Abraxane and Avastin as Therapy for Patients With Malignant Melanoma, a Phase II Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Abraxane and Avastin as Therapy for Patients With Malignant Melanoma, a Phase II Study (NCT00462423), a non-randomized phase 2 study. The primary outcome is Progression-free Survival (PFS) at 4 Months.

2. Clinical Question

The clinical question is whether the combination can be evaluated for safety and activity as first-line therapy in the described population. The trial's design addresses that question within a single treated group; it does not directly estimate how outcomes would differ under another treatment or under no treatment. The registry lists overall survival, progression-free survival, objective response, time to objective response, and safety and tolerability among secondary outcomes. Those outcome descriptions identify what the study intended to assess, but the registry record does not report their numerical results. The primary endpoint is more narrowly defined: it concerns the percentage of participants who are progression-free at the specified assessment time, rather than a comparison of treatment effects between groups.

3. Trial Design

This was a Phase II, multicenter, open-label, single-group study of Abraxane and Avastin in patients with unresectable metastatic malignant melanoma. The registry classifies allocation as non-randomized and the study model as single-group. There was no masking. Enrollment was 50, and the study status is completed. The record lists a start in 2007-04 and primary completion in 2011-04.

The registry summary describes the intended population as males and females 18 years of age or older with measurable metastatic melanoma, and describes the combination as first-line therapy. Abraxane was to be given through a 30-minute IV infusion weekly for three weeks at 150 mg/m2, followed by one week of rest in a 28-day cycle. Avastin was to be given at 10 mg/kg every two weeks without a rest period. The summary says disease progression was to be evaluated every two months. Participants without progression or unacceptable toxicity were to be offered ongoing therapy until progression or unacceptable toxicity.

These details describe the study plan in the registry summary, not the extent to which every participant received the planned treatment or completed follow-up. Actual treatment exposure, adherence, discontinuations, and follow-up completeness are not reported in the registry record. Because all participants were in one study group and treatment assignment was not randomized, the design can describe outcomes among those studied but cannot separate treatment effects from other explanations for observed outcomes. The registry record does not report further details of the multicenter organization, site-level enrollment, or a statistical analysis plan.

4. Participant Flow and Accounting

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

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival (PFS) at 4 Months, measured over 4 months..

The primary endpoint is progression-free survival at four months from first treatment, determined by RECIST 1.0. The stated unit is the percentage of patients. In general, progression-free survival concerns the time during which a participant remains alive without documented disease progression; a fixed-time measure describes the proportion meeting that status at a specified assessment time. The registry describes this endpoint at four months, rather than reporting a treatment-versus-control difference.

In general, a fixed-time progression-free survival measure can provide a clinically interpretable snapshot of disease status by a specified point in follow-up. It is distinct from a median time-to-event result, which describes the time by which a specified portion of a group has experienced an event. The endpoint definition also depends on how progression and assessment are determined. The registry names RECIST 1.0 as the assessment framework and identifies the time origin as first treatment.

The registry record does not report the percentage progression-free at four months, the number assessed, the 95% confidence interval, or details of missing endpoint observations. As a result, the direction and precision of the primary endpoint estimate cannot be evaluated from this record. The endpoint definition alone does not establish what the study found.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

This study enrolled one treatment group and was non-randomized and unmasked. In general, a single-group trial can describe outcomes observed among participants who receive the study regimen. It does not create a concurrent control group, so it cannot estimate a randomized contrast between the regimen and another treatment. A comparison to an external benchmark, if attempted, would require careful consideration of differences in eligibility, follow-up, outcome assessment, and other factors. The registry record does not report an external comparator or a comparative analysis.

Open-label means the study did not use masking, according to the registry classification. In general, knowledge of treatment can influence care decisions, reporting, and assessment, especially when outcomes involve judgment. RECIST 1.0 provides a named framework for assessing disease response and progression, but the registry record does not provide details of how assessments were reviewed or whether independent review was used.

What does the primary endpoint mean?

The primary endpoint is progression-free survival at four months from first treatment, expressed as a percentage of patients. In general, a fixed-time percentage is an estimate of the share of a defined analysis group meeting an outcome condition at that time. Its interpretation depends on the definition of progression, the time origin, the analysis population, and how participants without an observed assessment are handled. The registry names RECIST 1.0 and first treatment as the assessment framework and time origin, but the analysis population and missing-data procedures are not reported in the registry record.

The registry identifies a 95% confidence interval as the dispersion measure. In general, a confidence interval communicates the statistical uncertainty associated with an estimate under a specified method and its assumptions. A narrower interval generally indicates greater precision than a wider one, but precision is not the same as freedom from bias. A confidence interval does not account automatically for limitations such as lack of a control group, outcome misclassification, or incomplete follow-up. Because the numerical estimate and interval are not reported, the precision of this endpoint cannot be judged.

How should event-count outcomes be understood?

In general, a binary outcome records whether each participant did or did not experience an event during a defined period. A percentage summarizes the share with the event, while its uncertainty depends in part on the number of participants with usable outcome information and on the analysis method. The registry identifies the primary endpoint unit as a percentage but does not report the result or denominator used for its analysis. Enrollment is not necessarily the same as the number included in an endpoint analysis.

The safety record reports participants at risk and participants affected for serious and other adverse events. These counts describe the registry's recorded safety group; they should not be interpreted as proof that the study drugs caused the events. In general, adverse event counts are affected by the definitions used, the observation period, how events are collected, and whether participants have comparable follow-up. Those procedural details are not reported in the registry record.

What analysis details are unavailable?

The registry record does not report the statistical analysis plan, hypothesis tests, analysis populations, handling of missing observations, censoring rules, or any adjustments. It also does not report interim analyses or a sample-size justification. These omissions mean that readers cannot determine from the record which participants contributed to each endpoint, what exact statistical procedure was used, or whether planned analyses differed from those ultimately conducted.

In general, missing-data handling is important because participants without an observed outcome may differ from those with complete follow-up. Methods for time-to-event outcomes often account for follow-up that ends before an event, but the specific approach and assumptions must be stated to interpret a result. The registry record does not provide such detail for this study. A listed endpoint name, timeframe, or confidence-interval label does not substitute for a reported analysis method or result.

There are also secondary outcomes listed, including overall survival, objective response, time to objective response, and safety and tolerability. In general, assessing multiple outcomes can raise multiplicity questions: when many outcomes or tests are examined, the chance of at least one apparently unusual result may increase if no adjustment or hierarchy is used. The registry record does not report a multiplicity strategy, specific tests, or numerical secondary results. It is therefore not possible to assess how multiple analyses were handled or to reinterpret the results using a different method.

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("Single Arm, Open Label")
n      <- c(50)
events <- c(38)
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  Single Arm, Open Label  50  38  76.0  61.8  86.9  62.6  85.7  62.5  85.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcome areas, but it does not report a statistical analysis plan, inferential tests, or a strategy for handling multiplicity. In general, multiplicity arises when multiple outcomes, time points, or statistical comparisons are examined. Without a stated plan, readers cannot tell whether the study treated one endpoint as confirmatory, whether secondary results were exploratory, or whether any adjustment to inference was intended. Numerical results for the listed secondary outcomes are not reported in the registry record.

The record does not describe the analysis population for the primary endpoint or the secondary outcomes. Enrollment is reported as 50, but that figure alone does not establish how many participants were included in each analysis. The record also does not report the number with an observed four-month assessment, reasons for missing assessments, or procedures for handling missing endpoint data. These details matter because a percentage estimate depends on which participants are included and how unavailable outcomes are treated.

For time-to-event outcomes, censoring rules and the handling of incomplete follow-up are also important. In general, censoring means that an event time is not observed for some participants during their available follow-up; statistical methods rely on assumptions about that incomplete information. The registry record does not report the specific methods or assumptions used for progression-free or overall survival. It also does not report interim analyses or a prespecified analysis plan. Accordingly, the available record supports only a limited description of intended outcomes, not a detailed reconstruction of the analyses.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnea (4.0%), atrial flutter (2.0%), hemoptysis (2.0%), small intestinal perferation (2.0%), supraventricular tachycardia (2.0%).

The registry reports safety counts for the single study group. It lists 50 at risk and 13 affected for serious adverse events, and 50 at risk and 11 affected for other adverse events. These are counts as recorded, not evidence on their own that an event was caused by treatment. The registry record does not report deaths in the serious-adverse-event group details.

The listed serious-event terms include Dyspnea at 4.0%, Atrial Flutter at 2.0%, Hemoptysis at 2.0%, Small intestinal perferation at 2.0%, Supraventricular tachycardia at 2.0%, and Nephrotic syndrome at 2.0%. These term-specific entries should be read as registry safety descriptions, not as comparative risks: the study has no control group. The record does not provide a full account of event timing, duration, severity criteria, recurrence, attribution, or follow-up for each event.

In general, safety counts depend on the study's event definitions and observation procedures. Without those details and a concurrent comparator, the counts cannot establish whether event frequency differs from another treatment or background risk. They also should not be confused with the primary progression-free survival result, which is not reported in the registry record.

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

The registry record establishes that this completed Phase II study evaluated Abraxane and Avastin in a single, open-label, non-randomized group of patients with unresectable metastatic malignant melanoma. It describes the intended treatment schedule and identifies four-month progression-free survival by RECIST 1.0 as the primary endpoint. It also lists secondary outcome areas and reports some safety counts.

What the record does not establish is the numerical primary endpoint result. The four-month progression-free survival percentage and its 95% confidence interval are not reported in the registry record. Without those values, readers cannot assess the observed level of progression-free survival or the statistical precision of that estimate. Numerical results for the listed secondary outcomes are also not reported.

The design also limits the type of conclusion the study could support. In general, a single treated group can describe observed outcomes, but it does not provide a randomized comparison with another treatment. Outcomes cannot be attributed to the regimen alone based on this design, because other influences on disease course and outcome assessment are not controlled by random assignment. The record does not identify a comparator group.

The safety counts and serious-event terms are descriptive. They are not, by themselves, proof of causation or a comparison of risk. The record does not report the details needed to fully understand event ascertainment, attribution, or follow-up.

Thus, the registry supports understanding of the study's question and design, but not a conclusion about the magnitude of the primary endpoint result, its precision, or comparative treatment effects. These limits reflect what is and is not reported in the registry record, rather than an inference that the study had no results.

14. Why This Trial Matters Statistically

This trial illustrates how a defined endpoint and a completed study status are not enough to interpret efficacy. The registry specifies progression-free survival at four months, an assessment framework, a time origin, and a confidence-interval measure. Yet the endpoint estimate and interval are not reported in the registry record. Without them, the central efficacy question cannot be answered from the registry entry.

It also shows why design and estimation must be considered together. A single-group study can characterize outcomes within the treated group, but it does not supply a randomized comparator. In general, an observed outcome proportion is descriptive of the analyzed group and period; it is not automatically a causal estimate of treatment benefit. The non-randomized, unmasked design makes it particularly important to distinguish the study's intended question from the stronger comparative claims that this design cannot directly test.

The entry also makes visible the distinction between outcome labels and analysis reporting. Naming overall survival, objective response, and safety outcomes does not communicate their estimates, uncertainty, denominators, missingness, or analysis methods. Those are central components of statistical interpretation, not optional details.

Finally, the safety figures demonstrate the value of reading counts alongside the design. Serious and other adverse event counts are recorded, but in a single-group study they are not comparative risk estimates. The registry's incomplete reporting of outcome estimates and analysis details leaves important questions unresolved. Statistically, this is a reminder that transparent reporting of estimates, uncertainty, populations, missing data, and planned analyses is necessary for readers to evaluate what a trial contributes.

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.

Several limitations specific to this study affect interpretation of the registry record. The single-group, non-randomized design has no concurrent control group, so it cannot directly estimate a comparative treatment effect. The trial is open-label and has no masking, as recorded in the registry. The record does not report procedures for independent outcome review or further safeguards against assessment bias.

The primary endpoint result and its 95% confidence interval are not reported. The registry also does not report numerical results for the listed secondary outcomes. As a result, the efficacy findings cannot be assessed from this record, including their magnitude and precision. The record does not report the endpoint analysis population, the number with observed assessments, or how missing observations were handled.

Other statistical details are absent: the analysis plan, hypothesis tests, multiplicity approach, interim analyses, and sample-size justification are not reported in the registry record. The study's enrollment figure should not be interpreted as the number analyzed for every outcome. The registry summary describes intended dosing and follow-up assessments, but actual treatment exposure, adherence, discontinuations, and follow-up completeness are not reported.

The safety information is also limited. The record includes counts and selected serious-event terms, but it does not report comprehensive details on event ascertainment, attribution, duration, timing, or event-specific follow-up. With no control group, the reported counts do not permit a comparative safety assessment. These reporting gaps limit what can be concluded from the registry entry without implying that unreported information was not collected.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Abraxane and Avastin as Therapy for Patients With Malignant Melanoma, a Phase II Study — NCT00462423.
• Registry record last updated 2014-01-08; status last verified 2014-01.
• Results first posted 2014-01-08.
• 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

NCT00462423 is a completed Phase II study of Abraxane and Avastin for unresectable metastatic malignant melanoma. The registry describes it as multicenter, open-label, non-randomized, and single-group, with enrollment of 50. The intended population was adults 18 years of age or older with measurable metastatic melanoma, and the treatment was described as first-line therapy.

The primary endpoint was progression-free survival at four months from first treatment, determined by RECIST 1.0 and expressed as a percentage of patients. The registry identifies a 95% confidence interval but does not report the endpoint estimate or interval. Several secondary outcome areas are listed, without numerical results in the registry record.

Safety reporting includes counts for serious and other adverse events and selected serious-event terms. No randomized comparison is available, and analysis details including missing-data handling and multiplicity methods are not reported in the registry record.