Dacarbazine and Recombinant Interferon Alfa-2b in Treating Patients With Primary Uveal Melanoma With Genetic Imbalance: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dacarbazine and Recombinant Interferon Alfa-2b in Treating Patients With Primary Uveal Melanoma With Genetic Imbalance (NCT01100528), a na phase 2 study. The primary outcome is Number of Patients With Disease-free Survival (DFS).

2. Clinical Question

This is a Phase II investigation of adjuvant therapy for patients with primary uveal melanoma and genetic imbalance. Its central statistical aim, as described in the registry, is to characterize disease-free survival over follow-up rather than estimate a treatment contrast against a concurrent control group. The clinical question is therefore descriptive and preliminary: what DFS experience is observed in the enrolled group receiving the specified sequence of treatments?

The registry lists toxicity or Grade 4 adverse events and changes in plasma biomarkers and their association with DFS as secondary outcomes. These address additional aspects of the treatment experience and biologic measurements, but the record does not provide numerical secondary-outcome results or analysis details. The clinical question should not be read as a claim that the regimen improves DFS: without a comparator and without posted DFS estimates, the registry record cannot quantify a treatment effect.

3. Trial Design

This is a Phase II, single-group study sponsored by Case Comprehensive Cancer Center. The registry reports enrollment of 38 participants and a completed status. The study start date is 2009-11-11, and the primary completion date is 2015-07-25. Allocation is listed as NA, and masking is listed as none. These features indicate that the registry does not describe a randomized or blinded comparison.

The study population is described as patients with primary uveal melanoma with genetic imbalance. The listed conditions cover ciliary body and choroid melanoma of medium/large size and small size, iris melanoma, and recurrent intraocular melanoma. The primary endpoint population is stated as all patients enrolled in the study. The record does not provide a separate analysis population definition for the secondary outcomes.

In Arm I, participants receive dacarbazine intravenously on days 1 and 29. Beginning 4 weeks after the second dacarbazine dose, participants receive recombinant interferon alfa-2b subcutaneously 3 times a week for 24 weeks, unless disease progression or unacceptable toxicity occurs. Laboratory biomarker analysis is also listed as an intervention. The registry does not report further operational details about biomarker collection or the treatment-modification rules.

The primary endpoint is the number of patients with disease-free survival, with a timeframe of 5 years from time-of-enrollment. The description defines DFS from treatment start to documented recurrence or death and says it will be summarized using Kaplan–Meier. The registry also names two secondary outcomes: toxicity or Grade 4 adverse events via CTCAE Version 3.0, and changes in plasma biomarkers and their association with DFS.

Because this is a single-group study, observed DFS and adverse-event counts describe the enrolled group under the study regimen. They do not isolate the effect of treatment from other influences. The registry record does not report a comparator, protocol-level statistical plan, sample-size justification, interim-analysis plan, or full eligibility criteria.

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: All patients enrolled in 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.

Population: All patients enrolled in study, regardless of treatment

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Disease-free Survival (DFS), measured over 5 years from time-of-enrollment.

The primary endpoint is titled Number of Patients With Disease-free Survival (DFS), and its unit is participants. The registry gives a timeframe of 5 years from time-of-enrollment. Its definition states that DFS is calculated from the date treatment starts until documented recurrence or death. Thus, either recurrence or death qualifies as an event for the endpoint, while participants without a recorded event contribute follow-up information up to the time they are last known to be free of an event.

The registry says DFS will be summarized using the Kaplan–Meier method. In general, a time-to-event endpoint preserves information about when events occur and can account for participants whose event status is not known through the entire follow-up period. It is often more informative than a simple event count when follow-up duration differs among participants. Interpretation still depends on adequate reporting of event counts, follow-up, censoring, and the estimated survival curve.

The record sets out decision thresholds: treatment would be considered relatively ineffective if underlying 2-year DFS is <60%, while the combination would be considered promising if the underlying rate is >80%. These are stated criteria, not observed results. Numerical estimates, confidence intervals, event counts for DFS, and the number of participants remaining under observation over time are not reported in the registry record. The endpoint therefore identifies the planned measure and its intended interpretation, but does not establish where the observed DFS lies relative to either threshold.

DFS is used as a measure of time without documented recurrence or death after treatment starts. It combines two kinds of events into one endpoint; the registry does not provide a breakdown of recurrence and death within the primary endpoint. This matters when describing what the estimate represents: a DFS result would not, by itself, show which event type contributed to it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies DFS as the primary endpoint and Kaplan–Meier as the method for summarizing it. The following explanation is general: time-to-event methods use both the occurrence of events and the time participants are followed. For this trial, the endpoint description defines an event as documented recurrence or death, measured from treatment start. The stated timeframe is 5 years from time-of-enrollment.

What does Kaplan–Meier summarize?

In general, the Kaplan–Meier method estimates the probability of remaining event-free over time. It updates the estimate as events occur, using the participants still under observation at each event time. Participants who have not had an event by their last recorded follow-up can contribute information until that point, even if they are not observed for the full planned period. This is commonly described as censoring. The method does not turn a participant with incomplete follow-up into an event; it uses the available follow-up under assumptions about censoring and the observation process.

For this endpoint, the event definition combines documented recurrence and death. A Kaplan–Meier DFS estimate therefore summarizes remaining free of either event, rather than separately estimating recurrence-free survival and overall survival. The registry does not report the numbers of recurrences, deaths contributing to the primary endpoint, censoring times, or the number at risk over follow-up. Those details are important for understanding the curve and the amount of information supporting estimates at later time points.

How should an estimate and its uncertainty be read?

In general, a confidence interval gives a range of values compatible with the data and the statistical method at a stated confidence level. Its width conveys precision: a wider interval indicates more uncertainty about the underlying value than a narrower interval. A point estimate alone is not enough to assess how precisely DFS has been estimated. The registry record does not report a DFS estimate, confidence interval, standard error, or p-value, so neither the magnitude nor the precision of the primary result can be evaluated from the record.

The record gives two interpretation thresholds for underlying 2-year DFS: <60% is described as relatively ineffective, and >80% as promising. In general, thresholds are most informative when paired with the observed estimate and its uncertainty. If an estimate is near a threshold, uncertainty around it can affect how confidently it should be interpreted. No estimate or interval is available in the registry record to assess the relationship to those criteria. The thresholds should not be treated as results or as proof that one category was reached.

What can the single-group design estimate?

In general, a single-group study can characterize outcomes among participants treated according to its regimen. It does not directly estimate a contrast with a concurrent control group. Without such a comparator, a DFS estimate cannot distinguish the contribution of the regimen from prognostic differences, other care, or other influences. This is a design limitation, not a flaw in the Kaplan–Meier calculation. The registry lists allocation as NA, masking as none, and the model as single group; it does not describe a randomized comparison.

The registry’s sample-size assumptions describe a planning illustration computed from the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The intended effect is a stated fraction of the observed effect. In general, a planning illustration can explore the sample size associated with a chosen effect and analysis assumptions. It is not the trial’s own design justification unless the registry explicitly says so, and that justification is not reported in the registry record. In addition, an illustration based on two-arm equal allocation does not match the recorded single-group design. Such an illustration is not observed power. It does not tell readers how likely the actual study was to detect an effect, nor does it establish the validity of the study’s design.

How do the secondary measures fit?

The listed secondary outcomes include participants with toxicity or Grade 4 adverse events via CTCAE Version 3.0 and changes in plasma biomarkers and their association with DFS. In general, toxicity counts describe recorded adverse events under a specified classification system, while biomarker analyses can describe changes in measured biological characteristics and explore relationships with outcomes. A biomarker association does not by itself demonstrate that the biomarker causes an outcome or that treatment changes DFS through that biomarker. The registry record does not give detailed analysis methods, results, or uncertainty measures for these secondary outcomes.

Over-dispersion is a general concern for count outcomes when variability exceeds what a chosen count model assumes. If that occurs, standard errors and confidence intervals from a model that ignores the extra variability may be too small. The registry does not report a count-model analysis for the outcomes in this study, so over-dispersion cannot be assessed as an actual feature of its analyses. More generally, statistical methods need to match the outcome type, follow-up structure, and study design; the registry does not provide enough analysis detail to evaluate those choices beyond its stated use of Kaplan–Meier for DFS.

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("Arm I: Dacarbazine + Recombinant Interferon Alfa-2")
n      <- c(38)
events <- c(8)
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  Arm I: Dacarbazine + Recombinant Interferon Alfa-2  38  8  21.1  9.6  37.3  11.1  36.3  11.1  36.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures: the primary DFS outcome and secondary outcomes concerning toxicity or Grade 4 adverse events and changes in plasma biomarkers and their association with DFS. It does not report a multiplicity strategy, such as whether secondary analyses were considered exploratory or whether any adjustment for multiple testing was planned. The number of analysis records is 0. This means the registry record contains no listed analysis entries; it does not establish which analyses may have been conducted outside the record.

In general, testing or estimating multiple outcomes can create additional opportunities for apparently notable findings. A prespecified hierarchy or adjustment can help clarify how to interpret multiple tests. Without an analysis plan, readers cannot determine how the investigators intended to manage that issue, which outcome analyses were planned in detail, or whether results were selected for reporting. A multiplicity plan is not reported in the registry record.

Missing-data handling is also not reported in the registry record. The DFS description names Kaplan–Meier, a method that can use follow-up up to censoring, but the record does not specify censoring rules, follow-up completeness, reasons for loss to follow-up, or sensitivity analyses. In general, censoring is not the same as an event, and interpretation depends on the assumptions used for participants whose event status is not observed through the full follow-up period.

The primary endpoint population is described as all patients enrolled in the study. The registry does not report additional analysis-population definitions, exclusions from analysis, or how incomplete outcome information was handled. It also does not report a detailed statistical analysis plan, interim analyses, or a sample-size justification. These omissions limit assessment of prespecification and the relationship between planned and reported analyses.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: constitutional symptoms - other (2.6%), coagulation - other (2.6%).

The registry reports 38 participants at risk for the serious-event category, with 2 affected, and 38 at risk for the other adverse-event category, with 38 affected. It separately reports 10 deaths. These are counts in distinct registry fields; the record does not state whether the categories overlap, whether deaths were among participants counted as affected, or how the death count relates to the primary DFS endpoint.

The top serious-event terms are Constitutional Symptoms - Other and Coagulation - Other, each reported as 2.6%. These percentages are presented as registry values. The record does not provide further event-level detail, timing, severity breakdown beyond the listed category, duration, recurrence, or attribution to treatment. The secondary outcome description refers to toxicity or Grade 4 adverse events via CTCAE Version 3.0, but the registry does not provide a complete numerical report of that outcome or explain how these particular fields relate to it.

In general, adverse-event counts describe events recorded under the study’s definitions and observation procedures. They do not by themselves establish that treatment caused an event. Nor can the counts alone describe the full safety profile without details about event definitions, follow-up, missing information, and participant-level overlap. The reported figures should therefore be read as recorded counts and terms, not as causal estimates or a comprehensive comparison with another regimen.

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

The registry establishes that a Phase II, single-group study evaluated dacarbazine followed by recombinant interferon alfa-2b in patients with primary uveal melanoma with genetic imbalance. It records enrollment of 38 participants, a DFS endpoint defined by recurrence or death, and Kaplan–Meier as the planned summary method. It also gives stated thresholds for interpreting underlying 2-year DFS and lists toxicity and biomarker outcomes.

Those design and endpoint details do not amount to a numerical finding. The registry record does not report the primary DFS estimate, its confidence interval, the number of DFS events, or a comparison against another group. It is therefore not possible to tell from the registry record whether the observed DFS was below, between, or above the stated thresholds. No treatment-effect estimate against a control is available because the recorded design has no comparator group.

The safety counts provide limited descriptive information: 2 participants are reported as affected among 38 at risk for the serious-event category, 38 among 38 for the other adverse-event category, and 10 deaths. The record does not provide enough detail to infer causality, event overlap, or the relationship of deaths to DFS. The named serious-event terms and their reported percentages also should not be interpreted as a complete safety analysis.

In general, a favorable-looking outcome within a treated group does not by itself show that the treatment caused that outcome. A concurrent comparator helps distinguish treatment-associated differences from other influences, while uncertainty measures indicate how precisely outcomes have been estimated. Neither a comparative result nor primary-outcome precision measures are reported in the registry record. The appropriate conclusion is limited to what the record documents: a regimen, a single-group design, outcome definitions, and some safety counts, without numerical DFS results.

The trial’s stated intention to assess whether the regimen is promising is not itself evidence that it met the stated criterion. Likewise, a completed status indicates the registry’s administrative status, not that a particular efficacy threshold was reached. Conclusions about efficacy, comparative benefit, or the reasons for observed outcomes are not supported by the registry information reported.

14. Why This Trial Matters Statistically

This trial illustrates why the distinction between an endpoint definition and an endpoint result matters. The registry carefully identifies DFS as the primary outcome, defines recurrence or death as events, names Kaplan–Meier as the summary method, and states interpretation thresholds for underlying 2-year DFS. Yet numerical DFS results are not reported in the registry record. Without the estimate and its uncertainty, readers cannot evaluate whether the intended criteria were reached or how precise the estimate is.

It also demonstrates the interpretive limits of a single-group design. A treated-group outcome can describe the participants’ experience, but it does not directly show how outcomes would compare under another treatment. This is particularly relevant when the study objective uses language such as promising: an outcome threshold can be a useful development criterion, but it does not create a control group or remove uncertainty about causation.

The safety fields show another statistical lesson: counts need definitions and context. The record reports separate serious-event, other adverse-event, and death counts, but does not describe overlap, timing, attribution, or the connection between the fields. Clear event-level reporting and denominators help readers understand what is counted; those details are not all available in the registry record.

Finally, the planning assumptions associated with a sample-size illustration should not be mistaken for the trial’s design rationale. The illustration describes two-sided testing at 0.05, equal allocation between two arms, and a normal approximation, whereas the registered study is single-group. This contrast shows why planning calculations must be interpreted in light of the design they assume. The registry does not report the trial’s own sample-size justification, so the illustration cannot serve as evidence that the actual enrollment was chosen to achieve a particular power.

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 principal limitation for statistical interpretation is the absence of numerical primary DFS results. The registry does not report a DFS estimate, confidence interval, event count, or follow-up summary. Therefore the stated 2-year thresholds cannot be compared with an observed result, and the precision of the endpoint cannot be judged.

The study is recorded as single group, with allocation NA and no masking. There is no like-for-like control group in the registry record. Consequently, outcomes within the treated group cannot provide a direct estimate of the difference attributable to the regimen. The record also does not report full eligibility criteria, so the boundaries of the intended population cannot be fully assessed from the listed conditions alone.

Although the endpoint timeframe is given as 5 years from time-of-enrollment, the DFS definition measures from treatment start. The registry does not provide additional details about how these time origins were operationalized or how follow-up and censoring were handled. It does not report how many participants were followed to particular time points or whether missing outcome information occurred.

The registry lists toxicity or Grade 4 adverse events via CTCAE Version 3.0 and biomarker changes associated with DFS, but does not provide detailed outcome results or analysis methods for these measures. Safety counts lack the event-level detail needed to establish overlap, timing, attribution, and relationship to the primary endpoint. The record also does not report a multiplicity plan, interim analyses, a full statistical analysis plan, or a sample-size justification.

Finally, a sample-size illustration using equal allocation between two arms and a normal approximation should not be read as the design rationale for this single-group study or as observed power. These limitations constrain what can be concluded from the registry record, even though the study status is completed and enrollment is reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dacarbazine and Recombinant Interferon Alfa-2b in Treating Patients With Primary Uveal Melanoma With Genetic Imbalance — NCT01100528.
• Registry record last updated 2019-02-26; status last verified 2019-02.
• Results first posted 2018-10-29.
• 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

NCT01100528 is a completed Phase II, single-group study sponsored by Case Comprehensive Cancer Center, with enrollment reported as 38. It evaluates dacarbazine followed by recombinant interferon alfa-2b in patients with primary uveal melanoma with genetic imbalance. The registry reports a start date of 2009-11-11 and a primary completion date of 2015-07-25.

The primary outcome is DFS, defined from treatment start to documented recurrence or death, with Kaplan–Meier named as the summary method and a timeframe of 5 years from time-of-enrollment. The record states 2-year interpretation thresholds of <60% and >80%. Secondary outcomes concern toxicity or Grade 4 adverse events and plasma biomarkers in relation to DFS. Numerical DFS results and detailed secondary-outcome analyses are not reported in the registry record.

The registry reports 2 participants affected among 38 at risk for the serious-event category, 38 affected among 38 at risk for the other adverse-event category, and 10 deaths. These counts do not establish treatment causality or a comparative safety effect.