Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Treatment (NCT02047253), a na phase 2 study. The primary outcome is Progression-free Survival (PFS).

2. Clinical Question

3. Trial Design

This is a completed phase 2, single-group trial sponsored by the University of Alabama at Birmingham. The registry lists enrollment of 28 and metastatic castration-resistant prostate cancer as the condition. The start is recorded as 2014-04, and primary completion as 2017-06-08. Masking is recorded as none, and allocation as NA. With no control arm, these design features describe a treatment study without a randomized comparison.

The treatment arm is named Carfilzomib. Its description specifies twice-weekly administration on consecutive days by a 30-minute intravenous infusion, on days 1, 2, 8, 9, 15, and 16, for 3 weeks every 4 weeks. Dexamethasone is described as pre-medication. The carfilzomib dose is stated as 20 mg/m2 on days 1 and 2 of cycle 1, followed by escalation in succeeding cycles; the full escalation schedule is not reported in the registry record. Acyclovir is listed as an intervention, but its purpose and dosing details are not reported in the registry record.

The primary endpoint is progression-free survival from baseline through 6 months. The registry description says Kaplan-Meier will be used and also says overall survival will continue to be monitored as a secondary objective. Listed secondary outcomes include prostate-specific antigen changes, circulating tumor cell decline over specified time points, and toxicity assessment. The record states that 8 patients did not complete treatment and were not included in the analysis. It does not provide a detailed analysis population definition, recruitment flow, or reasons for non-completion. The number enrolled should therefore not be treated as the number contributing to every endpoint.

The registry record does not report a comparator, randomization procedure, detailed eligibility criteria, or a full statistical analysis plan. The single-group design can describe outcomes in the treated group, but it cannot produce a direct randomized estimate of how outcomes would differ under another treatment or usual care.

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: 8 patients did not complete treatment and were not included in the 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.

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival (PFS), measured over Baseline through 6 months for evaluating all patients.

Progression-free survival (PFS) is the primary endpoint, with a stated timeframe from baseline through 6 months. The registry description says patient survival at 6 months will be measured and that the Kaplan-Meier method will be used. In general, PFS concerns the time until disease progression or death; however, the operational definition used in this trial—including progression criteria, assessment procedures, and the handling of deaths—is not reported in the registry record.

PFS is used in clinical research to describe how long participants remain alive without recorded disease progression. As a time-to-event outcome, it can use information from participants whose event has not occurred by the end of observation, provided censoring is defined and handled appropriately. This is a general statistical feature of the method, not evidence about the trial’s actual follow-up or censoring rules.

The record does not report a PFS estimate, event count, confidence interval, or other primary endpoint result. Therefore, the endpoint’s value and its precision cannot be assessed from the registry record. The mention of Kaplan-Meier identifies a planned method, but does not establish the size or uncertainty of the observed PFS pattern. Overall survival is described as a secondary objective; it should not be conflated with the primary PFS endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is time-to-event in form: progression-free survival is evaluated from baseline through 6 months, and the registry description names Kaplan-Meier. The record does not report a numerical PFS result, event count, confidence interval, or p-value. The method can therefore be explained, but its application cannot be checked against an estimate in the registry record.

What does Kaplan-Meier estimate?

In general, the Kaplan-Meier method estimates the probability of remaining free of the event over time. It uses the timing of observed events and accounts for participants whose observation ends before an event is recorded, under censoring assumptions. A curve or time-specific estimate is only interpretable alongside clear definitions of the event, start of follow-up, follow-up duration, and censoring rules. These implementation details are not reported in the registry record. The endpoint description says the study will measure survival at 6 months, but does not provide a numerical estimate at that time.

In general, a confidence interval describes the uncertainty around an estimated quantity. Its width depends on the data and method, and it is not a guarantee that the true value lies inside the interval. No confidence interval for PFS is reported in the registry record. Without an estimate and its uncertainty, readers cannot judge whether a reported pattern is precise or highly uncertain.

What does the single-group design allow?

The design has one treatment group and no randomized comparator. Descriptive methods can characterize outcomes within that group, but they cannot isolate a treatment contrast. In a randomized comparison, allocation helps balance measured and unmeasured prognostic factors on average; that mechanism is not present in this single-group design. This is a general design distinction, not a claim that the trial’s participants were or were not comparable to another population.

The trial is recorded as unmasked. Because the registry gives no control group, masking status does not create a comparative estimate. For outcomes that involve clinical assessment, the absence of masking can be relevant in general, but the registry record does not describe outcome-assessment procedures or establish whether the endpoint was assessed in a way that could be influenced by knowledge of treatment.

What do the reported participant counts mean?

The registry reports enrollment of 28 and states that 8 patients did not complete treatment and were not included in the analysis. These are different pieces of information: enrollment describes the study’s recorded entry count, while the exclusion statement describes an analysis-population issue. The record does not report the endpoint-specific denominator, reasons for non-completion, or whether participants with incomplete treatment had follow-up data included in any other analyses. It is not appropriate to infer an analysis count by subtracting the two figures.

In general, missing outcome data can affect estimates if the chance of missingness is related to prognosis or to the outcome itself. Statistical approaches may include explicit censoring rules, imputation, sensitivity analyses, or other prespecified procedures. The registry record does not report which, if any, were used. For a time-to-event analysis, the circumstances and timing of censoring matter; those details are not reported either.

How should planning calculations be read?

The registry’s planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also states that the effect to detect is a stated fraction of the observed effect. Those are assumptions for hypothetical planning calculations, not a description of the actual single-group design. The registry record does not report that the trial randomized participants between two arms, and those hypothetical assumptions do not turn this study into a controlled comparison.

Planning sample sizes are not observed power. In general, observed power is not a replacement for reporting an effect estimate and its uncertainty; calculations based on an observed effect may simply restate what that estimate implies under chosen assumptions. The record does not report the trial’s own sample-size justification. Because no primary endpoint estimate is reported, the basis and interpretation of any effect-based planning illustration cannot be independently assessed from the registry record.

What is not available for checking?

A complete statistical analysis plan would clarify the endpoint definition, analysis population, censoring, handling of missing data, model choices, and any planned sensitivity analyses. Those details are not reported in the registry record. The record lists 5 outcome measures and 0 analyses, but does not explain whether this reflects the full analysis history or the extent of results entered in the registry. The absence of reported inferential results means that assumptions, model fit, and robustness cannot be evaluated from the registry entries alone.

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("Carfilzomib")
n      <- c(20)
events <- c(1)
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  Carfilzomib  20  1  5.0  0.1  24.9  0.9  23.6  1.2  23.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures, including PFS as the primary endpoint and secondary outcomes concerning PSA changes, circulating tumor cell decline, and toxicity. It does not report a multiplicity strategy, such as how interpretation would account for examining more than one outcome or more than one analysis. Without such a plan, the chance of at least one apparently notable result across multiple assessments cannot be evaluated from the registry record. This is a general concern in studies with multiple outcomes; it does not imply that any particular result is false.

The registry record reports 0 analyses. It does not provide the primary endpoint result or describe a hierarchy for interpreting secondary outcomes. The record also does not state whether additional analyses were conducted but not entered. Therefore, no conclusion can be drawn about how multiplicity was handled in practice.

For missingness and analysis populations, the record says that 8 patients did not complete treatment and were not included in the analysis. It does not report why they did not complete treatment, which outcomes were available for them, or whether the analysis followed an intention-to-treat, per-protocol, or other defined population. The detailed denominator for the primary endpoint is not reported in the registry record.

In general, exclusion of participants can affect an estimate when inclusion is related to prognosis or outcome. Time-to-event analyses also require clear rules about incomplete follow-up and censoring. The registry record does not report imputation, sensitivity analyses, censoring rules, or other methods for addressing missing data. These omissions limit assessment of whether the analyzed participants represent the enrolled group and how robust an endpoint estimate would be.

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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: anemia (10.7%), hypertension (7.1%).

The registry lists 28 participants at risk for serious adverse events and reports 5 participants affected by serious adverse events. It lists 28 at risk for other adverse events and reports 0 affected by other adverse events. These are the registry’s event-category counts; they should not be read as a comparison between treatments, because the study is single-group and has no control arm.

The top serious adverse event terms are anemia (10.7%) and hypertension (7.1%). The registry also reports 6 deaths. The record does not provide enough detail to determine from these figures when events occurred, whether categories overlap, or whether an event was judged related to treatment. The death count should not be treated as a cause-specific count or as a substitute for a reported PFS result.

In general, adverse-event counts describe events recorded under a study’s definitions and reporting procedures. They do not by themselves establish causation, comparative risk, or the clinical importance of an event. The registry record does not report detailed event timing, duration, severity grading beyond the serious classification, or attribution. These entries should therefore be interpreted as descriptive safety information rather than proof that the intervention caused or prevented an event.

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

The registry record establishes that a phase 2, single-group study evaluated carfilzomib in metastatic castration-resistant prostate cancer following chemotherapy and androgen pathway inhibitors. Its stated primary endpoint is PFS through 6 months, with Kaplan-Meier named as the method. These details describe the study question and intended analysis, not the outcome.

The record does not report a PFS estimate, event count, confidence interval, or p-value. It therefore does not show how long participants remained free of progression or death under the endpoint definition, nor how precisely that pattern was estimated. The outcome definition and censoring rules are also not reported in the registry record. No claim about the magnitude or certainty of the primary result can be made from the available entries.

Because the trial has no comparator and is not randomized, any observed course in the study group would not establish how outcomes differ from those under another treatment. A single-group study can contribute descriptive information, but causal attribution requires caution. Differences from an external group could arise from participant selection, disease features, follow-up, or other factors in addition to treatment; this is a general limitation of uncontrolled comparisons.

The registry reports that 8 patients did not complete treatment and were not included in the analysis, but does not explain why or describe how missing outcomes were handled. It also lists safety counts, including 5 participants with serious adverse events and 6 deaths, without reporting causal attribution in the entries described. Those counts should be kept distinct from efficacy results and should not be interpreted as proof of treatment-related harm or benefit.

Accordingly, the record supports a description of the design, planned primary endpoint, and selected safety information. It does not support a quantitative conclusion about PFS, a comparison with another treatment, or a definitive causal interpretation. The absence of a reported endpoint estimate is a substantive limitation, not evidence that the endpoint had a particular value.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly named time-to-event endpoint and the absence of a reported endpoint result. The registry identifies PFS, a 6-month timeframe, and Kaplan-Meier as the planned method. Those elements indicate what the investigators intended to assess, but readers also need the estimate, uncertainty, and event information to judge the observed data. Those results are not reported in the registry record.

The single-group design also defines the limits of interpretation. It can describe outcomes in the treated group, but it cannot estimate a randomized contrast with another therapy or control condition. That distinction matters when a study is discussed in the context of treatment effects: a within-group observation is not equivalent to evidence that the intervention caused the observed outcome.

The record’s participant accounting raises another statistical consideration. Enrollment is listed as 28, while 8 patients who did not complete treatment were not included in the analysis. Without an endpoint-specific analysis population and reasons for non-completion, readers cannot evaluate how those exclusions may affect an outcome estimate. Missingness and analysis-population definitions are central to assessing potential bias.

Finally, the reported serious adverse event counts and terms are descriptive, and the registry does not give event attribution or timing in the entries described. The planning illustration uses hypothetical assumptions that include equal allocation between two arms, despite the registered design being single-group; such planning is not observed power and is not a substitute for the trial’s result. Together, these features illustrate why design, analysis population, uncertainty, and reporting completeness must be considered alongside the name of an endpoint.

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 is that the registry record does not report a primary PFS estimate or its uncertainty. Although the endpoint and planned Kaplan-Meier method are identified, the event count, confidence interval, and p-value are not reported. The endpoint definition, progression criteria, follow-up procedures, and censoring rules are not reported either. As a result, the primary outcome cannot be independently evaluated.

The study is single-group, with allocation recorded as NA and no masking. Without a randomized comparator, any outcomes cannot establish a treatment contrast. This limits causal interpretation and makes it difficult to distinguish an intervention effect from other explanations for outcomes in the study group.

The record reports enrollment of 28 and says that 8 patients did not complete treatment and were not included in the analysis. It does not state the reasons, endpoint-specific denominator, analysis population definition, or methods for handling missing data. These omissions prevent assessment of how exclusions and incomplete follow-up may have affected the results.

Some regimen details are incomplete: the description states that carfilzomib dose escalation occurred in succeeding cycles but does not give the full schedule. Although acyclovir is listed as an intervention, its regimen is not reported. The record also does not provide detailed eligibility criteria, baseline characteristics, or a full statistical analysis plan. It lists safety counts and top serious event terms, but detailed event timing and attribution are not reported. These limitations constrain both interpretation of efficacy and assessment of safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 2 Trial of Carfilzomib for Metastatic Castration-resistant Prostate Cancer Following Treatment — NCT02047253.
• Registry record last updated 2018-12-19; status last verified 2018-11.
• Results first posted 2018-12-19.
• 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 NCT02047253 as a completed phase 2, single-group trial sponsored by the University of Alabama at Birmingham. It lists metastatic castration-resistant prostate cancer following chemotherapy and androgen pathway inhibitors as the study context, with enrollment of 28. The recorded start is 2014-04 and primary completion is 2017-06-08.

Carfilzomib is the study intervention, with dexamethasone described as pre-medication; acyclovir is also listed. The primary endpoint is PFS through 6 months, and the registry description names Kaplan-Meier. Overall survival is described as a secondary objective. The record says that 8 patients did not complete treatment and were not included in the analysis.

No primary endpoint estimate is reported in the registry record. Safety entries include 5 participants with serious adverse events, 0 with other adverse events, 6 deaths, and anemia (10.7%) and hypertension (7.1%) among the top serious adverse event terms. The single-group design does not provide a randomized treatment comparison.