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 A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen (NCT00623831), a non-randomized phase 1 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events (TEAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00623831 |
| Phase | Phase 1 |
| Condition | Melanoma, Sarcoma, Gastrointestinal Stromal Tumor (GIST) |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 17 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ludwig Institute for Cancer Research |
| Results posted | Yes |
2. Clinical Question
Population
Participants had malignant tumors expressing the NY-ESO-1 antigen. The registry lists melanoma, sarcoma, gastrointestinal stromal tumor, head and neck cancer, transitional cell carcinoma, prostate cancer, ovarian carcinoma, esophageal cancer, and breast cancer. The Safety Analysis Set included subjects who received at least 1 dose of study drug. Enrollment was 17.
Intervention
The intervention was mixed bacterial vaccine (MBV), administered twice weekly. Cohort 1 began at 250 EU and escalated doses within each subject in the absence of a dose-limiting toxicity until the desired pyrogenic effect was observed. Cohort 2 received a fixed dose of 60,800 EU, identified as the pyrogenic dose level in Cohort 1.
Comparator
There was no randomized or concurrent control group. The two cohorts followed different dosing approaches, but this was not a like-for-like control comparison. Differences between cohort outcomes therefore cannot be interpreted as a controlled estimate of a dosing effect.
Primary question
The primary objective was to characterize the safety profile of MBV and identify the dose associated with the desired pyrogenic effect, defined as a body temperature of 38°C to 39.5°C. Secondary objectives concerned NY-ESO-1-specific immune responses and tumor response. The primary outcome recorded the number of participants with treatment-emergent adverse events.
3. Trial Design
This was a phase 1, open-label, multiple-dose, single-group study. The registry describes non-randomized allocation and no masking. The study enrolled 17 participants and is marked completed. Its recorded start was 2007-05 and its primary completion was 2012-05. The sponsor was Ludwig Institute for Cancer Research.
Participants were assigned to one of two dosing cohorts, not randomized treatment arms. In Cohort 1, MBV started at 250 EU (dose level 1), given twice weekly. For each subsequent administration, the dose could be escalated within the same subject if no dose-limiting toxicity had occurred. Escalation continued until the desired pyrogenic effect was observed; the maximum possible dose to be investigated was 547,000 EU (dose level 8). In Cohort 2, participants received MBV twice weekly at a fixed dose of 60,800 EU (dose level 6), described as the pyrogenic dose level determined in Cohort 1.
The primary objective was safety characterization and identification of a dose inducing the specified pyrogenic effect. The secondary objectives were to evaluate immunological effects and tumor response after vaccination. The registry lists secondary outcomes for participants with serum NY-ESO-1-specific immune responses and participants with best overall tumor response.
Because this was an open-label, single-group study without a control arm, it was designed to describe experience with MBV rather than to estimate a comparative treatment effect. The cohorts also differed in dosing strategy, and cohort membership was not randomized. The registry record does not report a protocol rationale for cohort size or a detailed statistical analysis plan.
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 | Cohort 1 | Cohort 2 |
|---|---|---|
| STARTED | 13 | 4 |
| COMPLETED | 12 | 3 |
| NOT COMPLETED | 1 | 1 |
Reasons for not completing this period:
| Reason | Cohort 1 | Cohort 2 |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
| Progressive Disease | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The Safety Analysis Set comprises all subjects who received at least 1 dose of study drug.
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.
Population: All Enrolled Subjects
| Characteristic | Unit | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|---|
| Participants analysed | 13 | 4 | 17 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 8 | 3 | 11 |
| Age, Categorical: >=65 years | Participants | 5 | 1 | 6 |
| Age, Continuous | years | 58.0 (SD 11.7) | 55.5 (SD 11.3) | 57.4 (SD 11.6) |
| Sex: Female, Male: Female | Participants | 6 | 2 | 8 |
| Sex: Female, Male: Male | Participants | 7 | 2 | 9 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 9 | 4 | 13 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 4 | 0 | 4 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 13 | 4 | 17 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: Germany | Participants | 13 | 4 | 17 |
| Diagnosis at Study Entry: Melanoma | Participants | 7 | 2 | 9 |
| Diagnosis at Study Entry: Sarcoma | Participants | 2 | 1 | 3 |
| Diagnosis at Study Entry: Prostate cancer | Participants | 2 | 0 | 2 |
| Diagnosis at Study Entry: Head and neck cancer | Participants | 1 | 0 | 1 |
| Diagnosis at Study Entry: Breast cancer | Participants | 0 | 1 | 1 |
| Diagnosis at Study Entry: Transitional cell carcinoma | Participants | 1 | 0 | 1 |
| Stage IV Disease at Study Entry | Participants | 13 | 4 | 17 |
| Baseline Karnofsky Performance Status: 70% | Participants | 2 | 0 | 2 |
| Baseline Karnofsky Performance Status: 80% | Participants | 4 | 0 | 4 |
| Baseline Karnofsky Performance Status: 90% | Participants | 4 | 0 | 4 |
| Baseline Karnofsky Performance Status: 100% | Participants | 3 | 4 | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events (TEAEs), measured over Up to 3 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the number of participants with treatment-emergent adverse events (TEAEs), with the outcome timeframe recorded as up to 3 months. The registry describes TEAEs as events reported from clinical laboratory tests, physical examinations, and vital signs, from pretreatment through 4 weeks after the last dose of study treatment. The Safety Analysis Set comprised all subjects who received at least 1 dose of study drug.
A participant count is a straightforward way to describe how many people experienced an event during the defined observation period. In an early-phase study, safety monitoring is central: the endpoint helps characterize observed adverse events while dose escalation is being considered. The count does not, by itself, describe the event types, their severity, timing, duration, or relationship to treatment. Those features require additional event-level information.
The registry also describes the objective of identifying a dose that induced a desired pyrogenic effect, defined as a body temperature of 38°C to 39.5°C. That objective is distinct from the primary TEAE count. The registry record does not report a separate primary-endpoint effect estimate or an inferential comparison. The counts of participants affected by serious and other adverse events offer safety context, but they should not be treated as a substitute for a complete account of all TEAEs.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study addresses safety and dose-finding questions in a phase 1 setting. Its design is open-label, non-randomized, and single-group, with 17 participants enrolled across two dosing cohorts. The recorded safety figures show that 1 of 13 participants in Cohort 1 and 1 of 4 participants in Cohort 2 were affected in the serious-adverse-event category. For other adverse events, the recorded figures are 13 of 13 and 4 of 4, respectively. These are descriptive counts within small cohorts, not estimates from a randomized comparison.
The difference in cohort size matters when interpreting counts: the same number of affected participants can represent different proportions in groups of different sizes. However, the registry figures do not support a causal comparison between cohorts. Cohort 1 followed an escalating-dose strategy, while Cohort 2 received a fixed dose. The groups were not randomized, and the record does not describe them as comparable at baseline. Differences could reflect factors other than dosing strategy, including participant characteristics, disease mix, or the way participants entered the cohorts; details needed to assess these possibilities are not reported in the registry record.
The serious-event terms listed in the registry include “Increased pleural effusion” at 25.0% and “Rapid disease progression” at 7.7%. These percentages are event-term entries, not a treatment-versus-control effect. The registry does not provide, alongside those entries, enough detail to establish a comparative risk, determine causality, or interpret the percentages as rates over a common follow-up period. They should be read as descriptive safety information.
The stated primary endpoint is the number of participants with TEAEs, but a separate overall count for that endpoint is not reported in the registry record. Nor is an inferential estimate, such as a confidence interval or p-value, reported. The available adverse-event counts therefore permit a limited description, not a precise estimate of the underlying event frequency. With small groups, uncertainty around any proportion would be substantial; the registry record does not report uncertainty intervals for these counts.
The study also had secondary objectives involving immune responses and tumor response. The listed outcomes indicate what the investigators intended to evaluate, but outcome titles alone do not establish what happened or how completely those outcomes were measured. The registry record does not report an inferential comparison for these objectives. The findings should consequently be interpreted as early-phase observations within this study, not as evidence from a controlled test of treatment benefit.
Overall, the posted data describe adverse-event counts in participants exposed to MBV under two dosing approaches. They do not establish that MBV caused a specific event, quantify comparative safety against another treatment, or establish tumor or immunological benefit. The open-label design, lack of a control group, small enrollment, and absence of reported inferential analyses constrain the conclusions that can be drawn.
9. Statistical Methods Explained
The registry describes a binary participant-level outcome: whether a participant was counted as having an event. For this kind of outcome, the basic descriptive result is a count of affected participants relative to the number assessed or at risk. Such counts are useful because they retain the scale of the observed data. They should be distinguished from event counts: one participant may experience more than one event, whereas a participant-level outcome counts that person according to the endpoint definition.
What does a confidence interval communicate?
In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the analysis. It is not a guarantee that the true value lies within the interval, and it does not remove limitations in the study design or data collection. For a small study, estimates of event frequency can be imprecise, even when the observed count is reported exactly. No confidence interval for the primary TEAE outcome is reported in the registry record.
Why does the study design affect the analysis?
In general, random allocation helps balance measured and unmeasured participant characteristics between treatment groups, supporting a causal comparison when the study is otherwise well conducted. This study was non-randomized and single-group, and it had no control arm. Its cohorts used distinct dosing strategies: within-subject escalation in Cohort 1 and a fixed dose in Cohort 2. Thus, cohort-level counts are descriptive. A difference between them cannot be interpreted as an unbiased estimate of the effect of one dosing strategy versus another.
Repeated dose escalation within a participant also means that exposure was not simply one fixed dose from the beginning of participation in Cohort 1. The registry description says escalation occurred for subsequent administrations in the absence of a dose-limiting toxicity, until the desired pyrogenic effect was observed. That design is relevant to interpretation because adverse events could arise at different exposure stages. The registry record does not report an analysis relating event timing or dose level to adverse events.
What can be concluded from the reported counts?
The serious and other adverse-event fields report participants at risk and participants affected for each cohort. Those figures summarize the observed participants in those categories. They do not provide a complete event-level profile, a time-to-event analysis, or a comparison adjusted for participant characteristics. The registry lists serious-event terms with percentages, but does not report enough accompanying detail to reconstruct their denominators or assess whether the terms overlap within participants. The overall primary TEAE count and an inferential estimate are not reported in the registry record.
In general, an analysis of event proportions can include an interval estimate to show sampling uncertainty. A comparison may also use a statistical test or model, but the method must match the design and estimand. Because the trial lacks a randomized comparator and the cohorts differ by dosing approach, a formal test between cohort proportions would not by itself solve confounding or establish a causal effect. The registry record does not report a statistical test or model for the safety outcomes.
How should planning calculations be viewed?
Any sample-size illustrations associated with this study are planning illustrations, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. Those assumptions describe a hypothetical planning exercise and do not match the actual study's non-randomized, single-group design. In particular, the trial did not use equal randomized allocation to two comparison arms. Such illustrations should not be read as proof that the study was adequately powered or as a retrospective measure of the chance of detecting an effect.
In general, planning calculations depend on the outcome, target effect, statistical assumptions, and intended comparison. They do not establish that a clinically meaningful effect exists. If the underlying effect estimate is uncertain, calculations based on it inherit that uncertainty. The registry record does not report a sample-size justification for the actual trial or details of how enrollment was chosen.
What analysis details remain unclear?
The registry defines the Safety Analysis Set as subjects receiving at least 1 dose of study drug. That specifies who was intended for the safety analysis, but the record does not describe how missing observations were handled, whether all participants completed follow-up, or how event attribution was determined. It also does not report interim analyses or a detailed analysis plan. These omissions limit assessment of how consistently the endpoint was applied and whether the reported summaries capture all eligible participants.
Statistical methods can describe uncertainty and support comparisons, but they cannot compensate for a design without a control group or for incomplete reporting. In this study, interpretation rests mainly on descriptive safety information and the stated study objectives. The absence of reported inferential analyses should not be mistaken for evidence that outcomes were identical, nor should descriptive counts be treated as evidence of a comparative effect.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary safety outcome and secondary outcomes concerning serum NY-ESO-1-specific immune responses and best overall tumor response. Testing or estimating multiple outcomes can raise multiplicity concerns: when many questions are examined, the chance of at least one apparently notable result can increase. In general, a prespecified hierarchy or adjustment can help address that issue, but the registry record does not report a multiplicity strategy, a detailed statistical analysis plan, or inferential analyses for the listed outcomes.
Missing-data handling is also not reported in the registry record. The Safety Analysis Set is defined as subjects who received at least 1 dose of study drug, but that definition alone does not explain whether every participant had complete safety follow-up, how incomplete assessments were handled, or whether participants were excluded from particular outcomes. The record does not report the amount or pattern of missing outcome data.
The safety population is specified, but analysis populations for the immune-response and tumor-response outcomes are not described in detail in the registry record. It is therefore not possible to determine whether those outcomes used the same participants, how evaluability was defined, or how incomplete assessments affected the summaries. These reporting gaps limit reproducibility and make it difficult to judge whether all intended outcome information contributed to the results.
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 |
|---|---|---|---|
| Cohort 1 | 1 | 13 | 7.7% |
| Cohort 2 | 1 | 4 | 25.0% |
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 |
|---|---|
| Cohort 1 | 13 of 13 |
| Cohort 2 | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1 | Cohort 2 |
|---|---|---|---|
| Rapid disease progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 13 | 0 of 4 |
| Increased pleural effusion | Respiratory, thoracic and mediastinal disorders | 0 of 13 | 1 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 | Cohort 2 |
|---|---|---|---|
| Pain at injection site | General disorders | 4 of 13 | 2 of 4 |
| CRP elevation | Investigations | 3 of 13 | 2 of 4 |
| Edema | General disorders | 4 of 13 | 0 of 4 |
| Weakness | General disorders | 2 of 13 | 2 of 4 |
| Chills | General disorders | 1 of 13 | 2 of 4 |
| Fever | General disorders | 2 of 13 | 1 of 4 |
| Hypertension | Vascular disorders | 2 of 13 | 1 of 4 |
| Hypotension | Vascular disorders | 3 of 13 | 0 of 4 |
| Nausea | Gastrointestinal disorders | 2 of 13 | 1 of 4 |
| Tachycardia | Cardiac disorders | 2 of 13 | 1 of 4 |
Serious events with the highest arm-level rate: increased pleural effusion (25.0%), rapid disease progression (7.7%).
The serious-adverse-event figures are participant counts within the two cohorts: 1 of 13 in Cohort 1 and 1 of 4 in Cohort 2. The registry also reports other adverse events for 13 of 13 participants in Cohort 1 and 4 of 4 in Cohort 2. These categories are descriptive and should not be added together: the record does not say whether the same participants appear in both categories, and a participant can experience more than one event.
The listed serious-event terms are “Increased pleural effusion” at 25.0% and “Rapid disease progression” at 7.7%. These entries should be read as reported term-specific percentages, not as comparative treatment effects. The registry record does not provide enough detail to establish their denominators, overlap, timing, or relationship to study treatment. In particular, an adverse event recorded during a study is not, by that fact alone, established as caused by the intervention.
The cohorts were small, non-randomized, and exposed under different dosing approaches. Their counts are not a controlled comparison of safety. The registry does not report uncertainty intervals for these figures, so they should not be read as precise estimates of event frequency in a broader population.
12. What the Result Does, and Does Not, Mean
The study provides descriptive safety information for 17 participants enrolled in a phase 1 investigation of MBV. It records serious-event counts of 1 of 13 in Cohort 1 and 1 of 4 in Cohort 2, along with other-adverse-event counts of 13 of 13 and 4 of 4, respectively. It also lists two serious-event terms with percentages. These observations characterize what was recorded in the study; they do not establish how often similar events would occur in a broader population.
The results do not establish a comparative safety effect because there was no randomized control group. The two cohorts were not like-for-like treatment arms: one used dose escalation within participants and the other used a fixed dose. The results also do not show that any reported event was caused by MBV. Assessing causality requires more than knowing that an event occurred during a study; the registry record does not report the information needed for a causal determination.
The study's stated objectives included identifying a dose that induced the desired pyrogenic effect and evaluating immune response and tumor response. The primary endpoint was the participant count with TEAEs, but a separate overall TEAE result is not reported in the registry record. The registry lists the secondary outcomes, but their titles do not establish the observed immune or tumor results. No inferential comparison for those outcomes is reported.
Accordingly, the findings are best understood as early-phase observations from a small, open-label, non-randomized study. They do not establish treatment benefit, demonstrate equivalence between the cohorts, or support a general conclusion about safety across the listed tumor types. The lack of reported uncertainty estimates also means that the precision of the event-frequency estimates cannot be assessed from the registry record.
13. Why This Trial Matters Statistically
This study illustrates the distinct role of early-phase research: describing safety and exploring dose administration before questions of comparative effect can be addressed. Its protocol used two different dosing strategies, including within-subject escalation in one cohort and a fixed dose in another. That makes it especially important to distinguish a descriptive cohort summary from a controlled estimate of a dosing effect.
It also demonstrates why denominator context matters for event counts. The serious-event count is 1 participant in each cohort, but the cohort sizes differ. Presenting the count alongside the number at risk prevents the reader from treating equal counts as equivalent evidence about risk. At the same time, small groups and the absence of reported uncertainty intervals limit how precisely those counts can characterize event frequency.
Another statistical lesson is that endpoint titles, objectives, and results answer different questions. The registry states that immune response and tumor response were secondary objectives, but the outcome titles alone do not establish what was observed. Similarly, a safety endpoint defined as participants with TEAEs does not capture every detail needed to assess event severity, timing, or causal relationship.
Finally, planning calculations must be distinguished from the design actually used. A planning illustration based on two equally allocated arms is not the same as the study's non-randomized, single-group design. Recognizing that distinction prevents a hypothetical sample-size exercise from being mistaken for evidence of adequate power or for an analysis of the observed cohorts. Clear reporting of analysis plans, missing data, and uncertainty would further support interpretation.
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 design limitation is the absence of a randomized control group. The study was open-label, non-randomized, and single-group, so its adverse-event observations cannot be compared with an untreated or alternative-treatment group in a way that isolates the effect of MBV. The two cohorts were not like-for-like controls: Cohort 1 used dose escalation within each subject, while Cohort 2 received a fixed dose determined from Cohort 1.
Enrollment was 17, with 13 participants at risk in Cohort 1 and 4 in Cohort 2 for the reported adverse-event categories. These small cohorts limit the precision and generalizability of descriptive counts. The registry record does not report confidence intervals for the event summaries, participant characteristics by cohort, or the criteria used to place participants into each cohort. It is therefore difficult to assess how comparable the cohorts were or how representative they were of the listed tumor populations.
The primary endpoint is described, but a separate overall count of participants with TEAEs is not reported in the registry record. The posted safety information does not provide a complete event-level account or enough detail to assess timing, severity, duration, attribution, and overlap for all events. The registry record also does not report how missing observations were handled or whether follow-up was complete for each participant.
Although immune response and tumor response were listed as secondary objectives, the registry record does not provide inferential analyses for those outcomes. It does not report a detailed statistical analysis plan, a multiplicity approach, interim analyses, or a sample-size justification for the actual design. These reporting gaps restrict assessment of the precision, completeness, and reproducibility of the reported findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase 1 Study of Mixed Bacteria Vaccine (MBV) in Patients With Tumors Expressing NY-ESO-1 Antigen — NCT00623831.
- Registry record last updated 2022-10-25; status last verified 2022-10.
- Results first posted 2017-01-09.
- 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.
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18. Record Summary
The registry record describes a completed phase 1, open-label, non-randomized, single-group study of mixed bacterial vaccine in participants with tumors expressing NY-ESO-1. Enrollment was 17. Cohort 1 received twice-weekly MBV starting at 250 EU, with within-subject escalation in the absence of dose-limiting toxicity; Cohort 2 received twice-weekly MBV at a fixed dose of 60,800 EU.
The primary objective was safety characterization and identification of a dose inducing the specified pyrogenic effect. The primary outcome was the number of participants with treatment-emergent adverse events, with a timeframe up to 3 months. The registry reports serious and other adverse-event counts by cohort, but does not report a separate overall TEAE count or inferential estimate. Secondary objectives concerned immune response and tumor response. The absence of a randomized comparator, the small cohorts, and unreported analysis details limit interpretation to descriptive observations.