Naltrexone RCT for Treatment-Emergent Fatigue in Patients Receiving Radiation Therapy for Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Naltrexone RCT for Treatment-Emergent Fatigue in Patients Receiving Radiation Therapy for Breast Cancer (NCT02137252), a randomized phase 2 study. The primary outcome is Change in FACIT-fatigue Subscale Score From Randomization to End of Study.

2. Clinical Question

The registry record frames the study around treatment-emergent fatigue during radiation therapy for breast cancer. Its summary describes a rationale involving beta-endorphins and asks whether naltrexone reduces fatigue more than placebo. That rationale is background, not a clinical result from this trial. The record does not report a completed comparison of fatigue outcomes.

The stated scale runs from 0, indicating maximum fatigue, to 52, indicating minimum fatigue. It is reverse-scored, so higher scores correspond to less fatigue. The record identifies a score of 34 or less as significant cancer-related fatigue under ICD10 criteria and describes a 10-point change as clinically meaningful. Those are descriptions of the measure and its interpretation, not findings from participants in this trial.

3. Trial Design

This was a randomized, double-blind, parallel-group phase 2 trial sponsored by Dana-Farber Cancer Institute. The planned comparison was naltrexone against a sugar-pill placebo. The record lists total enrollment as 3 and trial status as terminated. It also identifies the primary-outcome population as a trial terminated early; the reason for termination is not reported in the registry record.

The treatment schedules describe daily medication for 5 weeks. Naltrexone was to begin at 25 mg/day during the first week, with escalation to 50 mg/day after one week unless significant early improvement in fatigue or adverse events precluded escalation. The placebo description gives a corresponding daily schedule. The posted text for each treatment description ends mid-sentence, so further details about the escalation conditions are not reported in the registry record.

The primary outcome is titled as change in FACIT-fatigue subscale score from randomization to the end of the study. The timeframe refers to baseline and weekly monitoring visits from the start of radiation therapy for people meeting the fatigue eligibility threshold. This describes when the measure was intended to be assessed, but does not establish that every planned assessment occurred. Completion of assessments and follow-up is not reported in the registry record.

The record does not report a sample-size justification, a planned enrollment target, the reason for stopping, or whether the allocation was balanced in practice. With enrollment of 3 and no reported outcome analyses, the registered design alone cannot show whether the treatment groups were comparable on baseline characteristics or whether the intended comparison was completed. Details such as the randomization sequence and concealment method 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.

Before assignment: In the monitoring phase, eligibility for randomization was defined as FACIT-F subscale score \>=10 pre-radiation therapy and decrease in FACIT-F of 10 points.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: trial terminated early

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 Change in FACIT-fatigue Subscale Score From Randomization to End of Study, measured over Evaluated at baseline, weekly monitoring visits from start of radiation therapy and meets fatigue eligibility threshold.

The primary endpoint is change in the FACIT-fatigue subscale score from randomization to the end of the study. This 13-item self-report scale measures fatigue and functional impairment resulting from fatigue. It is described as validated in cancer patients. The score ranges from 0, maximum fatigue, to 52, minimum fatigue, and is reverse-scored: a higher score represents less fatigue.

A change score is intended to capture how a participant’s reported fatigue differs between the starting assessment and a later assessment. Comparing change between randomized groups can help distinguish a pattern associated with the assigned intervention from changes that may occur over time in both groups. This is a general explanation of the role of a change endpoint; the registry record does not report a calculated change or a comparison between groups.

The record says that a score of 34 or less indicates significant cancer-related fatigue according to ICD10 criteria. It also notes that a change of 10 points has been shown to constitute a clinically meaningful difference on this subscale. These thresholds explain how scores may be interpreted; they do not show that participants in this trial crossed either threshold or experienced a particular change.

The timeframe refers to baseline and weekly monitoring visits from the start of radiation therapy for people meeting the fatigue eligibility threshold. The title specifies the change from randomization to end of study, but the record contains no numerical endpoint results. The number of completed assessments, the timing of each participant’s final measurement, and the handling of any missing measurements are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a randomized, double-blind, parallel-group phase 2 design. Randomization is a method for assigning participants to groups by chance. In general, it aims to reduce systematic differences between groups at the start of a study, so that outcome differences can be interpreted in relation to assigned treatment. Double blinding generally means that treatment assignment is masked for participants and specified study personnel; the exact masking procedures are not reported in the registry record. A parallel design assigns participants to one group rather than having each participant receive both treatments.

What would a treatment comparison estimate?

For a fatigue change endpoint, an analysis might summarize the change in each group and compare those summaries. The resulting treatment contrast would describe the difference in change between assigned groups under the chosen analysis method. This is a general description, not a report of an analysis conducted in this trial. The registry record does not state the analysis model, the summary measure, whether an adjusted analysis was planned, or how the treatment contrast was to be calculated.

For an outcome estimate to be interpretable, its definition and uncertainty matter. A point estimate gives the result under a particular analysis; a confidence interval communicates the precision of that estimate. In general, an interval reflects both the observed data and assumptions of the statistical method. No point estimate, confidence interval, or p-value is reported for the primary fatigue outcome. The record lists zero analyses, so there is no numerical efficacy result to explain.

Why the endpoint scale matters

The FACIT-fatigue subscale is a 13-item self-report measure of fatigue and functional impairment due to fatigue. It is reverse-scored, with values toward 52 representing less fatigue and values toward 0 representing more fatigue. This direction is important when interpreting change: a score increase corresponds to less fatigue on the stated scale, while a decrease corresponds to more fatigue. That is a general interpretation of the measure’s scoring, not a description of observed changes in this study.

The record identifies a score of 34 or less as significant cancer-related fatigue according to ICD10 criteria and describes a 10-point change as clinically meaningful. A statistical comparison and a clinical-meaning threshold answer different questions. A statistical interval concerns uncertainty in an estimate; a clinical threshold offers context for the size of a change. Neither can be applied to this trial’s participants without outcome values, and the registry record reports none.

What does early termination mean statistically?

Early termination can leave fewer participants and less outcome information than intended, which may limit precision and make planned analyses infeasible. This is a general statistical concern, not a statement about the reason for termination in this trial. The record reports status as terminated, enrollment of 3, and a primary-outcome population described as trial terminated early. It does not report why the study stopped, the intended enrollment, or whether termination followed a formal stopping rule.

When information is limited, estimates can be highly sensitive to individual observations. General statistical practice would consider the number of participants contributing to each outcome, the pattern of missing measurements, and the analysis assumptions. Those details are not reported in the registry record. It is therefore not possible to quantify how much the small enrollment affected a particular estimate, because no estimate is posted.

Why over-dispersion can matter

General: for count outcomes, over-dispersion occurs when the variability in observed counts is greater than a statistical model expects. If ignored, standard errors can be understated and confidence intervals can be too narrow. This issue is relevant to some count-data analyses, but the primary outcome is a fatigue scale score, and the registry record does not identify an analysis model or report an over-dispersion assessment. No claim can be made that this issue affected the trial’s analysis.

General: outcome distributions also matter. A model may rely on assumptions about the shape of residual variation or the relation between outcomes and predictors. Analysts can evaluate those assumptions and choose an appropriate method, but the registry record does not report a model, diagnostics, or an alternative analysis plan. With no outcome analysis posted, there is no basis to assess model fit or the robustness of a result.

What can planning calculations say?

In general, sample-size planning uses assumptions about the effect to detect, outcome variability, allocation, and a chosen error rate. A planning calculation is a hypothetical design aid, not an observed result or evidence that a study had a particular probability of success. The record does not report the trial’s own sample-size justification or assumptions. It also does not report an observed fatigue effect from which a planning illustration could be interpreted. No inference about power or design adequacy should be drawn from enrollment alone.

More broadly, a statistical method can clarify a result only when the underlying data and analysis are available. Here the registry record gives the endpoint definition, trial design, enrollment, and adverse-event counts, but no efficacy analysis. The statistical interpretation must therefore distinguish design intent from evidence: randomization and a defined scale describe how a comparison was structured, while a treatment effect requires reported outcome data and an analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity strategy, such as how statistical error would be handled across multiple outcomes, time points, or comparisons. The primary outcome entry is not reduced to one comparison because it has several categories or time points. Without a stated analysis plan, it is not possible to determine which assessment or contrast would have been designated for a single primary test, or whether any adjustment for multiple testing was intended.

In general, testing several hypotheses can increase the chance of obtaining a statistically notable result by chance. A prespecified strategy can define which comparisons are confirmatory and how to interpret additional analyses. This is general statistical context; the registry record does not report such a strategy or any tests for this trial.

Missing-data methods are not reported in the registry record. It does not give the number of participants with endpoint measurements, the amount or timing of missing data, reasons for missingness, or rules for including incomplete observations. Since enrollment was 3 and the study was terminated early, completeness is important to know, but it cannot be inferred from enrollment or trial status alone.

The record does not report analysis populations, such as whether participants were analyzed according to randomized assignment or according to treatment received. Nor does it report exclusions, adherence, or a sensitivity analysis. These omissions mean the population represented by any primary-outcome analysis cannot be established from the registry record. The record lists zero analyses, so there is no efficacy analysis population or missing-data handling to evaluate.

11. 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 non-serious adverse event terms

The adverse-event record lists 2 participants at risk in the naltrexone group and 1 in the sugar-pill group. Serious adverse events are recorded for 0 participants in each group. Other adverse events are recorded for 2 participants in the naltrexone group and 1 in the sugar-pill group. Deaths are recorded as 0 in both groups. No serious adverse-event terms are listed.

These are counts in groups with very small numbers of participants. They should be read as registry entries, not as precise estimates of how often events would occur in a larger population. The counts do not show event severity beyond the serious/non-serious classification, timing, duration, cause, or whether events led to treatment changes. Specific terms for the other adverse events are not reported in the registry record.

Descriptively comparing these counts does not establish whether one treatment is safer than the other. The record does not report a formal safety analysis or enough information to evaluate event patterns. The absence of recorded serious adverse events in these groups does not establish that serious events cannot occur.

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

The registry record documents a randomized, double-blind phase 2 comparison of daily naltrexone and a sugar-pill placebo for fatigue during radiation therapy for breast cancer. It reports enrollment of 3 and a terminated status. The primary outcome was intended to measure change in FACIT-fatigue subscale score from randomization to the end of the study. These details establish the question and design, but they do not provide a result for the question.

No numerical fatigue outcome, between-group estimate, confidence interval, or significance test is reported. The record therefore does not show whether fatigue scores increased, decreased, or stayed similar in either group, nor whether changes differed between groups. It cannot establish that naltrexone reduced fatigue, failed to reduce fatigue, or was equivalent to placebo. Those conclusions would require outcome data and an analysis that are not reported in the registry record.

The record’s scale description and meaningful-change threshold provide context for interpreting a possible result, not evidence that such a change occurred. Similarly, the rationale involving beta-endorphins in the trial summary is a proposed basis for investigating naltrexone, not a finding from this randomized comparison.

The adverse-event entries report zero serious adverse events in either group, along with other adverse events in both groups. With only 3 participants enrolled, these counts are limited observations. They cannot establish a general safety profile or resolve comparative safety.

In general, a trial result should be interpreted alongside its estimate, uncertainty, analysis population, missing-data handling, and study limitations. The registry record does not provide these efficacy-analysis details. The sound statistical reading is therefore narrow: the study was registered as a randomized comparison, ended early, and has no posted primary-outcome analysis. Any stronger claim about fatigue effects or treatment benefit would go beyond the reported results.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a completed analysis are both needed to answer a clinical research question. The registry identifies a fatigue measure, its scoring direction, its assessment timeframe, and a comparison between naltrexone and placebo. Those features make the intended question understandable. But a design description is not an estimate of treatment effect: the record reports no primary-outcome analysis.

Enrollment of 3 and early termination also emphasize the role of information size in statistical interpretation. In general, fewer observations tend to leave more uncertainty about an estimate, and individual measurements may have greater influence. Here there is no posted estimate or interval, so the degree of uncertainty cannot be quantified. The sample size does not justify treating an absent result as evidence for no difference.

The distinction between statistical and clinical interpretation is also relevant. The registry describes a 10-point change as clinically meaningful and gives a score threshold for significant fatigue. Those reference points could help readers interpret observed scores, but without scores or changes they cannot answer whether participants experienced a meaningful change.

Finally, the safety entries show why denominators and event descriptions matter. The record identifies the number at risk and counts of serious and other adverse events, but offers few details about the events themselves. These observations can be reported transparently without being overstated as a comparative safety conclusion.

Statistically, the central lesson is the boundary between evidence that a study was designed to generate and evidence it actually reports. The registry describes the former, while the absence of outcome analyses prevents conclusions about the primary fatigue question.

14. 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 trial-specific limitation is that the registry record reports no primary-outcome analysis. There is no numerical change in FACIT-fatigue score, group comparison, confidence interval, or significance test. The intended endpoint is therefore not available for statistical interpretation.

The trial was terminated, enrolled 3 participants, and is described as terminated early in the primary-outcome population. The reason for termination and the intended enrollment are not reported in the registry record. It is not possible to tell whether the planned assessment schedule was completed or whether the available participants had end-of-study measurements.

Baseline participant characteristics, treatment adherence, actual exposure, and allocation details are not reported in the registry record. These omissions limit assessment of group comparability and of how the planned intervention was implemented. The treatment descriptions also end mid-sentence, leaving further schedule conditions unclear.

The record does not report an analysis plan, the population used for analysis, missing-data methods, or a multiplicity strategy. It also does not report outcome distributions or participant-level data. As a result, no independent check of the endpoint analysis, model assumptions, or sensitivity to missing observations is possible from the registry information.

Safety reporting is limited to small counts and does not identify the non-serious event terms, event timing, or severity details. These constraints mean that neither the fatigue result nor comparative safety can be characterized fully from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Naltrexone RCT for Treatment-Emergent Fatigue in Patients Receiving Radiation Therapy for Breast Cancer — NCT02137252.
• Registry record last updated 2021-11-16; status last verified 2021-11.
• Results first posted 2021-11-16.
• 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.

18. Record Summary

NCT02137252 is a randomized, double-blind, parallel-group phase 2 trial sponsored by Dana-Farber Cancer Institute. It compared daily naltrexone with a sugar-pill placebo for treatment-emergent fatigue during radiation therapy for breast cancer. The stated primary endpoint was change in FACIT-fatigue subscale score from randomization to the end of the study.

The record lists enrollment of 3 and status as terminated. It describes the primary-outcome population as a trial terminated early, but the reason for termination is not reported in the registry record. Zero outcome analyses are listed, and no numerical fatigue results are reported.

For safety, serious adverse events and deaths are recorded as 0 in both groups. Other adverse events are recorded for 2 participants in the naltrexone group and 1 in the sugar-pill group. The record does not list serious adverse-event terms.