BLP25 Liposome Vaccine and Bevacizumab After Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BLP25 Liposome Vaccine and Bevacizumab After Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery (NCT00828009), a na phase 2 study. The primary outcome is Proportion of Patients With Target Adverse Events for the Step 2 Treatment.

2. Clinical Question

The study addresses safety in a treatment sequence for patients whose cancer could not be removed by surgery. The primary endpoint concerns a defined set of adverse events: grade 4-5 hemorrhage, esophagitis, fistula, platelet count decrease (thrombocytopenia), encephalitis infection, or hepatic failure episodes. Assessment was scheduled every 3 weeks while on treatment and up to 5 years.

This is not a randomized comparison of maintenance treatment against another treatment or observation. It therefore does not directly estimate a between-group difference in safety or establish how the observed events compare with what would have occurred under another approach. The registry lists overall survival and progression-free survival as secondary outcomes, but their results are not reported in the registry record. The stated primary question is about the frequency of specified safety events, not whether treatment improves survival or controls cancer.

3. Trial Design

This was a phase II, single-group study sponsored by ECOG-ACRIN Cancer Research Group. The registry reports enrollment of 70 and a completed status. The recorded start date is 2011-01-17, and primary completion is dated 2018-08-20. Allocation is listed as NA and masking as none. These design features mean the record does not describe randomized assignment or a masked comparison.

The treatment sequence began with chemoradiation. The arm description states that patients received weekly paclitaxel and carboplatin alongside radiotherapy given 5 days a week for 6½ weeks. Patients with CR, PR, or SD proceeded to consolidation chemotherapy. The registry lists bevacizumab, tecemotide, carboplatin, cyclophosphamide, paclitaxel, and radiotherapy among the interventions. The arm description in the registry record is incomplete, so further regimen details are not reported in the registry record.

The primary endpoint population is all patients who received step 2 treatment, identified as maintenance therapy. The registry describes the primary outcome as the proportion with target adverse events and gives a follow-up period extending from assessments during treatment to up to 5 years. The safety record separately lists step 1 and step 2 groups, including participants at risk and counts with serious adverse events, other adverse events, and deaths.

A statistical analysis plan, details of any interim analyses, and a sample-size justification are not reported in the registry record. The record does not describe a randomized control arm. Consequently, the study design supports description of outcomes in the treated groups but does not, by itself, provide a randomized estimate of treatment differences.

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.

Step 1 - Chemo RT/Consolidation Chemo

Reasons for not completing this period:

Step 2 - Maintenance Therapy

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All patients who received step 2 treatment

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: The primary objective was to determine the safety of combination therapy with chemoradiation, followed by consolidation, finally followed by tecemotide and bevacizumab for this patient population. Only patients who started step 2 protocol therapy were included in this analysis.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Patients With Target Adverse Events for the Step 2 Treatment, measured over Assessed every 3 weeks while on treatment and up to 5 years.

The primary endpoint is the proportion of patients with specified target adverse events for step 2 treatment. It focuses on safety of tecemotide immunotherapy combined with bevacizumab. The target events are grade 4-5 hemorrhage, esophagitis, fistula, platelet count decrease (thrombocytopenia), encephalitis infection, or hepatic failure episodes. The endpoint population is all patients who received step 2 treatment.

The registry specifies assessment every 3 weeks while on treatment and up to 5 years. A proportion is a way to describe how often an event or defined event category occurs among people in a stated population. It can make a safety outcome interpretable in relation to the group being monitored. However, the registry record does not report the primary endpoint estimate, its numerator or denominator, or a confidence interval. The listed safety counts for serious adverse events are not identified as the primary endpoint result and should not be substituted for it.

In general, a confidence interval communicates statistical uncertainty around an estimate; a wider interval indicates less precision than a narrower one. The registry specifies an 80% confidence interval as the endpoint’s dispersion measure, but no interval estimate is reported in the registry record. The endpoint’s timing and event definition are stated, while the detailed rules for counting events or handling repeated events are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a proportion, a summary used for binary outcomes: each person’s status is classified according to whether the defined outcome occurred under the study’s counting rules. The resulting proportion describes the observed frequency in the stated population. For this study, the registry identifies the population as all patients who received step 2 treatment and names the target adverse events. It does not report the outcome count, the corresponding denominator used in the endpoint analysis, or the event-counting rules in enough detail to reproduce an estimate.

What does a confidence interval add?

In general, a confidence interval gives a range of values compatible with the observed data under a statistical model. It conveys uncertainty about the estimated population value rather than certainty about an individual patient’s outcome. A narrower interval usually indicates greater precision, while a wider interval indicates more uncertainty. The registry specifies an 80% confidence interval for the primary endpoint, but it does not report the interval itself or the method used to calculate it. Without those results, the stated confidence level alone does not establish how precise the endpoint estimate was.

Why does the study design matter?

The study is recorded as single group, with allocation listed as NA and masking listed as none. In general, a single-group study can describe outcomes observed during treatment, but it lacks a randomized concurrent group for estimating a treatment contrast. Differences between treatment steps would not constitute a randomized comparison: patients enter step 2 after earlier treatment, and the registry does not describe assignment to the steps as random. A comparison of the step-specific safety counts therefore should not be interpreted as a causal estimate of the effect of maintenance therapy.

The registry lists enrollment of 70, but the primary endpoint applies to patients who received step 2 treatment. Enrollment and the endpoint analysis population are not interchangeable. The registry reports 33 at risk in the step 2 safety entry, but it does not report whether this is the denominator used for the primary endpoint estimate, which is not reported in the registry record. A denominator should not be inferred from another safety summary unless the record explicitly links them.

What can the adverse-event listings tell readers?

Counts of participants affected provide a descriptive account for the named group and category. The serious adverse event and other adverse event fields are separate summaries. The listed serious terms and percentages add detail about the types of events recorded, but the registry does not explain the percentage denominator or whether participants could appear under multiple terms. These listings do not establish that every listed term is part of the primary endpoint’s defined target-event set.

In general, over-dispersion matters when data vary more than a statistical model expects. For example, treating clustered or highly variable counts as if they followed a simpler model can make uncertainty appear too small. That issue may be relevant to some count-based analyses, but the registry does not report a count model or a method for accounting for over-dispersion in this study. No claim can be made that such a method was used.

How should planning calculations be read?

A planning illustration based on an observed effect is not an observed trial outcome and is not observed power. The stated illustration assumptions are two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The record explicitly says that these are planning assumptions rather than the trial’s own design. They do not turn this single-group study into a randomized two-arm study, and they cannot supply the missing primary endpoint result. The registry does not report the trial’s sample-size justification.

In general, a statistical analysis plan would specify the estimand, analysis population, outcome definition, estimation method, and treatment of uncertainty. For this study, the registry reports the primary outcome’s broad definition, population, assessment schedule, and confidence level. The analysis method, interim analyses, missing-data procedures, and multiplicity strategy are not reported in the registry record. The registry lists no analysis records. Thus, readers can identify the intended safety question and some descriptive safety entries, but cannot reproduce the primary analysis or assess its precision from the reported information.

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("Step 2 - Maintenance Therapy")
n      <- c(33)
events <- c(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  Step 2 - Maintenance Therapy  33  0  0.0  0.0  10.6  0.0  10.4  0.1  10.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists overall survival and progression-free survival as secondary outcomes alongside the primary safety endpoint. It does not report results for those outcomes or describe a plan for controlling multiplicity across outcomes. A multiplicity approach matters when several outcomes or analyses are evaluated, because interpreting each result independently can increase the chance of at least one apparently notable finding. Whether the study used an adjustment, a hierarchy, or another strategy is not reported in the registry record.

Missing-data methods are also not reported in the registry record. The record does not state how participants with incomplete follow-up, unavailable assessments, or treatment discontinuation were handled in the primary endpoint analysis. It does not provide a missingness summary for that endpoint. Consequently, the impact of missing outcome information on the intended proportion cannot be assessed.

The primary population is described as all patients who received step 2 treatment. That definition is distinct from the enrollment figure and from the step-specific safety summaries. The registry does not describe additional analysis populations or explain how population membership was determined for each outcome. The record lists no analysis records, so it does not supply an analysis-level account of endpoint denominators, exclusions, or model specifications.

In general, multiplicity and missing-data decisions affect how results should be interpreted, but no particular method should be assumed when it is not documented. The registry record does not report an interim-analysis plan, a statistical analysis plan, or sensitivity analyses addressing these issues.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: white blood cell decreased (20.6%), hypertension (18.2%), neutrophil count decreased (16.2%), lymphocyte count decreased (10.3%), fatigue (8.8%).

The registry reports serious adverse event summaries by treatment step. In step 1, 39 of 68 participants at risk were listed as affected; in step 2, 11 of 33 were listed as affected. The corresponding entries for other adverse events are 65 of 68 in step 1 and 32 of 33 in step 2. Death counts are listed as 48 for step 1 and 21 for step 2. These are registry summaries, not estimates of treatment-attributable risk.

The record does not give the timing, causes, or attribution of the deaths. It also does not clarify whether participants could be counted in more than one adverse-event term or how the listed percentages were calculated. The top serious adverse event terms and recorded percentages are White blood cell decreased, 20.6%; Hypertension, 18.2%; Neutrophil count decreased, 16.2%; Lymphocyte count decreased, 10.3%; Fatigue, 8.8%; and Dehydration, 7.4%.

These summaries should not be mistaken for the primary endpoint result. That endpoint concerns a specified set of target adverse events among step 2 recipients, and its estimate is not reported in the registry record. In general, adverse-event counts describe what was recorded; interpretation of comparative risk requires comparable groups and clear definitions, timing, and denominators.

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

The record establishes the study’s intended safety question and its treatment context: tecemotide with bevacizumab as maintenance after chemoradiation and consolidation chemotherapy for unresectable stage IIIA or stage IIIB non-squamous non-small cell lung cancer. It also reports group-level safety counts and selected serious adverse event terms. Those entries can be read as descriptive information about events recorded during the study.

The primary endpoint result is not reported in the registry record. There is no posted proportion for the target adverse events, no confidence interval estimate, and no endpoint analysis details that would allow the primary safety question to be answered quantitatively. The listed serious adverse event counts do not substitute for that outcome because the record does not establish that they use the primary endpoint’s target-event definition or analysis population.

The study is single group and has no randomized comparator. It therefore does not estimate the difference in safety or survival between maintenance treatment and an alternative. The listed deaths cannot be attributed to treatment from these data, and the secondary outcomes of overall survival and progression-free survival have no reported results in the record. No conclusion about treatment benefit or lack of benefit follows from the information reported.

In general, a registry entry is useful for understanding a study’s stated aims, design, populations, and selected outcome reporting. A complete interpretation of an endpoint also requires its observed estimate, uncertainty, analysis population, and relevant methods. Those details are absent for the primary endpoint in this record, so its magnitude and precision cannot be assessed.

14. Why This Trial Matters Statistically

This study raises a focused statistical question: how often a defined set of serious target adverse events occurred among patients receiving tecemotide and bevacizumab after prior chemoradiation. Stating the target events, population, and assessment period helps distinguish the intended endpoint from broad adverse-event reporting. The distinction matters because general safety summaries and a prespecified endpoint need not include the same events or use the same analysis population.

The record also illustrates why study design determines what conclusions are available. A single-group study can document observed outcomes, while a randomized comparator would be needed to estimate a controlled between-group difference. Since allocation is listed as NA and no comparator group is described, the safety entries should be treated as descriptive rather than as evidence of a causal treatment effect.

Precision is another central issue. The registry specifies an 80% confidence interval for the primary endpoint, but does not report the estimate or interval. Without them, readers cannot judge the uncertainty around the intended safety measure. Similarly, the listed step-specific event counts are not enough to reconstruct the endpoint or its uncertainty when the relationship between those summaries and the primary endpoint is not stated.

The record’s secondary outcome names, safety summaries, and treatment sequence provide useful context, but they do not replace a reported endpoint analysis. Statistically, the key lesson is to keep the endpoint definition, analysis population, study design, and available results aligned when interpreting a clinical trial.

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 main limitation for statistical interpretation is that the registry record does not report the primary endpoint estimate or its confidence interval. Although it specifies the target events, assessment schedule, and endpoint population, it does not provide the endpoint count, denominator, or analysis method. The primary safety question therefore cannot be quantified from the record.

The design is single group, with allocation recorded as NA and masking as none. No randomized comparator is described. As a result, the reported safety summaries do not support a controlled estimate of treatment differences. The registry does not report results for the listed secondary outcomes of overall survival and progression-free survival, so those outcomes cannot be interpreted from this record either.

Additional details needed to evaluate the summaries are not reported in the registry record: the handling of missing assessments, multiplicity methods, interim analyses, analysis populations beyond the stated primary population, and the statistical analysis plan. The relationship between the adverse-event summaries and the primary endpoint is also not specified. The denominators and reporting basis for the listed serious adverse event percentages are not explained.

The arm description is incomplete in the registry record, limiting the treatment details that can be recovered from it. Enrollment, step-specific safety counts, and deaths are reported, but these should not be combined or treated as a substitute for an endpoint analysis. In general, incomplete outcome and methods reporting limits reproducibility and the precision of conclusions that can be drawn from registry summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: BLP25 Liposome Vaccine and Bevacizumab After Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery — NCT00828009.
• Registry record last updated 2023-07-07; status last verified 2023-06.
• Results first posted 2019-03-26.
• 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

NCT00828009 is a completed phase II, single-group study sponsored by ECOG-ACRIN Cancer Research Group. It enrolled 70 and studied tecemotide with bevacizumab after chemoradiation for unresectable stage IIIA or stage IIIB non-squamous non-small cell lung cancer. Allocation is listed as NA and masking as none. The recorded start date is 2011-01-17, and primary completion is dated 2018-08-20.

The primary outcome is the proportion of step 2 recipients with specified target adverse events, assessed every 3 weeks while on treatment and up to 5 years. The registry lists overall survival and progression-free survival as secondary outcomes. It reports selected adverse-event counts and terms, but the primary endpoint result and secondary outcome results are not reported in the registry record. A statistical analysis plan, missing-data methods, and multiplicity methods are also not reported.