving non-target lesions or new lesions. In this study description, imaging by MRI and/or CT was used. A partial response is defined by at least a 30% decrease in the sum of the longest diameters of target lesions. Stable disease falls between the criteria for response and progression. Progression includes a 20% increase in the target-lesion measurement, a measurable increase in a non-target lesion, or a new lesion. Complete response requires disappearance of all target lesions.

These definitions support consistent classification, but the record does not report who reviewed the images, whether review was blinded, how missing or unevaluable scans were treated, or how the primary categories were combined into a final result. Those details are not reported in the registry record. The absence of masking in the trial record describes the study’s masking status; it does not, on its own, establish the procedures used for image assessment.

What can a single-group design estimate?

In general, a single-group study can describe outcomes among people receiving the study treatment. It does not create a concurrent comparison that balances other influences between treatment groups. Without a comparator, differences from an external expectation could reflect differences in participant characteristics, assessment practices, timing, or other factors, as well as treatment. This study’s allocation is listed as not applicable and its model as single group, so no randomized treatment contrast is reported.

A randomized comparison typically estimates a contrast between groups using an outcome measure and a prespecified analysis. The registry record does not report such a contrast for this study. It also does not report a protocol-based null hypothesis, a statistical model for the primary outcome, or a decision threshold for interpreting that outcome. Those methods should not be inferred from the phase designation or endpoint definition.

How should planning calculations be read?

General sample-size calculations depend on assumptions about the effect to be detected, the significance level, allocation, and the statistical approximation. The planning illustrations associated with this study use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning assumptions, not a description of the trial’s single-group design. The record does not report that those assumptions were used to plan enrollment.

A planning sample size describes a hypothetical design under its assumptions. It is not the number of participants observed, a result of the trial, or observed power. Observed power is not a substitute for reporting an estimate and its uncertainty. The registry does not report the rationale for enrolling 17 participants, so the planning illustrations should not be treated as the investigators’ documented sample-size justification.

Why does event variability matter?

General statistical methods sometimes account for over-dispersion, meaning observed variability is greater than a simple model assumes. That issue can affect uncertainty estimates for certain count outcomes. The primary outcome is described as a number of participants, but the registry record does not report a model, dispersion assessment, or variance adjustment. It would therefore be inappropriate to claim that over-dispersion was assessed or that a particular model was used. The important distinction is between an endpoint definition, which is reported, and an analysis method, which is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary tumor-response and progression outcome and secondary outcomes involving adverse events, biomarkers, and progression-free survival. When a study examines several outcomes or several comparisons, there is a general risk that some results may appear notable by chance. A prespecified analysis plan can explain which outcomes are primary, how secondary outcomes are interpreted, and whether any adjustment for multiple testing is intended.

The registry record does not report a multiplicity strategy, such as an adjustment to account for testing multiple outcomes. It also does not report the complete statistical analysis plan, any interim analysis plan, or a hierarchy for interpreting secondary outcomes. Those items are not reported in the registry record, so the listed outcomes should not be treated as though their statistical testing procedures are known.

Missing-data handling is also not reported. The record does not explain whether all enrolled participants had endpoint imaging, how unevaluable assessments were classified, or whether participants who stopped treatment remained in the primary analysis. It does not identify an analysis population for the primary endpoint. These omissions limit interpretation because the number assessed may differ from the number enrolled, and the handling of missing assessments can affect a count or proportion.

In general, transparent outcome reporting distinguishes the enrolled cohort from the participants analyzed and describes how missing observations were handled. The registry record reports enrollment of 17 but does not give the primary outcome count or analysis population. It is consequently not possible to assess whether the endpoint result included all enrolled participants or to judge how missing data might have influenced the result.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lymphopenia (11.8%), hypophosphatemia (11.8%), hypokalemia (11.8%), weight loss (11.8%), leukoencephalopathy (5.9%).

The registry lists 17 participants at risk for serious adverse events and 9 participants affected by serious adverse events. For other adverse events, it lists 17 participants at risk and 17 affected. These are participant counts, not treatment-effect estimates. The record does not report deaths in the adverse-event group information.

The listed serious-event terms include lymphopenia, hypophosphatemia, hypokalemia, and weight loss, each reported as 11.8%, as well as leukoencephalopathy and anemia, each reported as 5.9%. These percentages are reproduced as recorded; they should not be read as measures of comparative risk because the study has no control group. The record does not provide the event-level detail needed to determine whether participants experienced more than one event or how the listed terms relate to the overall count of affected participants.

Adverse-event summaries depend on definitions, monitoring, duration of observation, and judgments about seriousness and attribution. The registry record does not give those details for these figures. In particular, a reported event among treated participants does not by itself show that the treatment caused it. The counts describe what was recorded in this study group, while the incomplete context limits comparisons and causal interpretation.

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

The registry record establishes that a phase II, single-group study enrolled 17 participants and defined a primary tumor-response and progression outcome using RECIST v1.0. It also describes the treatment schedule and provides some adverse-event counts and terms. These registry entries characterize the study and the outcomes it intended to assess.

The record does not report the primary endpoint result. There are no reported counts for complete response, partial response, stable disease, or progression, and no primary outcome estimate or confidence interval. Therefore, the posted information does not show how participants were classified or how precisely any outcome was estimated. The endpoint description is not itself evidence of a particular result.

Because there was no comparator group, the study does not provide a direct estimate of how outcomes differed from those under another treatment or a control condition. In general, observations in a single group may be influenced by participant characteristics, disease course, assessment timing, and other factors. A single-group result, even when fully reported, cannot by itself separate these influences from treatment effects.

The safety counts indicate that adverse events were recorded among participants, but they do not establish causation or comparative safety. The record does not provide enough detail to interpret event timing, severity beyond the serious-event listing, or attribution. The absence of reported deaths in the listed information should not be taken as evidence that no deaths occurred; deaths are not reported in the registry record.

Overall, the registry record supports a description of the study design and measurement approach, but not a conclusion about the observed primary tumor outcome. Any stronger interpretation would require outcome results and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates a statistical distinction between defining an outcome and reporting its result. RECIST v1.0 supplies explicit criteria for complete response, partial response, stable disease, and progression, and the registry specifies an assessment window of up to 18 weeks after registration. Yet without the observed classifications, readers cannot evaluate the primary outcome, estimate its uncertainty, or compare it with another result.

The single-group design is also central to interpretation. A cohort can contribute descriptive information about measured outcomes and adverse events, but without a comparator it cannot directly estimate a between-group treatment contrast. This distinction is important when a study’s title or treatment rationale sounds comparative: the design determines what statistical claims the data can support.

The registry includes biomarker and progression-free survival outcomes in addition to safety and tumor response. Such outcomes can address different questions, but their interpretation depends on clear analysis populations, prespecified methods, and transparent reporting. The record lists the outcomes but does not report analyses or a statistical plan. This leaves uncertainty not only about the primary endpoint, but also about how the range of secondary questions was addressed.

Finally, the planning illustrations demonstrate why hypothetical sample-size calculations should be kept separate from the actual trial design and results. Their stated assumptions describe a planning exercise, including a two-arm allocation, while the study itself is recorded as single group. Reading those calculations as observed power or as the documented enrollment rationale would conflate distinct statistical purposes.

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 main trial-specific limitation in interpreting the registry record is the absence of the primary outcome result. The outcome definition and assessment timeframe are described, but the record does not give the number of participants in each tumor-response or progression category. It also does not report an estimate of uncertainty or the analysis population.

The single-group design has no concurrent comparator and no randomized treatment allocation. As a result, the design cannot directly distinguish outcomes associated with the treatment from outcomes that might have occurred for other reasons. The registry lists no masking, and it does not describe image-review procedures or whether outcome assessors were independent of treatment decisions.

The enrolled cohort consisted of 17 participants. The record does not report the rationale for that enrollment, the eligibility details beyond the listed melanoma conditions, or the degree to which the analyzed population matched the enrolled cohort. The analysis methods, missing-data procedures, interim analyses, and multiplicity approach are also not reported in the registry record.

The safety information is limited to participant counts and selected serious adverse-event terms with percentages. Event timing, duration, severity details, attribution, and the handling of recurrent events are not reported in the registry record. The reported counts therefore do not allow a full assessment of safety patterns or a comparison with another group.

These limitations concern what can be established from the registry record. They do not imply that unreported analyses or procedures were absent from the conduct of the study; those details are simply not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Temsirolimus and Bevacizumab in Treating Patients With Stage III or Stage IV Malignant Melanoma — NCT00397982.
• Registry record last updated 2017-06-09; status last verified 2017-05.
• Results first posted 2017-06-09.
• 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

NCT00397982 is a completed phase II, single-group study sponsored by the National Cancer Institute (NCI). It evaluated temsirolimus with bevacizumab in participants with stage III or stage IV melanoma. Enrollment was 17; the study started in 2008-01 and reached primary completion in 2013-07.

The primary outcome was objective tumor response and progression, assessed using RECIST v1.0 up to 18 weeks after registration. The registry record describes the endpoint but does not report its observed result. It lists six outcome measures and no analyses. Serious adverse events affected 9 participants among 17 at risk, and other adverse events affected 17 among 17 at risk. A comparator group, primary outcome estimate, analysis plan, missing-data procedures, and deaths are not reported in the registry record.