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 Bevacizumab With or Without MEDI-522 in Treating Patients With Unresectable or Metastatic Kidney Cancer (NCT00684996), a randomized phase 1, phase 2 study. The primary outcome is Progression-free Survival (Phase II).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00684996 |
| Phase | Phase 1, Phase 2 |
| Condition | Recurrent Renal Cell Cancer, Renal Cell Carcinoma, Stage III Renal Cell Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
Patients with unresectable or metastatic kidney cancer, described in the registry as recurrent, renal cell, stage III, or stage IV renal cell cancer. The primary-outcome description says the study was permanently closed to accrual on April 1, 2009, due to drug supply issues. The registry lists enrollment as 5.
Intervention
In the phase II combination arm, patients received bevacizumab at the phase I recommended phase II dose, together with MEDI-522. The arm description specifies intravenous MEDI-522 on days 1, 8, 15, and 22. The registry describes the study as investigating bevacizumab with or without MEDI-522.
Comparator
The phase II comparison was bevacizumab alone versus bevacizumab with MEDI-522. The monotherapy arm description specifies intravenous bevacizumab on days 1 and 15. The record identifies randomized allocation and an open-label parallel design, but does not report how many participants were assigned to each arm.
Primary question
The primary endpoint was progression-free survival in phase II: time from registration to the first observation of progressive disease, symptomatic deterioration, or death from any cause. The study asked whether adding MEDI-522 to bevacizumab changed this time-to-event outcome. A comparative result is not reported in the registry record.
This question is clinically and statistically framed as a comparison between two treatment strategies, not as a test of either treatment against no treatment. The combination arm included both agents, while the comparator arm included bevacizumab. Any estimate of the difference would therefore describe the added contribution of MEDI-522 in the context of bevacizumab, subject to the design and the data actually collected.
The registry’s study description also mentions side effects and dose selection. The phase I and phase II components have different roles: phase I was part of determining a dose for the combination arm, while the phase II component was randomized. The record does not report a completed comparison of progression-free survival, so the research question should not be mistaken for an answer about which arm had a better outcome.
3. Trial Design
This was a phase I and randomized phase II study with a parallel-group structure and no masking. The sponsor was the National Cancer Institute. The registry lists the study as terminated and enrollment as 5. The primary-outcome description says accrual was permanently closed on April 1, 2009, due to drug supply issues. The record lists a start in 2008-06 and primary completion in 2010-10.
The two phase II arms were bevacizumab alone and bevacizumab with MEDI-522. In the monotherapy arm, the described schedule was bevacizumab intravenously on days 1 and 15. In the combination arm, bevacizumab was given at the recommended phase II dose determined in phase I, with MEDI-522 intravenously on days 1, 8, 15, and 22. The registry does not report the numerical recommended phase II dose for bevacizumab in the combination arm.
Random allocation can help make the groups comparable at baseline, on average, when an adequately sized trial is conducted and the allocation process is implemented as intended. Here, the registry record does not state the number assigned to either arm, the allocation sequence method, or whether randomization was completed for all intended participants. With enrollment listed as 5 and early closure, the record does not establish that the planned phase II comparison accrued enough participants to support a stable estimate.
The registry describes both a phase I component and a randomized phase II component, but the available record does not explain the phase I dose-finding method, the planned phase II enrollment, or the design’s operating characteristics. Those details are not reported in the registry record. Consequently, the design labels identify the intended structure, while the posted enrollment and closure information show that the intended comparison must be interpreted cautiously.
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
| Stage | Phase I Bevacizumab (10 mg/kg) + MEDI-522 |
|---|---|
| STARTED | 5 |
| Eligible | 5 |
| COMPLETED | 0 |
| NOT COMPLETED | 5 |
Reasons for not completing this period:
| Reason | Phase I Bevacizumab (10 mg/kg) + MEDI-522 |
|---|---|
| Adverse Event | 1 |
| Refusal unrelated to adverse event | 1 |
| Progression/relapse | 2 |
| Other reasons not protocol specified | 1 |
Analysis population for the primary outcome, as defined in the registry: The study was permanently closed to accrual on April 1, 2009, due to drug supply issues.
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 | Phase I Bevacizumab (10 mg/kg) + MEDI-522 |
|---|---|---|
| Participants analysed | 5 | |
| Age, Continuous | years | 61.5 (45.3 to 80.8) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival (Phase II), measured over From date of registration to date of first observation of progressive disease, systemic deterioration, or death due to any cause, assessed up to 3 years.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
Progression-free survival was the phase II primary endpoint. The registry defines it from the date of registration until the first observation of progressive disease, symptomatic deterioration, or death from any cause. Participants known to be alive and progression-free at their last contact were to be censored at that contact. The stated assessment period was up to 3 years.
A time-to-event endpoint uses both whether an event occurred and how long participants remained without that event. Censoring allows a participant with no recorded event by their last observation to contribute information up to that time, without treating that participant as if they had remained event-free indefinitely. This is a general explanation of the method; the registry does not report how many participants were censored or when.
Progression-free survival is used to summarize the time until a defined disease-related event or death. It can capture more than one type of event, but the interpretation depends on consistent event definitions and ascertainment. Here, the endpoint description includes progressive disease, symptomatic deterioration, and death, while the broader timeframe refers to systemic deterioration. The registry record does not provide event counts, a median, a survival curve, a hazard ratio, or a confidence interval. Thus, the endpoint is specified, but its observed result cannot be assessed from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a primary endpoint and a randomized phase II comparison, but it does not report a numerical progression-free survival result. There is no posted treatment contrast, estimate of event time, confidence interval, or p-value in the registry record recorded. The central comparison—bevacizumab with MEDI-522 versus bevacizumab alone—therefore cannot be interpreted as showing a difference or no difference from the posted results.
The record lists enrollment as 5, and the study was permanently closed to accrual on April 1, 2009, due to drug supply issues. These registry entries are important context: the intended trial did not continue accrual as originally contemplated. They do not, by themselves, show how many participants entered the phase II randomization, how many received either regimen, or how many contributed to the primary endpoint. Those details are not reported in the registry record.
The absence of a reported outcome is not evidence that the two arms had equal outcomes. It also does not establish that one arm had better outcomes. A valid treatment comparison requires outcome data from the arms and an analysis that reflects the endpoint definition and follow-up. Since those results are absent here, statements about the magnitude, direction, or precision of any treatment effect would go beyond what is reported.
The registry’s safety summary has limited counts for a phase I group receiving bevacizumab with MEDI-522. It lists 3 at risk for serious events and 2 affected, as well as 3 at risk for other events and 3 affected. The record also lists allergic reaction/hypersensitivity at 66.7% and rigors/chills at 33.3% among the most frequent serious terms. These entries are descriptive safety information, not a comparison between randomized phase II arms. The record does not show whether these participants overlap with the primary-outcome population or provide the context needed to estimate comparative safety.
In general, a confidence interval describes the range of effect estimates compatible with the data and analysis under its assumptions. No confidence interval is reported, so precision cannot be judged. Likewise, no recorded analysis supports a claim about statistical significance. The appropriate reading is that the registry describes the intended question and some limited study information, while the comparative efficacy result is not reported in the registry record.
9. Statistical Methods Explained
The principal endpoint is a time-to-event outcome. In general, such an analysis considers the time from a defined origin to an event, while retaining information from participants whose event has not been observed by the end of their available follow-up. The registry specifies registration as the time origin and defines the event using progression, symptomatic deterioration, or death. It also says that participants last known to be alive and progression-free are censored at last contact.
Censoring is not the same as an event and does not mean that a participant had no event after their last contact. It marks the point beyond which the record does not establish their event status. Standard time-to-event methods rely on assumptions about the relationship between censoring and the chance of an event. This is a general statistical point; the registry does not report the censoring pattern or an assessment of those assumptions for this study.
For a randomized comparison, an analysis might summarize the progression-free survival distribution in each arm and estimate a contrast between them. Common summaries can include a survival curve, a median time, or a relative event-rate estimate. These are general examples, not results from this trial. The registry record does not report an analysis method, event counts, arm-specific estimates, or a comparative effect estimate. Its analysis entries do not include a reported analysis.
The study’s open-label design means that masking was listed as none. In general, lack of masking can affect care, reporting, or judgments about outcomes, especially when outcome definitions involve clinical assessment. A clearly specified endpoint and consistent assessment procedures can help make interpretation more reliable, but those procedures are not described in the registry record. Death is an objective event; progression and symptomatic deterioration require ascertainment according to the study’s definitions. The available record does not say how progression was assessed or how possible assessment differences were handled.
The phase I component is relevant because the combination arm used the recommended phase II dose determined in phase I. In general, dose-finding and efficacy comparison are distinct tasks: an early component may inform the dose used later, while a randomized component compares treatment strategies. The record does not report the dose-selection method, the dose-limiting toxicity definition, or the evidence used to select the recommended phase II dose. These elements should not be inferred from the arm description alone.
The study is described as randomized, but the record does not give the randomization procedure, allocation concealment, intended allocation ratio, or the number assigned to each arm. In general, allocation concealment concerns whether the upcoming assignment could be anticipated before enrollment. Randomization can reduce confounding, but it cannot ensure balance in every small sample. Given the listed enrollment of 5, the allocation and actual arm sizes are especially important context, yet they are not reported in the registry record.
The sample-size section is a planning illustration, not evidence of the trial’s original design or observed power. The stated illustration uses a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. For time-to-event outcomes, the illustration uses a total number of events, while other outcomes are expressed as participants per arm. These general planning quantities describe hypothetical requirements under stated assumptions. They do not establish what the trial planned, what it achieved, or whether a result was adequately powered. Sample sizes used in a planning illustration should not be described as observed power.
The record does not report a sample-size justification, target accrual, interim analysis plan, stopping boundary, primary statistical model, covariate adjustment plan, or approach to missing data. Those items are not reported in the registry record. Because accrual stopped due to drug supply issues, the study’s termination should not be recast as a statistically planned stopping decision without documentation. No such decision process is reported.
More generally, precision depends on the information available for the comparison, including the number of participants, events, and completeness of follow-up. A confidence interval would communicate uncertainty around an estimate; a p-value would summarize compatibility with a specified null model under the test’s assumptions. Neither is a substitute for an effect estimate and its context. Since the registry record does not report these analyses for progression-free survival, readers cannot assess the size or precision of the intended treatment contrast.
Over-dispersion is a general concern for count outcomes when variability exceeds what a simple model assumes; it can lead to confidence intervals that are too narrow if ignored. That concept does not establish a problem in this trial. The primary endpoint is time-to-event, and the registry does not report a count-model analysis. More broadly, statistical methods should match the outcome scale and design, but the registry record does not provide enough analysis detail to evaluate the method used for the primary endpoint.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome, progression-free survival in phase II, and a secondary outcome concerning the number of patients with grade 3 through grade 5 adverse events related to study drug. It also lists 6 outcome measures overall, but the details do not identify all of them or explain how they were prioritized. The record does not describe a multiplicity plan, such as a prespecified strategy for controlling the chance of false-positive findings across multiple endpoints or comparisons. That plan is not reported in the registry record.
Multiplicity matters in general when several outcomes, time points, subgroups, or statistical tests are examined. The more analyses that are considered, the more important it is to understand which were planned and how conclusions were selected. The registry does not report interim analyses or subgroup analyses, and none should be assumed. It also does not include a reported primary analysis to which a multiplicity procedure could be applied.
Missing-data handling is another important issue. For the primary endpoint, the registry defines censoring at last contact for participants known to be alive and progression-free. It does not report the amount of missing follow-up, the number censored, reasons for loss to follow-up, or sensitivity analyses addressing incomplete outcome ascertainment. In general, censoring methods require assumptions; the record does not provide information to assess them.
The analysis population is also not specified in the posted information. The record does not say whether the intended primary analysis was based on all randomized participants, participants who received treatment, or another defined group. It does not report the number randomized or analyzed by arm. With early closure and enrollment listed as 5, these omissions constrain interpretation, but do not justify assuming how participants were handled.
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 |
|---|---|---|---|
| Phase I Bevacizumab (10 mg/kg) + MEDI-522 | 2 | 3 | 66.7% |
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 |
|---|---|
| Phase I Bevacizumab (10 mg/kg) + MEDI-522 | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase I Bevacizumab (10 mg/kg) + MEDI-522 |
|---|---|---|
| Allergic reaction/hypersensitivity | Immune system disorders | 2 of 3 |
| Rigors/chills | General disorders | 1 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase I Bevacizumab (10 mg/kg) + MEDI-522 |
|---|---|---|
| Fatigue (asthenia, lethargy, malaise) | General disorders | 3 of 3 |
| Fever in absence of neutropenia, ANC lt1.0x10e9/L | General disorders | 2 of 3 |
| Rigors/chills | General disorders | 2 of 3 |
| Glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders | 2 of 3 |
| Hypertension | Vascular disorders | 2 of 3 |
| Hemoglobin | Blood and lymphatic system disorders | 1 of 3 |
| Diarrhea | Gastrointestinal disorders | 1 of 3 |
| Nausea | Gastrointestinal disorders | 1 of 3 |
| Pain - Esophagus | Gastrointestinal disorders | 1 of 3 |
| Flu-like syndrome | General disorders | 1 of 3 |
Serious events with the highest arm-level rate: allergic reaction/hypersensitivity (66.7%), rigors/chills (33.3%).
The registry’s safety summary describes a phase I group labeled bevacizumab (10 mg/kg) plus MEDI-522. It lists 3 at risk for serious events and 2 affected. For other events, it lists 3 at risk and 3 affected. These are counts in the posted summary, not comparative rates between randomized phase II arms. The registry record does not give further detail about event timing, recurrence, or participant-level overlap.
The listed top serious adverse-event terms are allergic reaction/hypersensitivity at 66.7% and rigors/chills at 33.3%. These percentages are quoted as recorded; the registry excerpt does not specify their denominator or show event counts for each term. They should not be read as percentages of all participants in the full trial or as evidence of a difference between arms.
The secondary outcome is described as the number of patients with grade 3 through grade 5 adverse events related to study drug. The summary figures above do not, in the available record, establish that they are counts for that exact outcome definition. The grade, relatedness, severity criteria, and handling of multiple events per patient are not reported. The small phase I group and the missing detail limit what can be concluded from these safety entries.
12. What the Result Does, and Does Not, Mean
This record is most informative about the study’s intended design and its interruption, rather than about comparative treatment results. It describes a phase I and randomized phase II study of bevacizumab with or without MEDI-522, with progression-free survival designated as the phase II primary endpoint. It also records that accrual was permanently closed on April 1, 2009, due to drug supply issues, and lists enrollment as 5.
The record does not report an estimate comparing progression-free survival between arms. Therefore, it cannot establish the direction or magnitude of a difference, nor the precision of any difference. The absence of a result in this record is not evidence that the treatments had the same outcomes, and it is not evidence that one treatment strategy was superior. It means the comparative outcome is not reported in the registry record.
The safety entries are limited to a phase I group and do not provide a randomized comparison. They can be read as descriptive entries recorded for that group, with the stated numbers at risk and affected and the listed serious-event terms. They do not support a broad assessment of relative safety, and they do not establish the incidence of events across the whole study population.
In general, a trial result is interpreted using the estimated effect, its uncertainty, the endpoint definition, and the amount and quality of follow-up. Here, the record provides the endpoint definition but not the outcome estimate or its uncertainty. Nor does it report the final analysis population, randomization counts by arm, or missing follow-up details. The registry record therefore documents a planned comparison that was curtailed, but it does not answer the comparison’s efficacy question.
This distinction matters: a trial’s question, design label, and outcome definition are not themselves results. Readers should not convert the existence of a randomized design into an assumption that a reliable treatment effect was estimated, especially when enrollment was limited and the record contains no primary-outcome analysis.
13. Why This Trial Matters Statistically
Statistically, this trial illustrates the difference between a planned comparison and an interpretable result. The registry identifies a randomized parallel phase II comparison and defines progression-free survival, but it does not report the comparative estimate or an analysis. Without those results, the design cannot be used to infer a treatment effect.
The closure information is also important. The record says accrual was permanently closed on April 1, 2009, because of drug supply issues, and lists enrollment as 5. This highlights how non-statistical constraints can limit the information a study ultimately collects. A trial’s ability to answer its question depends not only on its endpoint and design, but also on actual accrual, event information, follow-up, and complete reporting. The registry does not provide enough detail to assess those elements fully.
The endpoint definition shows why protocol-level detail matters. Progression-free survival combines progression, symptomatic deterioration, or death, and includes censoring for participants last known to be alive and progression-free. In general, interpretation depends on consistent event assessment and a transparent account of censoring. Those features cannot be evaluated from the outcome definition alone.
Finally, the planning illustrations must be kept separate from the trial’s own design and results. General sample-size calculations can show how assumptions influence a hypothetical requirement, but they do not recreate an unreported protocol justification or compensate for missing outcome data. This study is statistically notable as a case where the registry documents the question and early closure, while leaving the principal comparative result unavailable.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most consequential limitation for interpreting this study is that the registry record does not report a progression-free survival result. It gives no arm-specific outcome summaries, comparative estimate, confidence interval, p-value, or event count. Thus, the principal efficacy question cannot be answered from the posted information.
The record lists enrollment as 5, but does not report how many participants were randomized, assigned to each phase II arm, treated, followed, or included in an analysis. It also does not explain how participants in the phase I component relate to the phase II population. These omissions prevent a clear accounting of the analysis population.
Accrual was permanently closed on April 1, 2009, due to drug supply issues, and the study status is listed as terminated. The registry does not report whether the closure altered the analysis plan, whether follow-up continued, or whether any planned endpoint analysis was performed outside the posted record. Those details are not reported in the registry record.
Other design and analysis details are also absent, including the allocation procedure, target enrollment, sample-size justification, event-assessment procedures, missing-data methods, interim analyses, and primary statistical model. The study is unmasked, but the record does not describe safeguards for outcome assessment. These gaps limit evaluation of bias, precision, and reproducibility.
The safety summary is narrow: it concerns a phase I combination group and provides limited counts and serious-event terms. The registry does not supply enough context to interpret these as comparative safety results, and the secondary outcome’s grade and relatedness criteria are not tied explicitly to the listed figures in the available information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Bevacizumab With or Without MEDI-522 in Treating Patients With Unresectable or Metastatic Kidney Cancer — NCT00684996.
- Registry record last updated 2014-05-15; status last verified 2013-04.
- Results first posted 2014-01-14.
- 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 NCT00684996 as a phase I and randomized phase II study of bevacizumab with or without MEDI-522 in patients with unresectable or metastatic kidney cancer. The parallel-group study was unmasked. The phase II arms were bevacizumab alone and bevacizumab with MEDI-522, with the combination dose of bevacizumab determined in phase I.
Progression-free survival was the phase II primary endpoint, measured from registration to progression, symptomatic deterioration, or death, with censoring at last contact for participants known to be alive and progression-free. The record lists enrollment as 5 and says accrual was permanently closed on April 1, 2009, due to drug supply issues. The study status is terminated.
A comparative primary-outcome result is not reported in the registry record. Limited phase I safety figures are listed, but they do not constitute a randomized safety comparison. The record does not provide enough analysis detail to assess the intended treatment contrast.