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 Carboplatin, Paclitaxel, and Bevacizumab With or Without Everolimus in Treating Patients With Metastatic Malignant Melanoma (NCT00976573), a randomized phase 2 study. The primary outcome is Progression-free Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00976573 |
| Phase | Phase 2 |
| Condition | Melanoma (Skin) |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 149 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Alliance for Clinical Trials in Oncology |
| Results posted | Yes |
2. Clinical Question
Population
Participants had malignant melanoma that had spread from its original site to other parts of the body. The primary analysis population is described as all participants enrolled, under an intent-to-treat approach. The registry record lists an enrollment of 149.
Intervention
One arm received bevacizumab, paclitaxel, and carboplatin. The other received those same medicines with everolimus. The registry describes bevacizumab and the chemotherapy drugs as intravenous treatments; everolimus was taken by mouth on 3 days a week. Treatment courses were planned to repeat every 28 days while disease had not progressed and toxicity remained acceptable.
Comparator
The comparison was the three-drug regimen without everolimus versus that regimen with everolimus. The trial is recorded as randomized, parallel-group, and unmasked. The registry record does not report details about how the random sequence was generated or concealed.
Primary question
The primary question was how progression-free survival compared between the treatment arms. It was defined as time from randomization to documented disease progression or death without documented progression. Progression was assessed using RECIST criteria, including specified changes in target lesions or the appearance of new lesions. The registry record does not report a sponsor-estimated hazard ratio or a formal between-arm test for this endpoint.
3. Trial Design
This was a randomized phase II trial with a parallel-group design and no masking recorded in the registry. It enrolled participants with metastatic malignant melanoma and compared a regimen of bevacizumab, paclitaxel, and carboplatin against the same regimen with everolimus added. The registry lists 149 participants enrolled. It does not report the randomization procedure, allocation concealment, or the details of how participants were assigned to arms.
In Arm A, participants received bevacizumab on days 1 and 15, paclitaxel on days 1, 8, and 15, and carboplatin on day 1. In Arm B, the same medicines were given, with everolimus taken by mouth daily on 3 days a week. Courses were scheduled every 28 days in the absence of disease progression or unacceptable toxicity. These are registry descriptions of the planned regimens; the record does not provide individual treatment exposure or adherence information.
The primary endpoint was progression-free survival, with a stated timeframe of up to 5 years. The primary analysis population is described as all enrolled participants. The posted arm results include 75 participants for Arm A and 74 for Arm B. The registry lists the trial as completed, with a start date of 2010-04 and primary completion in 2014-12. Further details about recruitment, follow-up completeness, or protocol deviations are not reported in the registry record.
The registry also identifies toxicity, confirmed tumor response, and overall survival as secondary outcomes. It posts results for confirmed tumor response and adverse events, but it does not report a result for overall survival in the record. The registry record does not report a sample-size justification or a planned interim-analysis scheme.
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 | Arm A (Bevacizumab, Paclitaxel, and Carboplatin) | Arm B (Bevacizumab, Paclitaxel, Carboplatin, and Everolimus) |
|---|---|---|
| STARTED | 75 | 74 |
| COMPLETED | 71 | 71 |
| NOT COMPLETED | 4 | 3 |
Reasons for not completing this period:
| Reason | Arm A (Bevacizumab, Paclitaxel, and Carboplatin) | Arm B (Bevacizumab, Paclitaxel, Carboplatin, and Everolimus) |
|---|---|---|
| Ineligible | 0 | 1 |
| Cancel prior to receiving treatment | 4 | 2 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat analysis population: All participants enrolled are included in the primary analysis.
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 | Arm A (Bevacizumab, Paclitaxel, and Carboplatin) | Arm B (Bevacizumab, Paclitaxel, Carboplatin, and Everolimus) | Total |
|---|---|---|---|---|
| Participants analysed | 75 | 74 | 149 | |
| Age, Continuous | years | 59 (26 to 85) | 58 (29 to 81) | 59 (26 to 85) |
| Sex: Female, Male: Female | Participants | 21 | 33 | 54 |
| Sex: Female, Male: Male | Participants | 54 | 41 | 95 |
| Region of Enrollment: United States | participants | 75 | 74 | 149 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival, measured over Time from randomization to documentation of disease progression or death without documentation of progression;Up to 5 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival measures the time from randomization until disease progression is documented or death occurs without documented progression. It combines these events into a time-to-event outcome. A participant who has not had a recorded event by the end of observation contributes information up to the last relevant follow-up point, rather than being treated as if an event had occurred.
The registry defines progression using RECIST criteria. For target lesions, the definition includes a relative increase of at least 20% in the sum of diameters, measured from the smallest sum recorded during the study, together with an absolute increase of at least 5 mm. New lesions can also qualify as progression. The definition additionally addresses unequivocal progression of non-target lesions and emphasizes that progression should reflect overall disease status rather than an isolated lesion change.
A time-to-event endpoint is useful when the timing of progression or death matters and participants may be followed for different lengths of time. The Kaplan-Meier method, which the registry names for estimating the distribution of progression-free survival, accounts for incomplete follow-up by retaining information from participants up to their last observed time. The posted results express the endpoint as a median in months with a 95% confidence interval. The registry record does not report a sponsor-estimated hazard ratio or a formal comparative test for progression-free survival.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted median progression-free survival was 5.6 months for Arm A, with a 95% confidence interval of 4.7 to 8.3 months. For Arm B, the median was 5.1 months, with a 95% confidence interval of 3.9 to 6.7 months. These are estimates of the time by which half of the estimated progression-free survival distribution had experienced progression or death. They are not estimates of how long every participant remained free of an event.
The confidence intervals describe uncertainty around each arm’s median estimate. The intervals overlap, so the registry’s arm-specific estimates do not by themselves establish a clear between-arm difference. More fundamentally, comparing two medians is not the same as testing the full time-to-event distributions. The registry record does not report a hazard ratio, a confidence interval for a comparative effect, or a sponsor-reported p-value for the primary endpoint. Without those comparative results, the posted medians should be read descriptively rather than as evidence of a statistically established difference.
The confirmed tumor response results are another part of the record, but they answer a different question from progression-free survival. The posted response rates were 13.0% for Arm A and 23.0% for Arm B; their respective 95% confidence intervals were 6.0% to 22.7% and 13.5% to 34.0%. The registry also posts an unadjusted p-value of 0.127 for the response comparison. This is not a primary-endpoint test and does not replace a comparative analysis of progression-free survival. The response estimates are uncertain, as reflected in their confidence intervals, and the registry record does not report adjusted secondary analyses.
The adverse-event information describes reported events in the safety groups. Serious adverse events were reported for 12 of 71 participants at risk in Arm A and 18 of 71 in Arm B. These counts describe observed events in the registry’s safety reporting and should not be interpreted as a causal comparison. The record does not include a comparative statistical analysis of these safety data or a count of deaths reported as adverse events.
Overall, the record supplies arm-specific primary endpoint summaries and selected secondary and safety results, but not a sponsor-reported comparative analysis of progression-free survival. That absence limits how firmly the primary results can be interpreted as evidence about a difference between regimens. The estimates remain descriptive summaries of the trial data.
9. Statistical Methods Explained
The statistical methods named in the registry are limited. It says progression-free survival distributions will be estimated using the Kaplan-Meier method, and it reports medians with 95% confidence intervals. It does not report the model or test used for a formal comparison of progression-free survival. General explanations below describe what these methods mean; they do not assert that an unreported analysis was performed.
What does the Kaplan-Meier method estimate?
General: The Kaplan-Meier method estimates the probability of remaining free of an event over time. At each event time, the estimate uses the participants still under observation and at risk immediately before that time. Participants whose follow-up ends without a recorded event are censored at their last known event-free time. Censoring preserves the information available up to that point; it does not mean the participant had an event or remained event-free indefinitely.
The method relies on assumptions about follow-up, including that the reason observation ends does not systematically conceal a participant’s underlying event risk, after accounting for the design and information available. The registry record does not describe censoring patterns, follow-up completeness, or checks of those assumptions. The stated primary endpoint includes progression or death without documented progression, so either event can contribute to the endpoint.
What does a median and its confidence interval convey?
General: The median time-to-event is the time at which the estimated event-free proportion reaches one half. A confidence interval gives a range of values compatible with the data under the method’s assumptions and provides a sense of estimation uncertainty. A wider interval indicates less precision than a narrower interval, although the amount of uncertainty also depends on the analysis and its assumptions. The registry reports Arm A’s median as 5.6 months, with a 95% confidence interval of 4.7 to 8.3 months, and Arm B’s median as 5.1 months, with a 95% confidence interval of 3.9 to 6.7 months.
Those intervals concern each arm’s median separately. They are not a confidence interval for the difference between arms and do not themselves supply a formal test of the treatment comparison. A comparative time-to-event analysis may use all observed event times, rather than reducing each arm’s distribution to a single median. The registry record does not report the sponsor’s comparative estimate, such as a hazard ratio, for progression-free survival.
Why does the endpoint definition matter?
Progression-free survival depends on how progression is identified and on the timing of assessments. The registry refers to RECIST criteria and gives a detailed definition involving target lesions, new lesions, and non-target lesions. Consistent assessment rules matter because different progression classifications or assessment schedules could change when an event is recorded. The registry record does not report the imaging schedule, who assessed scans, or whether assessments were centrally reviewed.
General: In an unmasked trial, knowledge of assigned treatment can potentially influence decisions or assessments that involve judgment. This does not establish that bias occurred in this study. It is a reason to consider whether outcome measurement is objective, standardized, and conducted consistently. The registry identifies the trial as unmasked but does not report additional safeguards for progression assessment.
How should the response comparison be read?
The response outcome counts complete or partial response under RECIST criteria. The registry posts rates of 13.0% for Arm A and 23.0% for Arm B, with 95% confidence intervals of 6.0% to 22.7% and 13.5% to 34.0%, respectively. It also posts an unadjusted p-value of 0.127 for the comparison. General: A p-value describes how compatible observed data are with a specified null model, subject to the analysis assumptions; it is not the probability that the null hypothesis is true, nor does it quantify the size or clinical importance of an effect. The record does not describe adjustment for multiple outcome comparisons.
The sample-size illustrations are planning calculations based on fractions of the observed response effect under stated assumptions, including a two-sided significance level of 0.05, equal allocation, and a normal approximation. They are hypothetical planning scenarios, not observed power for this completed trial and not evidence that the original trial was designed around those assumptions. The registry record does not report the trial’s own sample-size justification.
What remains unknown about analysis conduct?
The registry’s primary endpoint description names Kaplan-Meier estimation, but further analysis details are not reported in the registry record. These include the comparative test, any covariate adjustment, handling of missing or incomplete endpoint assessments, and sensitivity analyses. The record describes the primary analysis population as all enrolled participants, but does not give more detail about exclusions, deviations, or the treatment of participants with unavailable outcome data. Such details are important for judging the robustness of an estimate, especially when follow-up or outcome assessment is incomplete.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists progression-free survival as the primary endpoint and identifies toxicity, confirmed tumor response, and overall survival as secondary outcomes. It does not report a strategy for controlling multiplicity across endpoints, comparisons, or repeated analyses. The response comparison is posted with an unadjusted p-value, and no adjusted secondary analyses are listed. Without a stated multiplicity plan, secondary p-values should be read cautiously: testing several outcomes can increase the likelihood that at least one result appears unusual by chance. This general concern does not determine the result of any particular comparison.
The registry record does not report an interim-analysis plan, stopping boundaries, or sequential-testing adjustments. It also does not report a protocol-level statistical analysis plan or explain whether the posted analyses were prespecified. These omissions prevent a reader from assessing whether the reported secondary results reflect a planned testing hierarchy or a broader set of analyses.
For missing data, the record describes the primary population as all participants enrolled and says progression-free survival is estimated using Kaplan-Meier methods. The registry does not report the number or pattern of missing assessments, the frequency or reasons for loss to follow-up, or how missing response data were handled. It also does not report sensitivity analyses examining how incomplete follow-up might affect the results. General: Time-to-event methods can use partial follow-up through censoring, but that approach depends on assumptions about how censoring relates to event risk. The record does not provide enough detail to assess those assumptions in this trial.
The registry’s description of the intent-to-treat population is useful because it states that enrolled participants are included in the primary analysis. However, it does not give a participant-level accounting of analysis availability or explain whether any enrolled participants lacked an evaluable endpoint. The record also does not report how treatment discontinuation, protocol deviations, or crossover, if any, were addressed. These details are not reported in the registry record and should not be inferred from the arm summaries.
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 |
|---|---|---|---|
| Arm A (Bevacizumab, Paclitaxel, and Carboplatin) | 12 | 71 | 16.9% |
| Arm B (Bevacizumab, Paclitaxel, Carboplatin, and Everolimus) | 18 | 71 | 25.4% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm A (Bevacizumab, Paclitaxel, and Carboplatin) | 71 of 71 |
| Arm B (Bevacizumab, Paclitaxel, Carboplatin, and Everolimus) | 71 of 71 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A (Bevacizumab, Paclitaxel, and Carboplatin) | Arm B (Bevacizumab, Paclitaxel, Carboplatin, and Everolimus) |
|---|---|---|---|
| Neutrophil count decreased | Investigations | 4 of 71 | 5 of 71 |
| Platelet count decreased | Investigations | 2 of 71 | 2 of 71 |
| Nausea | Gastrointestinal disorders | 1 of 71 | 2 of 71 |
| Fatigue | General disorders | 2 of 71 | 1 of 71 |
| White blood cell decreased | Investigations | 2 of 71 | 1 of 71 |
| Thromboembolic event | Vascular disorders | 1 of 71 | 2 of 71 |
| Abdominal pain | Gastrointestinal disorders | 1 of 71 | 1 of 71 |
| Vomiting | Gastrointestinal disorders | 1 of 71 | 1 of 71 |
| Sepsis | Infections and infestations | 0 of 71 | 2 of 71 |
| Urinary tract infection | Infections and infestations | 0 of 71 | 2 of 71 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A (Bevacizumab, Paclitaxel, and Carboplatin) | Arm B (Bevacizumab, Paclitaxel, Carboplatin, and Everolimus) |
|---|---|---|---|
| Fatigue | General disorders | 68 of 71 | 67 of 71 |
| Anemia | Blood and lymphatic system disorders | 63 of 71 | 59 of 71 |
| White blood cell decreased | Investigations | 54 of 71 | 55 of 71 |
| Neutrophil count decreased | Investigations | 49 of 71 | 59 of 71 |
| Platelet count decreased | Investigations | 47 of 71 | 50 of 71 |
| Nausea | Gastrointestinal disorders | 40 of 71 | 46 of 71 |
| Hypertension | Vascular disorders | 39 of 71 | 37 of 71 |
| Peripheral sensory neuropathy | Nervous system disorders | 36 of 71 | 29 of 71 |
| Abdominal pain | Gastrointestinal disorders | 24 of 71 | 24 of 71 |
| Vomiting | Gastrointestinal disorders | 22 of 71 | 25 of 71 |
Serious events with the highest arm-level rate: neutrophil count decreased (7.0%), nausea (2.8%), fatigue (2.8%), sepsis (2.8%), urinary tract infection (2.8%).
The registry reports serious adverse events for 12 of 71 participants at risk in Arm A and 18 of 71 participants at risk in Arm B. These are descriptive counts. The record does not provide a comparative statistical analysis, and the counts alone do not show whether any difference is attributable to treatment. The safety groups may also differ from the primary analysis population, so the safety denominators should be read as reported rather than assumed to match the primary endpoint denominators.
Among the serious adverse-event terms listed, neutrophil count decreased is reported at 7.0%. Nausea, fatigue, sepsis, urinary tract infection, and platelet count decreased are each reported at 2.8%. The registry does not identify these listed term percentages by treatment arm in the posted information, so they should not be assigned to one arm or interpreted as arm-specific comparisons.
The record lists 71 participants at risk for other adverse events and 71 affected in each arm. This broad reporting does not describe event severity, duration, or the number of events per participant. Adverse-event deaths are not reported in the registry record. The data therefore provide a limited descriptive safety account, not a complete comparative assessment of harms.
12. What the Result Does, and Does Not, Mean
The registry record shows arm-specific estimates of progression-free survival and selected secondary and safety outcomes for a randomized phase II trial. The primary endpoint was defined in advance as time from randomization to documented progression or death without documented progression. The reported medians summarize each arm’s estimated time-to-event distribution, while their confidence intervals express uncertainty around those medians.
These summaries do not, on their own, establish that the regimens differ in progression-free survival. The record does not report a sponsor-estimated hazard ratio, a confidence interval for a comparative effect, or a formal primary-endpoint test. Nor should the arm-specific medians be treated as complete descriptions of the survival distributions: participants can have different event times, and follow-up may be censored. The absence of a reported comparative analysis is an important limit on interpretation.
The response results and adverse-event summaries add information about outcomes recorded in the trial, but they do not resolve that limitation. Response is a separate endpoint, and its posted comparison is unadjusted. The record does not report an overall survival result or an adjustment strategy for multiple secondary comparisons. Safety counts are descriptive and do not establish that treatment caused or prevented an event.
General: Statistical uncertainty is distinct from clinical importance. A confidence interval describes uncertainty under a statistical method; it does not determine whether an effect would matter to patients or clinicians. That judgment also depends on clinical context and evidence beyond these registry summaries. No medical advice or treatment recommendation follows from the posted results alone. The record is best read as a report of trial design and selected estimates, with important comparative and analysis details not reported in the registry record.
13. Why This Trial Matters Statistically
This trial presents several statistical issues common to randomized clinical research. Its primary outcome is time-to-event, so analysis must account for the timing of progression or death and for participants whose event status is not observed through the full follow-up period. A median provides an accessible summary, but it compresses the underlying event-time distribution. The registry’s Kaplan-Meier description is relevant to that outcome, while the absence of a reported comparative analysis limits conclusions about between-arm differences.
The unmasked, parallel-group design also makes outcome measurement worth considering. Randomization supports a structured comparison of assigned regimens, but it does not eliminate concerns about missing follow-up, assessment practices, or imbalances that arise by chance. The registry gives the progression criteria but does not report scan schedules, central review, or the handling of incomplete assessments. Those details would help readers evaluate how consistently the endpoint was measured.
Multiplicity matters because the trial includes several secondary outcomes and the record posts an unadjusted response comparison. If several endpoints are examined, selective emphasis on a result can overstate the strength of evidence unless the testing strategy is clear. The registry does not report such a strategy, so secondary results warrant cautious interpretation.
The record also illustrates why complete statistical reporting matters. Arm-specific medians and confidence intervals are informative, but a comparative effect estimate and its uncertainty would more directly address the primary question. Reporting the analysis population, missing-data handling, and sensitivity analyses would further clarify how robust the results are. These are general statistical considerations; the registry record does not establish that any particular bias or analysis problem occurred.
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 limitation for statistical interpretation is that the registry record does not report a comparative analysis of the primary endpoint. It provides a median and 95% confidence interval for each arm, but no sponsor-estimated hazard ratio, confidence interval for a comparative effect, or p-value for progression-free survival. This leaves the central between-arm question without a reported inferential result.
Further limitations arise from incomplete analysis detail. The record does not describe the randomization sequence or allocation concealment, scan schedule, central review of progression, censoring patterns, or handling of missing assessments. It does not report whether any participants were excluded from an endpoint analysis or provide sensitivity analyses. The stated intent-to-treat population is helpful, but the record does not give a detailed accounting of outcome availability.
The trial is listed as unmasked, which is relevant when considering endpoint assessment. This is not evidence that assessment bias occurred; the registry does not report whether additional safeguards were used. The registry also does not report the sample-size justification, interim-analysis plan, or multiplicity strategy. These omissions make it difficult to assess the intended precision and testing framework.
The secondary information is limited as well. The registry posts a response comparison but no overall survival result, and it does not list sponsor analyses for the secondary outcomes. Safety figures are descriptive, with no comparative analysis reported. The record’s adverse-event term percentages are not identified by treatment arm, and adverse-event deaths are not reported. These gaps constrain interpretation of both efficacy-related and safety findings without implying that unreported results were unfavorable or absent from other records.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Carboplatin, Paclitaxel, and Bevacizumab With or Without Everolimus in Treating Patients With Metastatic Malignant Melanoma — NCT00976573.
- Registry record last updated 2017-04-04; status last verified 2017-03.
- Results first posted 2017-03-07.
- 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
NCT00976573 is a completed, randomized phase II trial of bevacizumab, paclitaxel, and carboplatin with or without everolimus in metastatic malignant melanoma. The registry lists an enrollment of 149, a start date of 2010-04, and primary completion in 2014-12. The design is parallel-group and unmasked.
Progression-free survival was the primary endpoint, defined as time from randomization to documented progression or death without documented progression. Arm-specific medians and 95% confidence intervals are posted, but the registry record does not report a sponsor comparative analysis for this endpoint. The record also includes confirmed tumor response and adverse-event information. It does not report an overall survival result, a multiplicity strategy, or details of missing-data handling. The findings are therefore most appropriately read as descriptive registry results with important comparative-analysis details not reported.