This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Vaccine Therapy in Treating Patients With Stage IV HLA-A2 and HER2 Positive Breast or Ovarian Cancer Receiving Trastuzumab (NCT00194714), a na phase 1, phase 2 study. The primary outcome is Immune Response Measured by IFN-gamma Secreting PBMC Precursor Frequency by ELIspot and HLA-A2 Major Histocompatibility Complex Tetramer Analysis.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00194714 |
| Phase | Phase 1, Phase 2 |
| Condition | HER2/Neu Positive, HLA-A2 Positive Cells Present, Stage IV Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 22 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Washington |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with stage IV breast or ovarian cancer whose cancer was HER2-positive and who had HLA-A2-positive cells present. The registry summary describes them as receiving trastuzumab. The registry enrollment is 22; this figure is not necessarily the number contributing data to every outcome.
Intervention
Patients received a HER-2/neu peptide vaccine by intradermal injection once per month for 6 months, unless disease progression or unacceptable toxicity occurred. The study also included laboratory biomarker analysis. The registry describes booster vaccination as an approach intended to increase HER2-specific immunity and immune memory cells.
Comparator
There was no comparator arm. The design is recorded as single-group, with allocation listed as not applicable and masking listed as none. Consequently, the study does not provide a randomized, like-for-like comparison with a control group.
Primary question
The primary endpoint concerned immune response, assessed through IFN-gamma-secreting PBMC precursor frequency using ELIspot and through HLA-A2 major histocompatibility complex tetramer analysis. The outcome timeframe was up to 1.5 years, defined as 12 months following the last vaccination. The registry record does not report the primary outcome results, so the magnitude or pattern of immune response cannot be described from the posted results.
In statistical terms, this is a question about changes in an immune measure after vaccination in a selected clinical population, rather than a direct estimate of how vaccination compares with another treatment or with no vaccination. The study title and summary frame the work as an investigation of side effects and immune response. Overall survival is listed as a secondary outcome, but its results are not reported in the registry record.
The clinical context matters to interpretation: the registry describes participants as having advanced HER2-positive disease and receiving trastuzumab. It does not report enough detail to determine how treatment history, disease status, or other participant characteristics related to the immune measurements. Nor does the registry record report the eligibility details beyond the stated cancer types, stage, HER2 status, HLA-A2 status, and trastuzumab context.
3. Trial Design
This completed study is recorded as phase I/II and uses a single-group model. Allocation is listed as not applicable, and masking is listed as none. The registry enrollment is 22. That enrollment figure describes the registry record; it should not be assumed to be the denominator for every endpoint or safety measure.
The intervention was a HER-2/neu peptide vaccine, administered intradermally once per month for 6 months in the absence of disease progression or unacceptable toxicity. Laboratory biomarker analysis is also listed. The record gives no control arm, so observed changes during follow-up cannot be separated from changes that might have occurred because of the underlying disease, trastuzumab, other care, or time.
The study started in 2016-05, had a primary completion date of 2021-03-31, and is marked completed. The primary outcome timeframe is up to 1.5 years, specified as 12 months following the last vaccination. Overall survival is listed as a secondary outcome. The registry record lists 3 outcome measures, but does not report their results.
The primary endpoint is described as an immune response measured with ELIspot and HLA-A2 major histocompatibility complex tetramer analysis. The ELIspot description classifies response according to changes in spots per well relative to baseline or the previous value. The tetramer assay description concerns specific lysis in a laboratory assay. These are immune and laboratory outcomes; they are not direct measures of clinical benefit.
No statistical analysis is listed in the registry record. It does not report the analysis population, how many participants contributed to each endpoint, the handling of missing measurements, or an inferential model. A protocol-level sample-size justification, interim analyses, and a prespecified statistical plan are not reported in the registry record. Without those details, the design can be described from the registry, but its planned statistical operating characteristics cannot be reconstructed.
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
| Stage | Treatment (HER-2/Neu Peptide Vaccine) |
|---|---|
| STARTED | 22 |
| COMPLETED | 21 |
| NOT COMPLETED | 1 |
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.
| Characteristic | Unit | Treatment (HER-2/Neu Peptide Vaccine) |
|---|---|---|
| Participants analysed | 21 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 19 |
| Age, Categorical: >=65 years | Participants | 2 |
| Age, Continuous | years | 49 (33 to 76) |
| Sex: Female, Male: Female | Participants | 21 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 21 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 20 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 21 |
6. Primary Endpoint
The registry lists the primary outcome as Immune Response Measured by IFN-gamma Secreting PBMC Precursor Frequency by ELIspot and HLA-A2 Major Histocompatibility Complex Tetramer Analysis, measured over Up to 1.5 years (12 months following the last vaccination).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint combines two ways of assessing immune response to HER2-related peptides. The first is IFN-gamma-secreting PBMC precursor frequency measured by ELIspot. In the registry description, increased response is defined as spots per well greater than 2 standard deviations above baseline; a result within 2 standard deviations of the previous value is classified as unchanged; and a result greater than 2 standard deviations below the previous value is classified as decreased. The description associates two standard deviations with a P value of .05 and a 95% probability that values are statistically significant.
The second component is HLA-A2 major histocompatibility complex tetramer analysis. The registry describes a non-radioactive cell-lysis assay using an HLA-A2-transfected, HER2/neu-expressing breast cancer cell line and T cells expanded after stimulation with immunizing peptide. It describes calculating percent specific lysis from experimental, spontaneous, and maximum release measurements. This is a laboratory measure of cell killing under assay conditions, rather than a clinical outcome in the patient.
Immune assays are used in this kind of study to examine whether vaccination is accompanied by a measurable immune response. They can help characterize biological activity, but a change in an immune measure alone does not establish a change in symptoms, disease control, or survival. The stated timeframe is up to 1.5 years, or 12 months following the last vaccination. The registry record does not report primary endpoint values, participant-level response classifications, or an estimated treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies the primary outcome and describes how immune response was to be assessed, but does not report the resulting measurements. There is therefore no posted estimate of the number of participants with increased, unchanged, or decreased immune response, and no reported summary of the assay results. The direction, size, and precision of the primary outcome cannot be evaluated from the registry record.
The study has no comparator arm. Even if within-participant changes were reported, a single-group study would describe what happened during the study period, not what would have happened to comparable participants under a different treatment or without the vaccine. The absence of randomization and masking also means that the record does not support a controlled estimate of a vaccine-specific effect. This is a design limitation, not evidence for or against the biological hypothesis.
The registry enrollment is 22, while the safety record lists 21 participants at risk for each of the adverse-event categories shown. Those figures should not be treated as interchangeable denominators. The registry does not explain the difference or state how many participants contributed to each immune outcome. It would therefore be inappropriate to infer endpoint denominators from enrollment or from the safety group.
Overall survival appears among the secondary outcomes, but no survival estimate, event count tied to that endpoint, follow-up summary, or analysis is reported in the registry record. The deaths figure in the safety information does not substitute for an overall-survival analysis: the registry does not provide the timing, causes, follow-up pattern, or method needed to interpret deaths as a time-to-event outcome.
Precision cannot be assessed for the primary result because no primary result estimate or confidence interval is reported. In general, a confidence interval describes the range of values compatible with an estimate under a specified statistical method; its width conveys uncertainty. No such interval for immune response or survival is reported in the registry record. A missing estimate is not a null result and should not be described as evidence of no immune response.
The safety information lists serious adverse events in the treatment group and gives several serious-event terms with percentages. These figures are descriptive registry entries. The record does not provide a comparator, attribution assessment, event timing, or a detailed account of severity and duration for each participant. They cannot establish whether an event was caused by vaccination, trastuzumab, cancer, or another factor.
Overall, the registry supports a description of the study question, design, assay definitions, and selected safety counts. It does not support a conclusion about the magnitude or reliability of an immune response, a comparative treatment effect, or an overall-survival effect. Those conclusions would require outcome results and analysis details not reported in the registry record.
9. Statistical Methods Explained
Statistical interpretation depends on distinguishing what the study measured from what it can establish. The primary outcome is an immune-response measure assessed through ELIspot and tetramer-based laboratory analysis. The study is single-group, so the observations concern the vaccinated cohort over time. Without a comparator, an observed change would not by itself identify the vaccine as the cause. This is a general limitation of uncontrolled before-and-after evidence.
What does the ELIspot classification represent?
The registry describes response categories by comparing spots per well with baseline or the previous value. A change greater than 2 standard deviations above baseline is described as increased; a value within 2 standard deviations of the previous value is described as unchanged; and a change greater than 2 standard deviations below the previous value is described as decreased. These cutoffs turn a laboratory measurement into categories. Categorization can make results easier to describe, but it also discards information about the exact size of changes and places results on either side of a threshold into different labels.
The registry description says that two standard deviations is equivalent to a P value of .05 and that there is a 95% probability that values are statistically significant. That wording is part of the endpoint description. In general statistical usage, a significance threshold does not mean there is a 95% probability that a particular finding is true. Interpretation depends on the model and assumptions behind the test, and the registry does not report a statistical analysis of the primary outcome or a model for repeated measurements.
What does the tetramer assay measure?
The tetramer component is described as a non-radioactive assay for cell lysis. The registry specifies an HLA-A2-transfected human HER2/neu-expressing breast cancer cell line, T cells expanded after stimulation with immunizing peptide, and an effector/target ratio of 40:1. Percent specific lysis is described using experimental release, spontaneous release, and maximum release. This assesses the activity of cells under laboratory assay conditions. It should not be interpreted as a direct measurement of tumor response in a participant.
Laboratory assays can provide mechanistic information, but their results depend on assay procedures, sample availability, and measurement variability. General statistical practice would consider whether measurements were repeated, how variability was estimated, and how samples collected at different times were handled. These details, including the statistical analysis plan, are not reported in the registry record. The registry also does not report assay results or uncertainty estimates.
Why does the single-group design matter?
A randomized comparison aims to balance measured and unmeasured factors between groups, supporting a clearer comparison of outcomes. This study has no control group and no random allocation. A change from baseline, if available, could reflect the vaccine, the course of disease, trastuzumab, other care, measurement variation, or a combination of influences. This is a general issue of causal inference, not a claim about what happened in this study.
Masking is listed as none. In general, knowledge of treatment can affect care, reporting, or assessment, although the relevance depends on the outcome and how it is measured. A laboratory assay may involve less subjective judgment than a symptom assessment, but laboratory handling and endpoint classification still require methods that are clearly specified. The registry does not report further procedures for reducing measurement or assessment bias.
How should uncertainty be understood?
In general, an estimate describes the observed data, while a confidence interval communicates uncertainty around that estimate under a stated method. A narrow interval usually indicates greater precision than a wide interval, but neither interval alone establishes clinical importance or causality. The registry record does not report a primary estimate or confidence interval, so precision cannot be evaluated. It also does not report a statistical test, model, or adjusted analysis for the primary endpoint.
For repeated immune measurements, general analytical considerations include whether the analysis uses all available time points, how within-participant correlation is handled, and what happens when measurements are missing. A participant's measurements over time are not generally independent. Ignoring that dependence can misstate uncertainty. The registry does not report an analysis method for longitudinal measurements or a missing-data approach.
Over-dispersion is a general concern when count data vary more than a chosen statistical model expects. If spot counts or other count outcomes are analyzed, a model that assumes less variability than the data contain can produce uncertainty estimates that are too small. The registry record does not state whether count modeling was used, whether over-dispersion was assessed, or whether the outcome was analyzed as a count or as categories. No such method should be inferred from the endpoint description alone.
The record lists 3 outcome measures and 0 analyses. The primary outcome is defined, and overall survival is identified as a secondary outcome, but statistical procedures and outcome results are not reported in the registry record. Any planning illustrations elsewhere should be understood as hypothetical sample-size calculations based on their stated assumptions, not as observed power or as proof that the original study was adequately powered. The registry's description of such illustrations specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; those assumptions do not describe this single-group trial's design. Sample-size illustrations are planning aids, not findings from the study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures, including the primary immune-response outcome and overall survival as a secondary outcome. It reports 0 analyses. The record does not describe a multiplicity strategy, such as whether statistical testing across outcomes or time points was adjusted, prioritized, or treated as exploratory. Without that information and the outcome results, the risk of interpreting chance findings across multiple assessments cannot be evaluated.
The ELIspot endpoint involves response classifications and a stated observation period extending up to 1.5 years. The registry does not report how many time points were analyzed, whether comparisons were made at particular visits, or how repeated measurements were summarized. These choices can affect interpretation, especially when measurements are available at multiple times. The analysis plan is not reported in the registry record.
Missing-data handling and analysis populations are also not reported. The registry does not state how many participants had evaluable baseline and follow-up immune measurements, how missing samples or visits were handled, or whether participants were analyzed according to a prespecified population. The enrollment of 22 should not be assumed to be the denominator for each outcome. The safety record separately lists 21 participants at risk, and the registry does not explain the relation between those figures.
In general, missing measurements can affect both the number of observations available and the interpretation of change over time. If missingness is related to disease progression, toxicity, or other factors, an analysis limited to available measurements may not represent the full enrolled group. This is a general methodological concern, not a statement about why data may be absent in this study. The registry record does not report the extent or reasons for missing primary outcome measurements.
No protocol-level sample-size justification, interim analysis plan, statistical analysis plan, or sensitivity analysis is reported in the registry record. Consequently, it is not possible to assess whether the analyses followed a prespecified approach or how robust any result would be to alternative assumptions. The registry does not report primary or secondary outcome estimates that could be evaluated for multiplicity or missing-data sensitivity.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Treatment (HER-2/Neu Peptide Vaccine) | 3 | 21 | 14.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (HER-2/Neu Peptide Vaccine) | 11 of 21 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Treatment (HER-2/Neu Peptide Vaccine) | 21 of 21 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment (HER-2/Neu Peptide Vaccine) |
|---|---|---|
| CNS Cerebrovascular Ischema | Nervous system disorders | 1 of 21 |
| Cardiac Arrhythmia | Cardiac disorders | 1 of 21 |
| Ulceration | Skin and subcutaneous tissue disorders | 1 of 21 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (HER-2/Neu Peptide Vaccine) |
|---|---|---|
| Fatigue | General disorders | 20 of 21 |
| Injection Site Reaction | General disorders | 20 of 21 |
| Pain - Headache | Nervous system disorders | 14 of 21 |
| Myalgia | Musculoskeletal and connective tissue disorders | 13 of 21 |
| Rigors/Chills | General disorders | 12 of 21 |
| Pruritis/Itching | Skin and subcutaneous tissue disorders | 12 of 21 |
| Nausea | Gastrointestinal disorders | 12 of 21 |
| Diarrhea | Gastrointestinal disorders | 11 of 21 |
| Lymphopenia | Investigations | 10 of 21 |
| Leukopenia | Investigations | 10 of 21 |
Serious events with the highest arm-level rate: cns cerebrovascular ischema (4.8%), cardiac arrhythmia (4.8%), ulceration (4.8%).
The registry safety group is Treatment (HER-2/Neu Peptide Vaccine). It lists 21 participants at risk for serious adverse events and 3 with serious adverse events. For other adverse events, it lists 21 at risk and 21 with events. Deaths are listed as 11. These are registry counts; the record does not give a detailed account of event timing, duration, severity by participant, or the relationship between adverse events and deaths.
The registry also lists CNS Cerebrovascular Ischema, Cardiac Arrhythmia, and Ulceration among the top serious adverse event terms, each with 4.8%. These are reported terms and percentages, not evidence that the vaccine caused the events. The record does not report an attribution assessment or a control group that could support a comparative safety estimate.
Safety counts need to be read with their stated group and denominator. The listed at-risk count is not the registry enrollment, and the record does not explain the difference. Counts of participants with events do not necessarily describe the number of individual event episodes. The registry does not clarify whether participants could contribute more than one event or how recurrent events were handled.
Deaths listed in the safety information should not be treated as an overall-survival result. A survival analysis requires information about follow-up and event timing, among other details. Although overall survival is listed as a secondary outcome, its results and analysis are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this completed phase I/II study evaluated a HER-2/neu peptide vaccine in a single-group population described as having stage IV HER2-positive, HLA-A2-positive breast or ovarian cancer and receiving trastuzumab. It defines an immune-response endpoint based on ELIspot and HLA-A2 major histocompatibility complex tetramer analysis. It also lists overall survival as a secondary outcome and provides selected safety counts.
Those details do not show the primary immune-response results. No number of participants with increased, unchanged, or decreased response is reported, and no assay estimate or precision measure is given. The absence of posted results is not evidence that the intervention did or did not produce an immune response. It means the registry information does not permit that conclusion.
The study design also limits what an observed change could establish. With no comparator arm, the study cannot directly estimate how outcomes differed from those under another treatment or no vaccination. In general, uncontrolled observations can describe what happened in the enrolled group, but they cannot by themselves separate treatment effects from other influences. This is particularly important in a clinical setting that includes advanced cancer and trastuzumab.
The posted safety figures describe participants with recorded events in the treatment group. They do not establish causality or comparative risk. The registry does not report enough detail to interpret the deaths as an overall-survival result, despite listing overall survival as a secondary outcome. Nor do the percentages for selected serious-event terms provide a basis for comparing safety with another treatment.
Accordingly, the record is informative about the study's question, intervention, endpoint definitions, design, and some safety reporting. It does not provide sufficient outcome data to assess the size, precision, or clinical significance of immune response, or to estimate comparative effects on survival or safety. Those are distinct questions from whether the study was completed or whether an endpoint was specified.
13. Why This Trial Matters Statistically
This study illustrates an important distinction in biostatistics: a clearly defined biological endpoint is not the same as a reported result, and a reported result is not the same as a causal treatment effect. The registry describes two laboratory approaches to immune response, including thresholds for ELIspot categories and a cell-lysis assay. Yet the primary results are not reported, so readers cannot assess the observed response or its uncertainty.
The single-group design is also statistically instructive. It can provide descriptive information about a cohort receiving the intervention, but it does not create a direct counterfactual comparison. Changes over time may have multiple explanations. Recognizing that limitation helps prevent overstatement while preserving the value of mechanistic and early-phase research questions.
The endpoint combines measurements with different interpretations. ELIspot categorization describes changes in spots per well, while tetramer analysis assesses cell lysis under laboratory conditions. Neither measurement is interchangeable with a clinical outcome. The distinction between immune activity and outcomes such as survival is central to interpreting studies that use biomarkers.
Finally, the record shows why completeness of statistical reporting matters. Without analysis methods, denominators for each endpoint, missing-data procedures, and outcome estimates, it is difficult to evaluate precision, multiplicity, or the population represented by an analysis. The study remains meaningful as a defined research effort, but its registry record does not permit a statistical assessment of the primary result.
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.
Several limitations specific to this trial constrain interpretation. First, the study is single-group, with no randomized comparator and no masking. This prevents a direct treatment comparison and leaves changes over time open to explanations other than vaccination. The registry does not report a control condition or an allocation procedure.
Second, although the primary outcome is described in detail, its results are not reported in the registry record. There are no posted response counts, assay summaries, or uncertainty estimates. The record lists 3 outcome measures and 0 analyses, limiting assessment of how the outcomes were evaluated.
Third, the registry enrollment is 22, whereas the safety group lists 21 participants at risk. The record does not explain this difference, and it does not report the denominators contributing to immune measurements or overall survival. It is therefore not possible to determine whether outcome data were available for all enrolled participants.
Fourth, the registry does not report the statistical analysis plan, sample-size justification, handling of repeated measurements, missing-data procedures, analysis populations, or multiplicity approach. The methods used to estimate uncertainty and to interpret measurements over time are consequently unclear. General statistical considerations cannot replace trial-specific reporting.
Finally, safety information is limited to selected counts and serious-event terms. The registry does not report attribution, timing, duration, or detailed participant-level event patterns. Overall survival is listed but its results are not reported. These limitations apply to the available registry record and should not be taken to mean that additional information does not exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Vaccine Therapy in Treating Patients With Stage IV HLA-A2 and HER2 Positive Breast or Ovarian Cancer Receiving Trastuzumab — NCT00194714.
- Registry record last updated 2024-06-06; status last verified 2024-05.
- Results first posted 2022-06-21.
- 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.
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18. Record Summary
NCT00194714 is a completed phase I/II, single-group study sponsored by the University of Washington. It enrolled 22 and studied HER-2/neu peptide vaccination in patients described as having stage IV HLA-A2-positive, HER2-positive breast or ovarian cancer receiving trastuzumab. The vaccine was given intradermally once per month for 6 months unless progression or unacceptable toxicity occurred.
The primary outcome was immune response assessed by IFN-gamma-secreting PBMC precursor frequency using ELIspot and HLA-A2 major histocompatibility complex tetramer analysis, over a timeframe up to 1.5 years, defined as 12 months following the last vaccination. Overall survival was listed as a secondary outcome. The registry record does not report primary or survival results, analysis methods, missing-data handling, or the statistical plan.
The safety record lists 21 at risk for serious and other adverse events, 3 with serious adverse events, 21 with other adverse events, and 11 deaths. These counts and the listed serious-event terms are descriptive and do not establish attribution or comparative risk.