Vaccine Therapy, Tretinoin, and Cyclophosphamide in Treating Patients With Metastatic Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vaccine Therapy, Tretinoin, and Cyclophosphamide in Treating Patients With Metastatic Lung Cancer (NCT00601796), a na phase 2 study. The primary outcome is Number of Evaluable Participants With Tumor Response.

2. Clinical Question

This is principally an immune-response question rather than a direct comparison of treatment strategies. The record describes PBMC collection at baseline and after each vaccination, with T-cell activation profiles assessed by ELISpot assay. It also lists median time to progression, median overall survival, and serious adverse events among the secondary outcomes. However, the registry record does not report numerical results for the primary endpoint or those secondary outcomes. The endpoint title refers to tumor response, while its description defines the measured response as sustained peptide-specific T-cell activation; these terms should be read in light of that operational definition.

3. Trial Design

The registry record describes a phase 2, completed, single-group study of combination immunotherapy for lung cancer. Its listed enrollment is 24. The intervention group is described as receiving vaccine treatment, cyclophosphamide, and ATRA. Allocation is recorded as not applicable, and masking is recorded as none. There is no randomized control group or like-for-like comparison arm in the design information.

The study started in 2006-10 and had a primary completion date of 2012-06. The primary outcome timeframe is 3 years. The registry describes the primary measure as the number of evaluable participants with tumor response, operationally defined as sustained tumor peptide-specific T-cell activation after vaccination among participants with evaluable PBMCs. The endpoint population is stated as 14 participants with evaluable PBMCs.

The registry lists median time to progression, median overall survival, and the number of participants with serious adverse events as secondary outcomes. It also lists four outcome measures, but the record does not provide numerical results for the primary outcome or the secondary outcomes described. No analysis results are listed. Details such as the rationale for the enrollment target, a full statistical analysis plan, and whether any interim analyses were planned are not reported in the registry record.

Because this is a single-group study, observations can describe outcomes among participants receiving the combination, but they cannot by themselves establish how those outcomes compare with outcomes under another treatment or no treatment. The record’s lack of a comparator is central to interpreting both efficacy-related and safety information.

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

Analysis population for the primary outcome, as defined in the registry: 14 participants with evaluable PBMCs

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: 24 participants were accrued at a single center from 10/2006 to 6/2008. There were 14 participants with evaluable peripheral blood mononuclear cells (PBMCs).

6. Primary Endpoint

The registry lists the primary outcome as Number of Evaluable Participants With Tumor Response, measured over 3 years.

The primary endpoint is titled “Number of Evaluable Participants With Tumor Response.” Its description specifies that the response of interest is sustained tumor peptide-specific T-cell activation after vaccination, assessed in participants with evaluable PBMCs. PBMC samples were collected at baseline and after each vaccination, and activation profiles were analyzed using an ELISpot assay. The endpoint population is stated as 14 participants with evaluable PBMCs, and the timeframe is 3 years.

This type of endpoint can characterize whether an immune response is observed during treatment. As a general statistical point, a count endpoint communicates how many people meet a defined criterion, while the criterion itself determines what the count means. Here, the description focuses on an immune assay response, not a direct measure of tumor shrinkage or survival. Although the title uses the phrase “tumor response,” the operational definition in the record is sustained T-cell activation.

The registry also says activation profiles were tested by generalized Wilcoxon for correlation with survival. That describes an analysis approach, not a reported finding. The registry record does not report the number meeting the primary endpoint, an estimate of the association with survival, or uncertainty around either quantity. The endpoint’s clinical interpretation is therefore limited by the absence of posted numerical results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design allow?

The study is listed as single-group, with allocation not applicable and no masking. That means the record describes outcomes among participants receiving the combination, rather than a randomized contrast between treatments. As a general statistical point, a comparator helps distinguish outcomes associated with an intervention from outcomes that might also occur because of the underlying disease, other care, or chance. Without such a group, observed changes or events cannot be attributed to the combination by comparison with an alternative within this trial.

What does the primary endpoint count?

The primary measure is a count of participants meeting a specified immune-response criterion. The description defines that criterion as sustained tumor peptide-specific T-cell activation after vaccination among participants with evaluable PBMCs. The record states that samples were collected at baseline and after each vaccination and that an ELISpot assay was used. The endpoint title’s wording about tumor response should not obscure the more specific assay-based definition in the description.

For a count endpoint, interpretation depends on the population assessed, the rule for classifying a response, and the number who meet that rule. The registry identifies 14 participants with evaluable PBMCs but does not report the count meeting the response criterion. It also does not report an interval estimate. As a general statistical concept, a confidence interval expresses uncertainty around an estimate; without a posted estimate and interval, the precision of the primary result cannot be evaluated.

What is the role of the generalized Wilcoxon test?

The endpoint description says that T-cell activation profiles were tested by generalized Wilcoxon for correlation with survival. In general, a test of association evaluates whether observed patterns in one measure are related to another under specified assumptions. The name of a test does not reveal the estimated association, its uncertainty, or whether the finding met a chosen decision threshold. The registry record does not report those results, nor does it provide further details of the implementation or assumptions.

How should the secondary outcomes be understood?

The listed secondary outcomes are median time to progression, median overall survival, and the number of participants with serious adverse events. These are different kinds of outcomes: time-to-event measures describe the timing of an event, while an adverse-event count describes how many participants were affected. As a general statistical point, time-to-event analyses can account for differing follow-up and censoring, but their interpretation depends on definitions, follow-up, and analysis details. Those details and numerical results are not reported in the registry record in the registry record.

The record lists four outcome measures, but no analysis results. It is not possible to infer from the outcome list whether every measure was analyzed as planned, how missing observations were handled, or whether results were selected for reporting. Those details are not reported in the registry record.

Why does over-dispersion matter?

As a general statistical concept, over-dispersion occurs when observed variability is greater than a statistical model expects. It can make standard errors too small if the model assumes less variability than the data contain. This consideration is relevant to some count-data analyses, but the record information does not identify an over-dispersion model or provide a fitted count analysis. It would be inappropriate to attribute a particular method to this trial.

What do planning illustrations represent?

Planning illustrations are not trial outcomes. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The trial itself is single-group, so those hypothetical two-arm assumptions do not describe its design. The stated method also distinguishes event totals for time-to-event illustrations from participants per arm for other illustrations. Such calculations are planning aids, not observed power or evidence of an effect in this study. The registry record does not report the numerical observed effect used for the illustration in the registry record, so no planning result can be interpreted from them.

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("Combination Immunotherapy")
n      <- c(14)
events <- c(5)
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  Combination Immunotherapy  14  5  35.7  12.8  64.9  16.3  61.2  16.3  61.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcomes, and states that there are four outcome measures. It does not report a multiplicity adjustment or a hierarchy for testing the outcomes. When several hypotheses are tested, the chance of at least one false-positive finding can increase; as a general statistical matter, a prespecified testing strategy can help explain how multiple results should be interpreted. The registry record does not report such a strategy, so it is not possible to determine how multiplicity was addressed.

The primary endpoint description identifies 14 participants with evaluable PBMCs, while listed enrollment is 24. The record does not explain the evaluability criteria, reasons for unavailable PBMC measurements, or how missing endpoint data were handled. Missingness can affect interpretation if participants without measurements differ systematically from those with measurements; this is a general concern, not a finding about this trial.

The registry record does not report a complete analysis-population definition, a participant flow for the primary endpoint, or whether the analysis included all enrolled participants, only participants who received treatment, or another defined group. The stated evaluable-PBMC population is the only specific primary-endpoint population description in the registry record. The record also does not provide details of imputation, sensitivity analyses, or missing-data assumptions. These omissions limit assessment of how robust the endpoint result would be to incomplete observations; no result is reported to assess in the first place.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnea (shortness of breath) (12.5%), pain - tumor pain (8.3%), hypoxia (8.3%), hemoglobin (4.2%), supraventricular and nodal arrhythmia - nos (4.2%).

For the combination immunotherapy group, the registry lists 24 participants at risk for serious adverse events and 11 affected. For other adverse events, it lists 24 at risk and 24 affected. These are participant counts, not counts of individual event episodes. The record does not report deaths in the provided safety information.

The listed serious adverse event terms include dyspnea (shortness of breath) at 12.5%, tumor pain at 8.3%, hypoxia at 8.3%, hemoglobin at 4.2%, supraventricular and nodal arrhythmia - NOS at 4.2%, and hypotension at 4.2%. These are registry-listed terms and percentages; the information does not establish that each term represents a separate participant, nor does it give an event-level accounting in the registry record. The percentages should not be combined or treated as mutually exclusive categories.

As a general statistical point, an adverse event occurring during a study is not automatically caused by the intervention. A single-group safety record cannot provide a comparative estimate of whether events were more or less common under another treatment. The counts describe what was recorded for this group, not a causal effect or a comparison with an untreated population.

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

The record establishes that a completed phase 2 study evaluated a vaccine, cyclophosphamide, and ATRA together in a single group of patients with lung cancer. Its primary endpoint focused on sustained tumor peptide-specific T-cell activation among participants with evaluable PBMCs. The safety record also reports participant counts for serious and other adverse events, and lists selected serious-event terms with percentages.

These registry entries do not establish the size or precision of the primary immune-response result because its numerical count and uncertainty are not reported in the registry record. The record also does not report numerical results for time to progression, overall survival, or the stated association between T-cell activation and survival. A stated endpoint or analysis method is not itself a finding.

The immune assay endpoint should not be read as a direct demonstration of tumor shrinkage or a survival benefit. The endpoint description defines the measured response as T-cell activation, even though the endpoint title uses the phrase “tumor response.” The registry information does not provide a treatment comparison, so it cannot show how the observed outcomes differ from outcomes under another approach.

The safety counts are descriptive. Without a comparator and further detail, they do not determine whether an event was caused by treatment or how safety would compare with another group. Nor does completion status supply missing outcome results. The appropriate statistical reading is therefore bounded: the record describes the study design and selected safety information, but the key numerical efficacy findings and their precision are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between an immune-response endpoint and a clinical outcome. The primary endpoint is based on sustained T-cell activation measured from PBMCs, while the secondary outcomes include time to progression and overall survival. These endpoints address different questions and should not be treated as interchangeable. A laboratory response can be scientifically relevant without directly quantifying a clinical outcome.

The record also illustrates why population definitions matter. The overall enrollment is 24, while the primary endpoint description identifies 14 participants with evaluable PBMCs. Without details about eligibility for the endpoint, missing samples, and analysis populations, readers cannot determine why those populations differ or how that difference affects interpretation.

Design is equally important. A single-group study can describe experience under a combination regimen, but it does not provide a randomized comparison. As a general statistical principle, a control group is needed to estimate a comparative treatment effect while accounting for differences that may arise from factors other than treatment. The registry’s safety counts therefore remain descriptive rather than comparative.

Finally, the record states an analysis approach for relating immune profiles to survival, yet reports no numerical result for that analysis. This highlights the difference between naming a method and presenting an estimate with its uncertainty. Transparent reporting of endpoint counts, analysis populations, uncertainty, missing-data handling, and secondary outcomes is necessary for readers to judge the evidence. Those details are not reported in the registry record in the registry record.

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 principal limitation for interpretation is that the registry information does not include numerical results for the primary endpoint, the survival outcomes, or the described association between immune activation and survival. Without estimates and measures of uncertainty, the magnitude and precision of any findings cannot be assessed.

The single-group design provides no randomized comparator. It therefore cannot support a like-for-like estimate of how outcomes differ under another treatment. Masking is recorded as none, and the record does not describe additional measures to reduce assessment or reporting bias.

The primary endpoint’s stated population is 14 participants with evaluable PBMCs, compared with listed enrollment of 24. Reasons for this endpoint population, the response-classification criteria in greater detail, and methods for handling missing data are not reported in the registry record. These gaps limit evaluation of selection and measurement concerns.

The registry lists safety counts and selected serious adverse event terms, but the registry entries do not provide event-level detail, attribution, or comparative data. The listed percentages should not be treated as comparative risks. Further limitations—including the rationale for enrollment, any interim analyses, and a complete statistical analysis plan—are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Vaccine Therapy, Tretinoin, and Cyclophosphamide in Treating Patients With Metastatic Lung Cancer — NCT00601796.
• Registry record last updated 2013-05-24; status last verified 2013-02.
• Results first posted 2013-05-15.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This completed phase 2 study evaluated vaccine treatment with cyclophosphamide and ATRA in a single group of patients with lung cancer. Listed enrollment was 24; the primary endpoint description identifies 14 participants with evaluable PBMCs. The primary measure concerned sustained tumor peptide-specific T-cell activation after vaccination, with a timeframe of 3 years.

The registry lists time to progression, overall survival, and serious adverse events as secondary outcomes. It records 11 participants affected by serious adverse events among 24 at risk, and 24 affected by other adverse events among 24 at risk. Numerical results for the primary endpoint and the listed survival outcomes are not reported in the registry record. The design has no randomized comparator, so the posted safety counts are descriptive rather than comparative.