A Study of Bevacizumab (Avastin) in Combination With Dacarbazine in Participants With Unresectable/Metastatic Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Bevacizumab (Avastin) in Combination With Dacarbazine in Participants With Unresectable/Metastatic Melanoma (NCT01164007), a na phase 2 study. The primary outcome is Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST).

2. Clinical Question

This design addresses preliminary antitumor activity and safety in the specified population. A single-group response proportion can describe the outcomes observed among participants receiving the combination, but it cannot by itself separate a treatment effect from other explanations for those outcomes. Without a concurrent control group, the study does not provide a randomized comparison of the combination against another regimen.

The registry lists a planned enrollment of 40 participants. That figure describes enrollment, not necessarily the number included in a particular outcome analysis. The primary endpoint’s stated population requires receipt of at least one dose, while the number actually meeting that definition and the number evaluable for response are not reported in the registry record.

3. Trial Design

The registry describes a Phase II, single-group study of dacarbazine and bevacizumab in unresectable or metastatic melanoma. Allocation is recorded as not applicable, and masking as none. The study is marked completed, with enrollment of 40. Its stated purpose was to assess preliminary antitumor activity and safety in participants who had not previously received chemotherapy for metastatic disease.

Participants in the combination group were to receive both drugs until disease progression, unacceptable toxicity, participant withdrawal, or physician decision to discontinue. These stopping conditions describe the planned treatment approach; the registry record does not report how many participants stopped for each reason or how long participants remained on treatment.

The primary endpoint was the percentage of participants with complete or partial response according to RECIST. Tumor assessments were scheduled at baseline, every 12 weeks on treatment, and thereafter every 3 months, over a stated timeframe extending to approximately 6 years. The record says that complete or partial responses were to be confirmed at a follow-up visit at least 4 weeks after the initial assessment.

The record also lists secondary outcomes involving response duration, progression or death after specified response states, progression, treatment discontinuation, and time to treatment failure. The listed outcome topics do not establish which measures had complete results posted or how each was analyzed. The record lists 11 outcome measures and 1 analysis, but does not report the primary response estimate in the registry record.

Because there is only one treatment group, outcomes can be described for participants receiving the combination, but there is no within-trial control arm for a direct comparative estimate. The registry record does not report a detailed statistical analysis plan, sample-size justification, interim analysis plan, or a more detailed account of randomization or allocation procedures. No randomized comparison should be inferred from the study’s Phase II designation or its listed outcomes.

The study began on 2006-06-30, and its primary completion date is listed as 2012-05-31. These registry dates and the completed status describe the study record; they do not supply the missing endpoint results or explain the timing and completeness of each participant’s assessments.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population: All participants who signed the ICF, were assigned a study identifier, and received at least one dose of study medications.

5. Baseline Characteristics

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

Population: Safety Population: All participants who signed the Informed Consent Form (ICF) and received at least one dose of study medications.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST), measured over Baseline up to approximately 6 years (assessed at Baseline, every 12 weeks on treatment, thereafter every 3 months).

The primary endpoint is the percentage of participants whose best overall response during the study was complete response or partial response under RECIST. Complete response was defined as disappearance of all target and non-target lesions with normalization of tumor markers. Partial response was defined as a decrease of at least 30% in the sum of the longest diameters of target lesions relative to baseline. Either response had to be confirmed at a follow-up visit at least 4 weeks after the initial assessment.

A response proportion is a binary outcome summarized across participants: each participant either meets the endpoint definition or does not. Such an endpoint offers a direct description of how often a specified tumor-response category was recorded in the study population. It does not, on its own, describe how long a response lasted, whether disease later progressed, or how outcomes compare with a different treatment.

The registry states that tumor assessments occurred at baseline, every 12 weeks on treatment, and thereafter every 3 months, within a timeframe of baseline up to approximately 6 years. These scheduled assessments provide the context for identifying and confirming response. The primary endpoint result itself—the number or percentage meeting the response definition—is not reported in the registry record. The record also does not report a confidence interval or other precision estimate for that result.

The endpoint population is defined as participants who signed an informed consent form, received a study identifier, and received at least one dose of study medication. The number meeting this definition and the endpoint denominator are not reported in the registry record. Therefore, the endpoint’s definition can be described, but the observed response frequency and its precision cannot be interpreted from the available registry results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level measure summarized as a percentage: whether a participant’s best overall response was complete response or partial response according to RECIST. The registry defines the response categories and states that responses required confirmation. However, it does not report the observed response count, denominator, percentage, or uncertainty estimate. No particular statistical test or model for the primary endpoint is reported in the registry record.

What does a response percentage describe?

In general, a response percentage expresses the frequency of participants meeting a defined event criterion among a specified analysis population. The criterion must be applied consistently, and the denominator must be clear. Here, the primary population is defined as participants who signed an informed consent form, received a study identifier, and received at least one dose of study medication. The record does not state the number of participants in that population or the response denominator used for an analysis.

The distinction between enrolled participants and the analysis population matters. A participant may be enrolled but not satisfy a particular endpoint population definition, and some participants may lack the assessments needed to classify response. The registry record does not report participant flow, the number with assessable tumor outcomes, or how missing assessments affected response classification. A response percentage cannot be reconstructed from enrollment alone.

Why does confirmation matter?

The registry’s RECIST description requires complete or partial response to be confirmed at a follow-up visit at least 4 weeks after the initial response assessment. Confirmation is part of the endpoint definition, not an optional statistical adjustment. It means an initial qualifying assessment by itself would not fulfill the described definition. The record does not provide participant-level assessment histories or explain how cases without a confirmatory visit were handled.

Assessments were scheduled at baseline, every 12 weeks on treatment, and thereafter every 3 months, with the overall timeframe described as baseline up to approximately 6 years. In general, scheduled measurement times affect which events can be observed and when. The registry record does not report deviations from the schedule, the rules for handling assessments outside scheduled windows, or the exact duration of follow-up for individual participants.

What would uncertainty estimates add?

In general, a confidence interval communicates the uncertainty around an estimate, given a statistical method and assumptions. A percentage with a wide interval would be less precise than one with a narrow interval, though interpretation also depends on design and context. Neither the primary response estimate nor a confidence interval is reported in the registry record. The record does not state a confidence-interval method or a hypothesis test for the primary endpoint.

A p-value, in general, summarizes how compatible data are with a specified statistical model and null hypothesis; it is not a measure of effect size or clinical importance. No primary-endpoint p-value or tested null hypothesis is reported. In a single-group study, a comparative interpretation would additionally require a prespecified reference or benchmark, and such a comparator is not described in the registry record. The absence of a reported comparative analysis means no comparative p-value should be inferred.

What does the single-group design imply?

In general, a concurrent control group helps distinguish treatment-associated outcomes from changes that might also occur without the study regimen or under another treatment. This study is recorded as single-group, with allocation not applicable and masking none. The outcome distribution among treated participants can be described, but there is no randomized within-trial contrast. The registry record does not report an external control analysis or a prespecified historical benchmark.

The record lists 11 outcome measures and 1 analysis. These counts alone do not identify the analysis methods, the hierarchy among outcomes, or whether any adjustment was made for multiple statistical tests. The primary and secondary outcome descriptions indicate what was intended to be measured, but a full statistical plan is not reported in the registry record.

How should planning assumptions be read?

In general, sample-size planning asks how many participants may be needed under assumptions about an effect, significance level, allocation, and statistical method. A planning calculation is not an observed trial result and is not observed power. The registry’s planning note describes an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it says the effect to detect is a stated fraction of the observed effect. It also distinguishes event totals for time-to-event outcomes from participants per arm for other outcomes.

Those are descriptions of planning assumptions, not evidence that this single-group study used a two-arm design. The trial itself is recorded as single-group. Numerical planning estimates are not reported in the registry record, and the record does not report the trial’s own sample-size justification. The planning note therefore cannot be used to infer an observed comparison, an achieved power, or the rationale for enrolling 40 participants.

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("Dacarbazine + Bevacizumab")
n      <- c(37)
events <- c(7)
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  Dacarbazine + Bevacizumab  37  7  18.9  8.0  35.2  9.5  34.2  9.6  34.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary response percentage and secondary measures concerning response duration, progression or death, stable disease, treatment discontinuation, and time to treatment failure. These outcomes ask different questions and may involve different time horizons or event definitions. Their listing does not show that all were analyzed, nor does it establish a hierarchy beyond the outcome identified as primary.

Multiplicity arises in general when several hypotheses or outcomes are examined: the chance of at least one apparently unusual result can increase as the number of tests grows. Statistical plans may address this through outcome hierarchy or adjustment, but no multiplicity strategy is reported in the registry record. The record lists 1 analysis, but that count does not explain which outcomes were included, what hypotheses were tested, or whether any adjustment was used.

The endpoint population is defined as participants who signed an informed consent form, received a study identifier, and received at least one dose. This is the stated Intent-to-Treat population definition for the primary endpoint. The record does not report the number in that population, the number assessed for response, or whether the analysis population differed from it. It also does not report the handling of missing tumor assessments, withdrawals, or participants without confirmatory response assessments.

Missing-data methods matter because excluding participants or assigning outcomes to participants without assessments can change an estimated response percentage. In general, the appropriate method depends on why observations are missing and on the analysis objective. No imputation method, censoring rule, sensitivity analysis, or missing-data assumption is reported in the registry record. The actual effect of missing data on the primary result therefore cannot be evaluated.

The record also does not report interim analyses, stopping boundaries, or a detailed statistical analysis plan. These matters should be treated as not reported in the registry record rather than inferred from the Phase II label, study completion status, or list of outcomes.

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: pyrexia (2.7%), cardiac failure (2.7%), pericardial effusion (2.7%), pleural effusion (2.7%), femur fracture (2.7%).

The registry lists 37 participants at risk for serious adverse events and 5 affected by serious adverse events in the dacarbazine-plus-bevacizumab group. It lists 37 at risk for other adverse events and 32 affected by other adverse events. These are registry safety counts; the record does not provide additional detail about event severity beyond the serious-event category, timing, duration, or the number of events per participant.

The listed serious adverse-event terms are pyrexia, cardiac failure, pericardial effusion, pleural effusion, femur fracture, and drug hypersensitivity, each reported at 2.7%. A term-specific percentage is not necessarily a count of unique participants across all terms: one participant may have had more than one event. The record does not clarify overlap among these terms, so they should not be added together.

The deaths field is null; deaths are not reported in the registry record. The safety figures do not establish causality. An adverse event occurring during a study is not, by that fact alone, evidence that a study drug caused it. The registry record does not provide enough information to assess comparative safety, because there is no control group and no treatment-attribution analysis is described.

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

The record establishes that a Phase II, single-group study was designed to assess preliminary antitumor activity and safety for dacarbazine combined with bevacizumab in participants with unresectable or metastatic melanoma who had not previously received chemotherapy for metastatic disease. It defines a primary endpoint based on confirmed complete or partial response under RECIST and lists additional response, progression, and treatment-related outcomes.

The primary response result is not reported in the registry record. There is no observed response count or percentage, no endpoint denominator, and no confidence interval in the registry record. Consequently, the record does not permit a numerical statement about how often participants achieved the primary endpoint or how precisely that frequency was estimated.

The safety record includes counts of participants affected by serious and other adverse events and a list of serious-event terms with reported percentages. These data describe events recorded in the registry, but they do not demonstrate that the combination caused the events. Without a comparator group, the study also cannot provide a randomized estimate of whether the regimen differs from another treatment in response or safety.

General statistical interpretation distinguishes an observed outcome in a treatment group from a causal treatment effect. A single-group study can characterize what was recorded among participants receiving the regimen, but other factors may also contribute to outcomes. A control group and a suitable comparative design are needed to make a direct within-study comparison. The registry does not report an external comparator analysis.

The record’s completed status and planned enrollment of 40 do not fill the gap in the primary result. Enrollment is not itself a response estimate, and the stated endpoint population is defined by consent, study identification, and receipt of at least one dose. The number in that population and the number with evaluable response data are not reported in the registry record.

Accordingly, the defensible conclusion is limited: the registry records the study design, endpoint definitions, and selected safety information, while the primary outcome estimate and its precision are not reported. Neither a positive nor a negative efficacy conclusion can be drawn from an outcome value that is absent.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between an endpoint’s definition and its result. The registry gives a detailed definition of the primary RECIST response outcome, including confirmation requirements and the stated assessment schedule. Those details clarify what the study intended to count, but they cannot substitute for the observed response count, percentage, denominator, or uncertainty estimate. Because these results are not reported in the registry record, the primary statistical question remains unanswered by the available record.

The single-group design also shapes what can be learned. The study can be described as an assessment of outcomes among participants treated with dacarbazine and bevacizumab. It does not provide a randomized control group, so it cannot estimate a direct treatment contrast within the trial. This is a useful reminder that an endpoint can be clinically relevant while the design still limits causal or comparative interpretation.

Safety summaries require similar care. Counts and event-term percentages can describe what was recorded in the treated group, but they do not establish treatment causation. The absence of a control group and the lack of further details about overlap, timing, or attribution constrain interpretation. A null deaths field should not be converted into a claim that no deaths occurred; the record’s death information is not reported.

Finally, the registry’s listed planning assumptions should not be confused with evidence of the trial’s design rationale or performance. The planning note describes a two-arm illustration, whereas the study itself is recorded as single-group. Planning illustrations are not observed power and do not supply missing outcome estimates. This separation between design, planning, and observed data is central to sound statistical reading.

15. Limitations

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

The main limitation for statistical interpretation is that the primary response result is not reported in the registry record. The record defines the endpoint but gives no observed response count or percentage, denominator, or precision estimate. It is therefore not possible to assess the magnitude or uncertainty of the primary outcome from the information reported.

The single-group design means that no concurrent randomized comparison is available. Any outcome observed in participants receiving the combination would be descriptive and could not, on its own, establish the effect of the regimen relative to another treatment. Allocation is listed as not applicable and masking as none.

The enrollment figure is 40, but the number in the defined primary endpoint population and the number with evaluable response assessments are not reported in the registry record. Participant flow, withdrawal counts, follow-up completeness, and response-assessment availability are also not reported. Missing-data handling and the treatment of participants without confirmatory assessments are not reported.

Although secondary outcomes are listed, their results and analysis details are not available in the record. The statistical plan, multiplicity strategy, interim analysis procedures, and sample-size justification are not reported in the registry record. The planning note describes assumptions for an illustration, not the study’s own design rationale, and does not establish an observed comparison or achieved power.

The safety summary is limited to the listed at-risk and affected counts, serious-event terms and percentages, and a null deaths field. Further detail on attribution, event timing, overlap between event terms, and comparative safety is not reported in the registry record. These limitations restrict interpretation of both efficacy and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Bevacizumab (Avastin) in Combination With Dacarbazine in Participants With Unresectable/Metastatic Melanoma — NCT01164007.
• Registry record last updated 2017-04-21; status last verified 2017-03.
• Results first posted 2017-04-21.
• 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

The registry record describes a completed Phase II, single-group study of dacarbazine with bevacizumab in participants with unresectable or metastatic melanoma who had not previously received chemotherapy for metastatic disease. Enrollment was 40. Treatment was to continue until progression, unacceptable toxicity, withdrawal, or physician decision to discontinue.

The primary endpoint was the percentage with confirmed complete or partial response according to RECIST in the defined Intent-to-Treat population. The registry describes response definitions and assessment timing, but the observed primary response result and its precision are not reported in the registry record. Listed secondary outcomes address response duration, progression, treatment discontinuation, and treatment failure.

Safety fields list 37 participants at risk for serious and other adverse events, with 5 affected by serious adverse events and 32 affected by other adverse events. Six serious-event terms are each listed at 2.7%. Deaths are not reported in the registry record. The single-group design does not provide a randomized treatment comparison.