Phase II of Naltrexone in Hormone-Refractory Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II of Naltrexone in Hormone-Refractory Metastatic Breast Cancer (NCT00379197), a na phase 2 study. The primary outcome is Disease Response.

2. Clinical Question

The study asks whether a specified PET imaging change was observed during naltrexone treatment in this population. It is a question about a threshold-defined imaging outcome, not a direct comparison of naltrexone with another treatment. The study description also includes PET scans after cycle 1 and cycle 2, while the primary outcome timeframe is Week 4. The record does not report the primary outcome count, an estimate of the response rate, or an uncertainty interval. Consequently, the question can be described from the planned endpoint, but the posted results do not establish how many participants met it.

3. Trial Design

This is a phase II, single-group study sponsored by Masonic Cancer Center, University of Minnesota. The registry lists 13 participants as enrolled, allocation as NA, and masking as none. Its status is terminated. The listed start was 2006-07, and primary completion was 2013-05. A reason for termination is not reported in the registry record.

The intervention is naltrexone. The arm description specifies oral naltrexone 50 mg once a day throughout a 28 day treatment course, designated cycle 1, followed by another identical 28 day course, designated cycle 2. PET scans were planned after each cycle. The registry also lists PET scan as a procedure. This description records the planned treatment and assessment schedule; it does not establish how many participants completed each course or scan.

Because the model is single group and allocation is NA, there is no concurrent control arm against which to compare outcomes. The record does not describe random assignment, and masking is listed as none. These design features mean that any outcome observed during treatment would describe the treated group, rather than estimate a randomized difference between treatments. The registry does not report the protocol details behind the termination, treatment adherence, or the number included in each outcome analysis. Those details are not reported in the registry record.

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 Disease Response, measured over Week 4.

The primary endpoint is Disease Response, recorded as a number of participants, with a timeframe of Week 4. A participant meets the registry definition if PET imaging shows a decrease in FDG uptake (SUV) of 50% or greater in at least one metastatic site at the end of 4 weeks of treatment compared with baseline. The endpoint therefore turns an imaging change into a participant count using a prespecified threshold in the outcome description.

Imaging measures can provide a way to assess change at tumor sites, and a threshold can make the endpoint easier to classify consistently. As a general statistical point, converting a continuous measurement into a yes-or-no classification discards detail about the size of changes on either side of the threshold. Participants with changes that differ in magnitude may be grouped together if they satisfy the same threshold, while values near the cutoff may be classified differently despite being close. This is a general feature of threshold-based outcomes, not a finding about these participants.

The registry record defines how the primary outcome was to be assessed, but it does not report the number meeting the definition. It also does not report an estimated response proportion or its precision. The endpoint’s definition alone cannot establish the observed result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is defined? The primary endpoint is a binary participant-level outcome: each participant either meets the PET-based response definition or does not. The registry describes the endpoint as a number of participants, rather than as a continuous average change in FDG uptake. This distinction matters because a count answers how many participants crossed the stated threshold; it does not show the full range or distribution of imaging changes.

As a general statistical explanation, binary outcomes are often summarized by the number meeting the definition and the number assessed. A proportion can describe the share meeting the definition, while an interval estimate can express uncertainty around that proportion. Neither the primary outcome count nor an estimate of its precision is reported in the registry record, so these summaries cannot be interpreted for this trial from the record. No new estimate can be reconstructed from the enrollment figure alone.

What does a confidence interval mean? In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical method. Its width reflects precision: less information or greater variability can produce a wider interval. An interval does not guarantee that the true value lies within its particular endpoints, and it does not by itself determine whether a result is clinically important. No confidence interval for the primary outcome is reported in the registry record.

What does the design allow? The study is listed as single group, with allocation NA and masking none. A one-group result can describe outcomes among participants who received the intervention, if those results are reported. It cannot supply the randomized between-group contrast that would separate treatment effects from other explanations for change over time. Comparisons with baseline may be part of an outcome definition, but a baseline comparison is not the same as a concurrent control group.

The registry lists a phase II study, but the sample-size justification and statistical analysis plan are not reported in the registry record. The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are planning assumptions for illustrations, not evidence that the trial used a two-arm design; the registry describes this trial as single group. The record does not report the protocol’s own sample-size justification or actual inferential procedure.

Any sample-size figures in planning illustrations are planning quantities, not observed power. The stated approach uses the observed effect as a reference and considers specified portions of that effect. Because the primary endpoint result is not reported in the registry record, the observed effect used for such an illustration cannot be checked against a reported trial result. The illustrations do not demonstrate that the study had a particular probability of detecting an effect, nor do they change the number enrolled.

The planning description distinguishes time-to-event calculations, which are expressed as total events using a Schoenfeld approach, from other calculations, which are expressed as participants per arm. The secondary outcome is listed as Median Time to Event. However, the registry does not report a time-to-event result, an event count for that outcome, or an analysis of it. The planning conventions should not be mistaken for observed outcome data.

Why can over-dispersion matter? As a general concept, over-dispersion occurs when outcome variability exceeds what a chosen statistical model expects. If a model assumes less variability than is present, its uncertainty estimates can be too small and its inferences too confident. This trial’s primary outcome is a binary participant count, and no fitted model or dispersion estimate is reported in the registry record. Over-dispersion is therefore a general modeling consideration, not a reported finding from this study.

What can be concluded from no listed analysis? The registry lists 0 analyses. This means the registry record does not provide an analysis result to evaluate. It does not establish which analyses may have been conducted outside the registry, and it does not justify filling in unreported estimates. The statistical interpretation must remain limited to the design, endpoint definition, enrollment, and safety counts that are actually reported.

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("Naltrexone Treatment")
n      <- c(8)
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  Naltrexone Treatment  8  1  12.5  0.3  52.7  2.2  47.1  2.8  48.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: the primary Disease Response endpoint and the secondary outcome Median Time to Event. Multiple outcomes can create a multiplicity issue when several hypotheses are tested, because the chance of at least one apparently notable finding can rise as more tests are considered. As a general statistical approach, a study may specify a primary outcome, prespecify a testing sequence, or use an adjustment. The registry record does not report a multiplicity strategy, a testing hierarchy, or an adjustment for multiple comparisons.

The record lists 0 analyses and does not provide results for either outcome. It therefore does not report which outcomes were analyzed, whether any tests were conducted, or whether a multiplicity correction was applied. No inference about statistical significance or selective reporting can be made from the outcome list alone.

Handling of missing data is not reported in the registry record. In particular, the record does not describe whether missing PET assessments were excluded, imputed, or handled by another method. It does not report the number of participants with an evaluable Week 4 scan or the number with missing endpoint measurements. Because the primary outcome is based on imaging, the availability and handling of scans would be relevant to interpreting a response count, but those details are not reported.

The analysis populations are also not reported in the registry record. The enrollment count is 13, while the listed safety denominators are 8. The record does not explain the relationship between those counts, and the safety denominators should not be assumed to be the primary endpoint analysis population. The number of participants included in the primary or secondary outcome analyses is not reported.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists the Naltrexone Treatment group with 8 participants at risk for serious adverse events and 0 affected. For other adverse events, it lists 8 participants at risk and 4 affected. These are the reported participant counts for the respective categories. The registry does not provide additional details about the nature, timing, or severity of the other adverse events in this record.

The record lists no serious adverse-event terms. It does not report a death count; the deaths entry is not reported in the registry record. The safety denominator of 8 is distinct from the enrollment count of 13, and the reason for that difference is not reported. These counts should not be treated as if they describe all enrolled participants unless the registry record establishes that population, which it does not.

As a general point, a zero count in a small observed group does not establish that an event cannot occur. Safety counts describe what was recorded among the listed participants and depend on the scope and completeness of reporting. They do not, by themselves, provide a comparative safety estimate because this study has no separate comparator group.

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

The result that can be read from the registry is mainly a design description: a phase II, single-group study of naltrexone in hormone-refractory metastatic breast cancer, with 13 participants enrolled and a PET-based primary endpoint defined at Week 4. The record also reports the listed safety counts. It does not report the primary endpoint count or a statistical analysis of disease response.

Because the response result is absent, the record does not show how many participants met the PET threshold. It also does not provide an estimate of the response proportion, an uncertainty interval, or a p value. Without those results, the precision of the primary endpoint cannot be assessed. The endpoint definition tells readers what would count as a response, not how often that response was observed.

Even if a response count were available, the single-group design would limit causal interpretation. A change from baseline in treated participants would not, on its own, show that naltrexone caused the change. There is no concurrent comparator group in the registry design description, and no randomized treatment contrast is reported.

The safety figures should be read just as narrowly: 0 of 8 listed participants were affected by serious adverse events, and 4 of 8 were affected by other adverse events. The registry does not report why these safety counts cover 8 participants while enrollment is 13, nor does it provide a death count. The absence of a reported primary result or analysis must not be interpreted as evidence of either benefit or lack of benefit. It means the registry record does not contain the information needed to make that assessment.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it separates a clearly described endpoint from a reported result. The registry specifies a PET-based threshold and a Week 4 timeframe, but does not give the number of participants who met the definition. Readers can identify what was intended to be measured without being able to estimate the observed outcome or its precision. An endpoint definition is not a substitute for outcome data.

The single-group design also highlights the distinction between observing change and estimating a comparative treatment effect. A within-participant baseline reference is part of the PET endpoint definition, but it does not create a control group. Without a concurrent comparator, the design cannot directly distinguish treatment-associated change from other possible influences over time.

The difference between the enrollment count and the safety denominators makes clear why analysis populations and denominators matter. The registry reports enrollment of 13 and safety groups of 8 at risk, but does not explain their relationship. Counts are meaningful only with a clear population and outcome definition; the record does not establish that the same participants contribute to every reported category.

Finally, the record lists a secondary time-to-event outcome but no analyses. This illustrates why a list of planned outcomes and a statistical plan are not enough to reproduce or interpret results. The registry does not report missing-data procedures, analysis populations, multiplicity handling, or the reason the trial was terminated. These gaps constrain what statistical conclusions can be drawn from the record, regardless of the clinical motivation for the study.

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 primary limitation for interpreting efficacy is that the registry record does not report the primary disease-response result. The outcome definition is present, but there is no count of participants meeting it, no reported estimate of precision, and no analysis result. The secondary Median Time to Event outcome is listed without a result or analysis.

The design is single group, with allocation listed as NA and masking as none. There is no concurrent comparator, so the record cannot provide a randomized comparison. The registry does not report a reason for termination, and no reason should be inferred from the status alone.

Enrollment is reported as 13, while the adverse-event groups list 8 participants at risk. The record does not explain this difference. It also does not report the primary analysis population, treatment completion, the number with evaluable imaging, or how missing measurements were handled. These omissions prevent assessment of the extent to which the outcome data, if collected, represent those enrolled.

The registry does not report a statistical analysis plan, sample-size justification, multiplicity approach, or details of the outcome analyses. The planning assumptions are not a substitute for trial-specific methods or results. Safety information is limited to the listed affected counts; serious-event terms are not listed, and deaths are not reported in the registry record. These limitations restrict interpretation to the design and counts explicitly recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II of Naltrexone in Hormone-Refractory Metastatic Breast Cancer — NCT00379197.
• Registry record last updated 2017-12-28; status last verified 2017-12.
• Results first posted 2017-05-19.
• 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 describes NCT00379197, “Phase II of Naltrexone in Hormone-Refractory Metastatic Breast Cancer,” as a phase II, single-group study sponsored by Masonic Cancer Center, University of Minnesota. It lists 13 participants enrolled, status terminated, a start of 2006-07, and primary completion of 2013-05. The intervention description specifies oral naltrexone 50 mg once a day for cycle 1 and an identical cycle 2, each a 28 day course, with PET scans after each cycle.

The primary outcome is a Week 4 participant count based on a PET decrease in FDG uptake (SUV) of 50% or greater in at least one metastatic site compared with baseline. The result and statistical analyses are not reported in the registry record. The safety listing reports 0 of 8 participants affected by serious adverse events and 4 of 8 affected by other adverse events. The reason for termination, analysis populations, and missing-data methods are not reported.