Vaccine Therapy in Treating Patients With Stage III or Stage IV Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vaccine Therapy in Treating Patients With Stage III or Stage IV Breast Cancer (NCT00304096), a non-randomized phase 1 study. The primary outcome is The Number of Participants Who Experienced Dose-limiting Adverse Events.

2. Clinical Question

The study was a phase I evaluation of vaccination in advanced breast cancer. Its stated purpose was to study side effects, while a secondary outcome concerned T-cell responses against the vaccine measured by an Elispot assay after 14 day in vitro sensitization. The registry record gives the question and outcome definitions, but does not report a result for that immune-response outcome.

This distinction matters when interpreting the record: the primary question is about dose-limiting toxicity, not tumor response or survival. The serious and other adverse-event counts listed in the record are safety information, but they do not by themselves establish the value of the primary outcome. The trial design also does not support a causal comparison between participants receiving and not receiving hormone therapy.

3. Trial Design

This was a phase I, non-randomized, parallel study sponsored by the University of Virginia. The record lists enrollment of 12 participants and status as completed. It gives a start date of 2005-12 and a primary completion date of 2007-06. Masking was listed as none.

Participants received a vaccine consisting of synthetic breast cancer peptides, tetanus toxoid and Montanide ISA-51. The registry describes two strata based on hormone therapy status. Participants in one stratum received hormone therapy; participants in the other did not. The record does not describe random assignment to these strata, and its allocation classification is non-randomized. Thus, they should not be treated as comparable randomized arms or as a vaccine group and an untreated control group.

The primary outcome was the number of participants with dose-limiting adverse events during the 30 days after administration of the last vaccine. The primary outcome description gives a safety criterion of fewer than 33% experiencing dose-limiting toxicity. A secondary outcome concerned the number of participants with T-cell responses against the vaccine, measured by Elispot assay after 14 day in vitro sensitization. The registry lists two outcome measures in total, but does not report the primary event count or a result for the immune-response measure.

The record identifies the trial as phase I and its stated purpose as examining side effects. That context is important: the record describes a safety and immunogenicity evaluation, rather than a randomized test of clinical benefit. Details such as the full vaccination schedule, eligibility criteria, sample-size justification and statistical analysis plan are not reported in the registry record. The trial's completion status indicates that the study is recorded as completed; it does not establish that every planned outcome was analyzed or reported.

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: 12 participants were registered to the study and 11 received vaccines. One participant was not compliant and did not receive vaccine.

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 The Number of Participants Who Experienced Dose-limiting Adverse Events, measured over 30 days post administration of last vaccine.

The primary endpoint counts participants who experienced dose-limiting adverse events within 30 days after the last vaccine administration. It is a count of people with an event, rather than a measure of event severity averaged across participants or a time-to-event summary. The stated safety criterion is fewer than 33% of patients experiencing a dose-limiting toxicity.

In general, dose-limiting toxicity is used in early-phase research to describe adverse events relevant to decisions about whether an intervention's safety profile is acceptable for further study. A defined observation window makes clear which events are considered for the endpoint. In this record, the window is 30 days after the last vaccine, but the detailed definition of what qualifies as dose-limiting is not reported in the registry record.

The primary endpoint should not be conflated with the posted serious adverse-event figures. Seriousness and dose-limiting status are different classifications: an event may be serious without meeting the protocol's dose-limiting definition, and the registry record does not state that the two categories are identical. The record names the endpoint but does not report the number of participants who met it. Consequently, the stated safety criterion cannot be evaluated from the primary outcome result in this registry record.

The record also lists an immune-response outcome based on an Elispot assay after 14 day in vitro sensitization. That is a separate secondary measure, not a substitute for the primary safety endpoint. Its result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Outcome type and event counts

The primary endpoint is a binary participant-level outcome: each participant either experienced a dose-limiting adverse event during the defined window or did not. The endpoint is reported as a number of participants, rather than as a continuous measurement. In general, binary outcomes can be summarized as event counts and denominators, with uncertainty estimates when analyses are reported. The registry record names the primary outcome but does not report its event count or an uncertainty estimate.

A count of participants with an event is not the same as a count of all event episodes. One participant could experience more than one event, but still contributes once to a participant-level endpoint if the endpoint is defined as the number of participants affected. The registry record's primary outcome title indicates a participant count; detailed event-level rules for classifying dose-limiting toxicity are not reported.

Observation window and endpoint definition

The primary outcome's observation period is 30 days after administration of the last vaccine. In general, a fixed window helps define which events count toward an endpoint and makes the timing of the assessment explicit. Interpretation still depends on a clear event definition and complete ascertainment during that window. The registry record does not report detailed criteria for a dose-limiting event or how incomplete follow-up was handled.

The stated criterion is fewer than 33% of patients experiencing dose-limiting toxicity. That criterion is a threshold for interpreting the safety outcome, not a result. Without the observed primary event count, the registry record does not permit assessment of whether the criterion was met. It also does not report an analysis comparing the observed event frequency with that threshold.

Uncertainty and confidence intervals

In general, a confidence interval describes the range of values reasonably compatible with the observed data under a specified statistical method. For a binary safety endpoint, it can help show how imprecise an event-frequency estimate may be, especially when the study is small. A confidence interval is not a guarantee that the true value lies within the interval, nor does it replace the clinical interpretation of the event definition.

No confidence interval for the primary endpoint is reported in the registry record. No inferential analysis of the primary endpoint is reported either. The fact that the registry lists an enrollment of 12 does not fill this gap: enrollment is not a substitute for an outcome count, denominator specific to an analysis, or uncertainty estimate.

Non-randomized strata

The study is classified as non-randomized and parallel, with strata defined by hormone therapy status. In general, random assignment helps balance measured and unmeasured participant characteristics between groups on average. Without randomization, group characteristics may differ for reasons related to treatment choice or clinical circumstances. Consequently, a difference in event counts between these strata would be descriptive and could not, by itself, be interpreted as an effect of hormone therapy or of vaccination.

The record does not report a statistical comparison between the strata. It lists adverse-event counts separately, but does not give an adjusted analysis or a causal estimand. The strata are therefore best read as separate descriptive groups, not as a randomized contrast.

Immunogenicity outcome

The listed secondary outcome is the number of participants with T-cell responses against the vaccine, measured by Elispot assay after 14 day in vitro sensitization. In general, an assay-based outcome reflects a laboratory measurement using a specified test and analysis rule. Interpretation depends on the response definition, assay procedures and handling of indeterminate or missing measurements. Those details, and the observed immune-response result, are not reported in the registry record.

The secondary outcome is distinct from the primary safety endpoint. A laboratory immune response does not itself establish a clinical outcome, and the registry record does not report a tumor-response or survival analysis. No conclusion about such outcomes should be drawn from an immunogenicity measure alone.

Planning and sample-size interpretation

The registry record describes planning illustrations based on a stated fraction of the observed effect, equal allocation between arms, a two-sided significance level of 0.05 and a normal approximation. In general, such calculations explore how sample size relates to a chosen effect size, significance level, power target and allocation scheme. They depend on assumptions and are not observations from participants.

These planning illustrations are not the trial's own sample-size justification; that justification is not reported in the registry record. They are also not observed power and do not supply missing evidence about the primary outcome. Because the design was non-randomized and the posted record does not report the primary result, a planning calculation should not be interpreted as proof of a treatment effect or as a substitute for an analysis.

Analysis plan and multiplicity

In general, a statistical analysis plan specifies the populations, endpoint definitions, methods for estimating effects and handling of missing data before results are examined. Prespecification can reduce ambiguity about which analyses are primary and how multiple outcomes are interpreted. The statistical analysis plan, interim analyses and multiplicity procedures are not reported in the registry record. The record lists two outcome measures and no analyses, so it does not permit assessment of whether outcomes were analyzed according to a prespecified plan.

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("Stratum 1: Received Hormonal Therapy", "Stratum 2: Had Not Received Hormonal Therapy")
n      <- c(6, 5)
events <- c(1, 0)
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  Stratum 1: Received Hormonal Therapy  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Stratum 2: Had Not Received Hormonal Therapy  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary safety outcome and a secondary T-cell response outcome. It does not report multiplicity procedures, a hierarchy for interpreting multiple outcomes, or adjustments to account for testing more than one outcome. In general, multiplicity matters when several hypotheses are tested because the chance of at least one apparently notable result can increase as the number of tests grows. No conclusion about the trial's control of this issue can be made from the registry record.

The record does not report an analysis population for either outcome. It does not specify whether the primary analysis included all enrolled participants, only participants who received a vaccine, or another defined group. The handling of participants with incomplete follow-up, missing adverse-event assessments, or missing Elispot results is also not reported in the registry record.

In general, missing outcome data can affect an estimate when the probability of missingness is related to the outcome or to participant characteristics. Methods for handling missing data should be described along with the assumptions they require. Since the registry record gives neither the extent of missingness nor its handling, the completeness of outcome ascertainment cannot be assessed from the posted information.

The registry record lists two outcome measures and zero analyses. This means the record does not present an analysis result for either listed outcome. It does not establish why those analyses are absent or whether analyses were conducted outside the registry record. The primary outcome result and the secondary immune-response result are not reported in the registry record.

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: fever (16.7%).

The posted serious adverse-event information is descriptive. In the stratum receiving hormonal therapy, 1 of 6 participants at risk had a serious adverse event; in the stratum not receiving hormonal therapy, 0 of 5 participants at risk had a serious adverse event. Fever is listed as a top serious term at 16.7%. The record separately lists other adverse-event counts of 1 of 6 and 1 of 5.

These figures should not be treated as a randomized comparison. The study was non-randomized, and the strata differ by hormone therapy status. No adjusted comparison or inferential test is reported in the registry record. The counts also should not be substituted for the primary dose-limiting toxicity outcome: the record does not say that serious adverse events and dose-limiting adverse events are equivalent categories.

In general, an adverse-event summary depends on event definitions, observation periods and completeness of reporting. The primary endpoint specifies a 30-day period after the last vaccine, while the adverse-event entries do not provide a separate timeframe in the information recorded. The relationship between the time periods and classifications is not reported in the registry record. Death counts are not reported in the adverse-event entries.

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

The registry record documents a phase I study of a synthetic-peptide vaccine in participants with advanced breast cancer, with a primary focus on dose-limiting adverse events and a secondary focus on T-cell responses. It reports some serious and other adverse-event counts by hormone-therapy stratum. These registry entries describe the study and a portion of its posted safety information.

The record does not report the primary dose-limiting adverse-event count, so the stated criterion of fewer than 33% cannot be evaluated. It also does not report the result for the T-cell response outcome. The available information therefore does not establish the frequency of dose-limiting toxicity or the frequency of immune responses. The record does not report tumor response, survival or comparative clinical outcomes.

The groups defined by hormone therapy status are not randomized control groups. Any difference in their recorded adverse-event counts should not be attributed to hormone therapy or to the vaccine. In general, non-randomized groups may differ in factors that affect outcomes, and the registry record does not report adjustment for such factors.

These findings should not be interpreted as evidence that the vaccine is beneficial or ineffective. The study's phase I purpose and the outcomes listed do not constitute a randomized assessment of clinical efficacy. In general, safety counts and laboratory immune-response measures answer different questions from clinical benefit. The registry record also lacks the primary result and key details about analysis populations, missing data and statistical methods that would be needed for a fuller assessment.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it separates a defined safety question from the limits of what a registry record can establish. The primary outcome is a participant count for dose-limiting adverse events within a specified period, and the record states a safety criterion. But without the corresponding observed count, the criterion cannot be assessed. A clearly worded endpoint is useful, yet it does not replace reporting the outcome itself.

The record also illustrates why separate adverse-event categories should not be conflated. Serious adverse-event counts are posted for the hormone-therapy strata, while the primary endpoint concerns dose-limiting adverse events. The registry record does not establish that these categories match. Preserving that distinction avoids treating one type of safety summary as a result for another endpoint.

The non-randomized design gives another important lesson. Strata based on hormone therapy status can describe what was recorded in each group, but they do not create a randomized comparison. Differences in counts may reflect underlying group differences, and the record provides no adjusted comparison. Descriptive group data can be informative without supporting causal claims.

Finally, the record lists an immunogenicity outcome as well as a safety endpoint, but does not report either analysis. This makes clear that outcome definitions, analysis plans and posted results are separate elements of evidence. Planning illustrations cannot replace observed trial results, and a completed status does not demonstrate that results are available. Transparent reporting of event definitions, denominators, missingness and analysis methods is essential for readers to judge precision and relevance.

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 interpretation is that the registry record does not report the primary dose-limiting adverse-event count, despite naming the endpoint and its assessment window. The stated criterion cannot therefore be evaluated from the record. The secondary T-cell response result is also not reported, so the immunogenicity question remains unanswered in the posted information.

The adverse-event summaries are limited to counts by hormone-therapy stratum. The design was non-randomized, and the record does not report a comparative or adjusted analysis. The strata should not be treated as controls for one another. The serious adverse-event listings are not identified as the same outcome as dose-limiting toxicity, and their relationship to the primary endpoint is not reported.

Additional details needed to assess the results are absent: the full dose-limiting event definition, outcome analysis populations, missing-data handling, confidence intervals, statistical analysis plan and multiplicity procedures are not reported in the registry record. The record also does not report the full vaccination schedule or a sample-size justification. It lists enrollment of 12, but enrollment alone does not show how many participants contributed to each outcome analysis.

The registry record does not report clinical efficacy outcomes such as tumor response or survival. Accordingly, the available information is limited to the study description and posted adverse-event summaries; it cannot support conclusions about clinical benefit or a causal effect of vaccination.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Vaccine Therapy in Treating Patients With Stage III or Stage IV Breast Cancer — NCT00304096.
• Registry record last updated 2013-04-09; status last verified 2013-02.
• Results first posted 2013-04-09.
• 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

This completed phase I study was sponsored by the University of Virginia and evaluated a vaccine made from synthetic breast cancer peptides, tetanus toxoid and Montanide ISA-51 in participants with stage III or stage IV breast cancer. The registry lists enrollment of 12, non-randomized allocation, no masking and a parallel model. It gives a start date of 2005-12 and a primary completion date of 2007-06.

The primary outcome was the number of participants with dose-limiting adverse events during the 30 days after the last vaccine, with a stated criterion of fewer than 33% experiencing dose-limiting toxicity. A secondary outcome concerned T-cell responses measured by Elispot assay after 14 day in vitro sensitization. Neither outcome result is reported in the registry record.

Posted adverse-event entries include serious-event counts of 1 of 6 and 0 of 5 across the hormone-therapy strata, and a serious term of fever at 16.7%. The non-randomized strata are descriptive, not a causal comparison. The statistical analysis plan, analysis populations and missing-data handling are not reported in the registry record.