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 Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for the Treatment of HER-2/Neu-Overexpressing Metastatic Breast Cancer (NCT00399529), a na phase 2 study. The primary outcome is Number of Participants With Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00399529 |
| Phase | Phase 2 |
| Condition | Breast Neoplasms |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 22 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
| Results posted | Yes |
2. Clinical Question
Population
Patients with Stage IV HER-2/neu-overexpressing metastatic breast cancer were the intended population. The registry describes the condition as breast neoplasms and frames the study as a feasibility study. It records enrollment of 22, while its brief summary describes a recruitment aim of up to 40 people to identify 20 eligible research subjects. These figures describe different aspects of the record and should not be treated as interchangeable measures of who received treatment.
Intervention
The study combined trastuzumab and cyclophosphamide with an allogeneic GM-CSF-secreting breast tumor vaccine. The vaccine was made from two irradiated allogeneic mammary carcinoma cell lines genetically modified to secrete GM-CSF. The registry describes an open-label study in which this combination was given as the study treatment.
Comparator
There was no separate control group. The registry identifies a single-group model and no allocation. Consequently, the record does not support a like-for-like comparison of the combination against a different treatment, placebo, or usual care.
Primary question
The primary outcome was the number of participants with adverse events related to study drug. The timeframe ran from the first dose through 30 days after the last dose, up to 9 months. The study also aimed to examine safety, clinical benefit, and vaccine bioactivity. A secondary outcome concerned participants with a delayed type hypersensitivity immunological response. The registry record does not report analysis results for these outcomes.
The study’s stated biological questions included whether cyclophosphamide could reduce the suppressive influence of regulatory T cells and whether trastuzumab could increase antigen processing and presentation. These are aims described in the registry summary, not findings established by the adverse-event counts. The design is best understood as an assessment of feasibility and outcomes in a treated group, rather than as a test of comparative effectiveness.
3. Trial Design
This was a Phase 2 feasibility study registered as NCT00399529. The registry lists the study as completed, with a start date of 2006-09 and primary completion in 2010-02. Its model is single group, allocation is listed as NA, and masking is listed as none. The record therefore describes an open-label study without a randomized comparator.
The treatment combined trastuzumab, cyclophosphamide, and an allogeneic GM-CSF-secreting breast cancer vaccine. The vaccine consisted of two irradiated allogeneic mammary carcinoma cell lines genetically modified to secrete human GM-CSF. The arm description includes details of the vaccine mixture and says it was given intradermally, but the administration schedule is truncated in the registry record. The full schedule and other treatment details are not reported in the registry record.
The registry records enrollment of 22. Separately, the brief summary says the study was designed to recruit up to 40 subjects to identify 20 research subjects eligible for treatment. These statements describe the planned recruitment and the enrollment field; they do not establish that all enrolled participants received treatment or were included in every outcome assessment. The adverse-event record lists 20 participants at risk for the reported event categories.
The stated purposes included assessing safety, clinical benefit, and vaccine bioactivity in people with Stage IV HER-2/neu-overexpressing breast cancer. The primary outcome was a count of participants with adverse events related to study drug over the specified safety window. Delayed type hypersensitivity was listed as a secondary outcome. The registry record does not report a detailed statistical analysis plan, the eligibility criteria, or how analysis populations were defined. It also does not report a sample-size justification for the trial’s own design.
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 | Allo GM-CSF-secreting Vaccine, Trastuzumab, Cyclophosphamide |
|---|---|
| STARTED | 22 |
| COMPLETED | 20 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Allo GM-CSF-secreting Vaccine, Trastuzumab, Cyclophosphamide |
|---|---|
| Off Study Prior to Treatment | 2 |
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 | Allo GM-CSF-secreting Vaccine, Trastuzumab, Cyclophosphamide |
|---|---|---|
| Participants analysed | 22 | |
| Age, Continuous | years | 52 (34 to 74) |
| Sex: Female, Male: Female | Participants | 22 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 19 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 3 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| 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 | 1 |
| Race (NIH/OMB): White | Participants | 20 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events, measured over From first dose through 30 days after last dose of study drug, up to 9 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is the number of participants who experienced adverse events related to study drug. It is a participant-count endpoint: it concerns whether a participant experienced an event, rather than the total number of separate event episodes. The specified observation window begins with the first dose and extends through 30 days after the last dose, up to 9 months. This defines the period in which the safety outcome was to be assessed.
Safety endpoints are used to describe harms recorded during treatment and follow-up. A count can communicate how many participants were affected in the group being studied, but by itself it does not describe the nature, severity, duration, or recurrence of every event. Nor does a count establish that treatment caused an event. The primary endpoint description focuses on events related to study drug, while the posted adverse-event summary also categorizes events by seriousness and reports a serious-event term.
The record lists a count-based primary outcome but does not provide a separate analysis record for it. The adverse-event figures therefore should be read as the reported safety information, not as a complete account of the primary endpoint analysis. Definitions for event attribution, coding, and adjudication are not reported in the registry record. Delayed type hypersensitivity was a secondary outcome, but its result is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes one treated group and reports adverse-event counts for that group. It lists 20 participants at risk for serious adverse events, with 1 affected; it also lists 20 at risk for other adverse events, with 20 affected. Deaths are reported as 0. Urticaria appears among the top serious adverse-event terms at 5.0%. These figures describe the entries in the registry record; they do not provide a controlled estimate of the effect of treatment on adverse events.
The figures need to be kept in their categories. The serious-event count is not the same measure as the other-adverse-event count, and neither count tells how many separate event episodes occurred. The record’s primary outcome is framed as the number of participants experiencing adverse events related to study drug. The posted adverse-event grouping does not, on its own, establish that all listed events were judged related to treatment. Details about the relationship between the categories and the primary outcome are not reported in the registry record.
The single-group design limits interpretation. Without a separate comparator, the registry counts cannot distinguish events arising during the study from events that would have occurred without the combination. The data also cannot separate the contributions of the vaccine, trastuzumab, and cyclophosphamide. This is a design limitation, not a statistical adjustment that can be repaired from the reported counts.
No confidence interval, hypothesis test, or analysis estimate for the primary outcome appears in the registry record. A confidence interval, in general, expresses the uncertainty around an estimate under a specified statistical procedure. Without a reported interval or analysis, the precision of an estimated event frequency cannot be assessed from the record. No result for clinical benefit or immune response is reported either.
The figures should therefore be read as a limited descriptive safety account for the participants represented in the adverse-event record. They do not establish comparative safety, treatment efficacy, or the biological mechanisms proposed in the study rationale. The record’s completed status indicates the study is listed as completed; it does not supply missing outcome analyses or resolve the limits of the single-group design.
9. Statistical Methods Explained
A count of participants with an event is a binary outcome summarized as a count: each participant is classified according to whether the event definition was met during the specified observation period. This differs from counting every event episode. A participant with repeated events may still contribute once to a participant-level count, depending on the outcome definition. The registry states that the primary endpoint is a number of participants, but detailed event-handling rules are not reported in the registry record.
What does a single-group count tell us?
A descriptive count can show how many participants in the recorded group were affected. It does not by itself estimate what would have happened to the same participants under a different treatment. In general, a comparator helps distinguish outcomes associated with the intervention from background events and other influences. This study has no separate comparator, so its event figures are descriptive rather than a relative treatment effect.
The adverse-event listing separates serious adverse events from other adverse events. These categories should be interpreted as separate reported groupings, not combined into a new total. A serious event is classified according to seriousness criteria, whereas the other category represents a different registry grouping. The record does not provide enough detail to reconstruct event-level data, confirm overlap between groupings, or determine how each entry maps to the primary outcome’s treatment-related definition.
Why can’t the counts establish causation?
An event occurring after treatment is not necessarily caused by treatment. Causal assessment requires more than timing, and in a single-group study there is no concurrent control group to provide a direct comparison of event experience. The registry gives the study’s purpose and aggregate safety figures, but does not report detailed attribution methods, event narratives, or an adjusted analysis. Accordingly, the counts describe events recorded in the study; they do not isolate the effect of any one component of the combination.
In general, uncertainty around a participant-level event estimate can be expressed using a confidence interval. The interval depends on the estimate, the amount of information, and the method used. A narrow interval generally indicates greater precision, while a wide interval indicates more uncertainty. No confidence interval or inferential analysis for the primary outcome is reported in the registry record, so no precision estimate should be inferred from the counts alone.
What is the role of the planning assumptions?
The registry includes a description of a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that non-time-to-event calculations are expressed as participants per arm, while time-to-event calculations concern total events. The illustration is not the trial’s own design justification. This trial is recorded as single group, so an equal-allocation two-arm illustration does not describe its actual design. The registry record does not report the trial’s own sample-size justification or a detailed statistical plan.
In general, a planning calculation asks how much information might be needed to detect an assumed effect under specified design and analysis conditions. Its result depends on those assumptions. Such a calculation is not an observed result and should not be interpreted as evidence that the completed study had a particular probability of finding an effect. No sample-size justification, interim-analysis plan, or stopping rule is reported in the registry record.
How should outcome analyses be distinguished?
A statistical analysis plan would ordinarily specify the outcome definitions, analysis populations, handling of missing observations, and methods for estimation or testing. Those details are not reported in the registry record. The record also lists no analysis records for the outcomes. As a result, the available description does not establish whether outcome analyses were conducted outside the registry, how incomplete follow-up was handled, or whether any adjustments were planned.
Over-dispersion is a general concern for count data when variation exceeds what a chosen probability model expects. It can make standard errors and confidence intervals too optimistic if ignored. This primary endpoint is a participant count rather than a reported event-rate model, and no model-based analysis is posted. Over-dispersion therefore cannot be assessed from the aggregate entries in the registry record. More broadly, statistical methods should match the endpoint and design; the registry’s sparse analysis information does not justify assigning a particular model to the study.
10. Multiplicity, Missing Data and Analysis Populations
The record identifies a primary safety outcome and a secondary delayed type hypersensitivity outcome, and it reports three outcome measures in total. It does not provide analysis records for these outcomes. The methods used to analyze each outcome, or whether the outcomes were all included in the final analysis, are not reported in the registry record.
Multiplicity refers, in general, to the increased chance of a false-positive finding when multiple outcomes or statistical tests are assessed. Researchers may address this through prespecified outcome hierarchies or adjustments to statistical testing. The registry record does not report whether any multiplicity strategy was planned or used. Because no outcome analysis results are present, there is no reported set of tests for which an adjustment can be evaluated.
The registry does not describe how missing outcome observations were handled, whether follow-up was complete, or whether participants who did not receive treatment were included in an analysis population. Those details matter because incomplete observation can affect estimates, particularly when the likelihood of missingness is related to health status or treatment experience. The listed enrollment and adverse-event risk counts should not be used to infer a missing-data method or analysis population.
For the same reason, the adverse-event figures cannot be assumed to represent an intention-to-treat analysis or a per-protocol analysis. The registry record does not state which participants were included in each outcome analysis or how treatment discontinuation was handled. These omissions limit reproducibility and make it difficult to judge whether the reported counts capture the outcome in the intended population over the full specified timeframe.
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 |
|---|---|---|---|
| Allo GM-CSF-secreting Vaccine, Trastuzumab, Cyclophosphamide | 1 | 20 | 5.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Allo GM-CSF-secreting Vaccine, Trastuzumab, Cyclophosphamide | 0 of 20 |
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 |
|---|---|
| Allo GM-CSF-secreting Vaccine, Trastuzumab, Cyclophosphamide | 20 of 20 |
Most frequent serious adverse event terms
| Event term | Organ system | Allo GM-CSF-secreting Vaccine, Trastuzumab, Cyclophosphamide |
|---|---|---|
| Urticaria | Skin and subcutaneous tissue disorders | 1 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Allo GM-CSF-secreting Vaccine, Trastuzumab, Cyclophosphamide |
|---|---|---|
| Erythema at Vaccine Sites | General disorders | 20 of 20 |
| Pruritus at Vaccine Sites | General disorders | 20 of 20 |
| Pain at Vaccine Sites | General disorders | 17 of 20 |
| Fatigue | General disorders | 8 of 20 |
| Urticaria | Skin and subcutaneous tissue disorders | 7 of 20 |
| Rash at Vaccine Sites | General disorders | 7 of 20 |
| Pruritus | Skin and subcutaneous tissue disorders | 6 of 20 |
| Fever | General disorders | 5 of 20 |
| Blister at Vaccine Sites | General disorders | 5 of 20 |
| Flu-like symptoms | General disorders | 4 of 20 |
Serious events with the highest arm-level rate: urticaria (5.0%).
The registry lists 20 participants at risk for serious adverse events and 1 participant affected. It lists 20 at risk for other adverse events and 20 affected, with deaths reported as 0. Urticaria is listed among the top serious adverse-event terms at 5.0%. These are the safety figures recorded for the single treatment group.
The counts are participant-level fields and should not be read as counts of every event episode. The serious and other-event groupings are reported separately; they should not be added together, because the record does not explain whether any participants appear in both categories. The percentage attached to urticaria is reproduced as reported and should not be converted into a count or treated as a complete description of all serious events.
The primary outcome concerns adverse events related to study drug. The safety summary does not provide enough information to determine the attribution of each listed event, its duration, or its clinical course. A serious event recorded during a study does not by itself establish causation. With no control group, these figures describe the recorded experience in the treatment group and do not provide a comparative estimate of risk.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry contains aggregate safety figures for a single group treated with the vaccine, trastuzumab, and cyclophosphamide. They show 1 participant affected among 20 at risk for serious adverse events, 20 affected among 20 at risk for other adverse events, and 0 deaths. Urticaria is listed among the top serious-event terms at 5.0%. The registry does not report analysis records for the outcomes.
These data do not establish that the combination caused the events, nor do they show how the safety experience compares with another treatment. Since the study has no separate control group, the counts cannot estimate a difference between treatment strategies. The combination also prevents attribution of any observed outcome to one individual component using these group-level figures.
The study’s stated aims extended beyond safety to clinical benefit and bioactivity, including delayed type hypersensitivity. No outcome analysis results for those aims are reported in the registry record. The adverse-event figures cannot be used as evidence that the vaccine generated an immune response, changed tumor outcomes, or altered the proposed immune mechanisms.
The record’s enrollment field and the at-risk counts refer to different recorded quantities. The enrollment field is 22, while the adverse-event record lists 20 participants at risk. The registry does not explain the relationship between these figures, and they should not be treated as interchangeable. It also does not report how missing observations, withdrawals, or analysis populations were handled.
In general, a feasibility study can inform whether a treatment approach and its assessment are practicable, while larger or comparative studies may be needed to estimate treatment effects precisely. The registry record does not provide enough information to judge all feasibility outcomes or the precision of the safety estimates. Its counts are descriptive evidence about recorded events, not a definitive comparative or causal conclusion.
13. Why This Trial Matters Statistically
This trial illustrates why design and analysis must be interpreted together. A single-group study can record adverse events and describe the experience of treated participants, but it does not create a concurrent estimate of what would have happened without the combination. A count can be accurately reported while still leaving the treatment’s causal contribution uncertain.
The endpoint also demonstrates the importance of specifying what is being counted. The primary outcome concerns participants who experienced adverse events, whereas event terms may describe particular types of events. Participant counts and episode counts answer different questions. The registry gives aggregate safety fields, but does not report enough detail to reconstruct event-level patterns or the relationship between those fields and the treatment-related primary outcome.
The distinction between enrollment and participants at risk is another practical issue. The record lists enrollment of 22 and an at-risk group of 20 for each reported adverse-event category. Without an explanation of analysis populations and missing data, those figures cannot be reconciled by assumption. Transparent reporting of participant flow and endpoint-specific analysis populations would help readers understand which observations contribute to each result.
Finally, the study’s biological rationale and its outcome evidence are separate. The registry describes proposed immune mechanisms and a secondary immunological outcome, but does not report analysis results for them. This is a reminder that a plausible mechanism is a study question, not a measured finding. Statistical interpretation depends on the outcomes actually reported and the design used to evaluate them.
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 most important trial-specific limitation is the single-group, open-label design with no separate comparator. The reported adverse-event counts therefore cannot support a direct comparative estimate or isolate the effects of the vaccine, trastuzumab, or cyclophosphamide. The registry record does not report randomization, masking, or a control treatment.
The record’s primary outcome description refers to adverse events related to study drug, but the posted safety grouping does not describe how relatedness was assessed. Detailed definitions, event-level information, severity grading beyond the serious grouping, and methods for reviewing events are not reported in the registry record. The aggregate counts cannot show timing, duration, recurrence, or clinical course.
The registry lists enrollment of 22, while the adverse-event fields list 20 participants at risk. The relationship between these entries is not explained. Eligibility criteria, participant flow, treatment exposure, withdrawals, and endpoint-specific analysis populations are not reported in the registry record. The treatment schedule is also incomplete in the arm description.
No outcome analysis records are listed. The registry does not report confidence intervals, hypothesis tests, missing-data methods, multiplicity handling, or a detailed statistical analysis plan. It also does not report results for clinical benefit or delayed type hypersensitivity. These gaps limit assessment of precision, reproducibility, and the completeness of outcome reporting. The record’s completed status does not resolve these limitations.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for the Treatment of HER-2/Neu-Overexpressing Metastatic Breast Cancer — NCT00399529.
- Registry record last updated 2020-04-22; status last verified 2020-04.
- Results first posted 2020-04-13.
- 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
NCT00399529 is a completed Phase 2, open-label, single-group feasibility study of an allogeneic GM-CSF-secreting breast cancer vaccine combined with trastuzumab and cyclophosphamide for Stage IV HER-2/neu-overexpressing breast cancer. The registry records enrollment of 22 and lists no separate comparator or allocation.
The primary outcome was the number of participants with adverse events related to study drug during the period from first dose through 30 days after last dose, up to 9 months. The safety record lists 20 participants at risk and 1 affected for serious adverse events, 20 at risk and 20 affected for other adverse events, and 0 deaths. Urticaria is listed among the top serious-event terms at 5.0%.
No outcome analysis records are listed. The registry record does not report a detailed analysis plan, missing-data methods, or results for the secondary immunological outcome. The single-group design supports descriptive safety reporting but not a controlled comparison.