Phase II Study of Metastatic Cancer That Overexpresses P53 Using Lymphodepleting Conditioning Followed by Infusion of Anti-P53 TCR-Gene Engineered Lymphocytes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study of Metastatic Cancer That Overexpresses P53 Using Lymphodepleting Conditioning Followed by Infusion of Anti-P53 TCR-Gene Engineered Lymphocytes (NCT00393029), a non-randomized phase 2 study. The primary outcome is The Number of Participants With Adverse Events.

2. Clinical Question

3. Trial Design

This was a phase 2, non-randomized, unmasked study with a parallel model. The registry lists an enrollment of 12 and a completed status. The study began in 2006-10, with primary completion in 2008-11. Its stated focus was metastatic cancer overexpressing p53 and treatment with lymphocytes engineered to contain an anti-p53 protein.

Eligibility described in the registry included age 18 years and older, metastatic cancer, p53 overexpression in the tumor, and HLA-A 0201. The record divides participants into a metastatic melanoma group and a group with other metastatic cancers. These groups are not randomized treatment arms and should not be interpreted as an intervention-versus-control comparison. Their different underlying cancer types also mean that differences between their event counts would not isolate a treatment effect.

The treatment description includes two leukapheresis procedures. Cells collected during the first were grown in the laboratory and transduced with the anti-p53 protein; cells from the second were used to evaluate treatment effectiveness. Chemotherapy was given intravenously for one week to suppress immune activity before the engineered-cell infusion. The brief description also reports IL-2 infusions following the cell infusion. Listed interventions include aldesleukin, filgrastim, cyclophosphamide, and fludarabine phosphate, as well as the engineered lymphocytes.

The registry does not report a separate control group, randomization procedure, masking, or a detailed statistical analysis plan. Further protocol details, including the complete treatment schedule and the rationale for the enrollment target, are not reported in the registry record.

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

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as The Number of Participants With Adverse Events, measured over events related to all components of the treatment regimen were reported from the start of the non-myeloablative conditioning regiment through 30 days following treatment or resolution..

The primary endpoint is the number of participants with adverse events. It counts participants who experienced an event rather than measuring event severity as a continuous quantity or estimating the time until an event. The registry says adverse events were described using Common Terminology Criteria for Adverse Events, version 3. It defines the reporting period as starting with non-myeloablative conditioning and continuing through 30 days following treatment or resolution. Events related to all components of the regimen were included.

Safety outcomes are useful in early-phase clinical research because they describe the adverse events observed during and after an intervention and can help characterize the treatment regimen's tolerability in the studied participants. A participant count is straightforward to interpret as a count, but by itself it does not show the timing, duration, severity distribution, or clinical course of each event. The registry points readers to the adverse event module for detailed event listings; detailed terms are not included in the posted results.

The posted primary outcome does not establish treatment effectiveness. Although a secondary outcome concerns in vivo survival of T-cell receptor gene-engineered cells, the registry record does not report an efficacy comparison or a numerical result for that outcome in the registry record for this analysis. The adverse-event endpoint therefore supports a description of reported safety counts, not a conclusion about clinical benefit.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how observations are summarized and how much uncertainty is attached to a result. For a safety endpoint expressed as the number of participants with an event, the direct descriptive summary is a count within the relevant group. Such a count answers how many participants in the recorded at-risk group were reported to have an event. It is not, by itself, a comparison of treatments or a complete account of the number and course of events.

What does a participant count represent?

A participant-based count classifies each participant according to whether an event was recorded during the defined reporting period. This differs from counting every episode: one participant can have more than one event, while the participant remains one person in the participant count. The primary outcome is described as the number of participants with adverse events, and the record gives serious and other adverse-event counts by cancer group. The record does not provide individual-level data or detailed event listings in the registry record for this analysis, so event frequency per participant and event timing cannot be reconstructed.

The reporting window matters because an event outside that window may not be represented in the endpoint. In this study, the registry describes reporting from the start of the non-myeloablative conditioning regimen through 30 days following treatment or resolution. The record does not explain how events after that period were collected or whether later follow-up was used for other outcomes. Interpretation should therefore remain tied to the endpoint's stated window.

Why distinguish serious from other events?

Seriousness and severity are related but not interchangeable concepts. A serious-event classification concerns specified consequences or regulatory criteria, while severity describes how intense an event is. The registry says adverse events were described using Common Terminology Criteria for Adverse Events, version 3, and presents serious and other event counts. The detailed terms and their grades are not reported in the result details. The counts cannot therefore indicate which event types or severity levels account for the reported participants.

What can a confidence interval add?

In general, a confidence interval communicates uncertainty around an estimate: it gives a range of values compatible with the data and the method used to construct the interval. A narrow interval generally indicates greater precision than a wide interval, subject to the assumptions of the method. The registry record does not report confidence intervals for these safety counts. No interval should be inferred from the posted counts alone in this explanation.

General statistical methods for proportions can be used to describe uncertainty around participant event counts, but different methods behave differently when event counts are small or when no events are observed. A zero observed count is not evidence that the underlying event probability is exactly zero. The posted results provide no interval calculation or model-based estimate, so the appropriate interpretation remains descriptive.

Why does study design matter?

Randomization is a method for assigning participants to interventions so that, on average, differences in participant characteristics are less likely to systematically determine treatment group. This study is explicitly non-randomized. Its parallel groups are organized by cancer type, and the registry cautions against treating them as a like-for-like control comparison. Descriptive differences between those groups cannot be attributed to a treatment contrast using the information reported.

Masking can reduce the influence of knowledge about treatment assignment on assessment or reporting. The registry reports no masking. That fact does not establish that adverse-event reporting was biased, but it means the record does not describe masking as a safeguard. Further details about outcome assessment procedures are not reported in the registry record.

What is not available for statistical review?

The registry lists three outcome measures and no analyses. It does not report a statistical analysis plan, confidence intervals, hypothesis tests, adjusted models, interim analyses, or missing-data procedures in the registry record for this analysis. Those methods should not be assumed. The sample-size assumptions field describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the illustration uses a stated fraction of the observed effect; time-to-event calculations use a total event count, while other calculations use participants per arm. The record does not give numerical planning results in the registry record. Such illustrations are planning calculations, not observed power, and they do not supply evidence that the trial was designed or analyzed according to those assumptions.

Over-dispersion is a general statistical issue that arises when count variability exceeds what a simple model assumes. It can affect standard errors and uncertainty estimates for event counts. The registry does not report a count model or dispersion estimate for this outcome, so over-dispersion cannot be assessed from the posted information. Given the endpoint and the absence of listed analyses, the safest reading is to treat the event counts as descriptive observations rather than model-based estimates.

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("Metastatic Melanoma", "Other Metastatic Cancers")
n      <- c(2, 9)
events <- c(2, 9)
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  Metastatic Melanoma  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  Other Metastatic Cancers  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures, including the primary adverse-event measure and a secondary outcome concerning in vivo survival of T-cell receptor gene-engineered cells. It lists no analyses. The record does not report a multiplicity strategy describing how conclusions across outcomes or repeated statistical tests would be controlled. Without a reported analysis plan, it is not possible to determine whether outcomes were tested inferentially or how any such testing would have been interpreted.

Missing-data handling is also not reported in the registry record. The adverse-event entries give at-risk counts for each group, but the record does not explain whether participants with incomplete follow-up were excluded, how incomplete event reporting was handled, or whether any imputation was used. The outcome reporting window is specified, but that does not itself explain how missing observations within the window were treated.

The analysis populations are not defined beyond the group-specific at-risk counts included with the adverse-event results. No intention-to-treat, per-protocol, or safety-population definition is reported in the registry record for this analysis. The relationship between the enrollment figure and the outcome-specific at-risk counts is not explained. These omissions limit assessment of the population to which the counts apply and of the potential influence of missing information.

These are reporting gaps, not evidence that a particular procedure was or was not used. The registry record does not support assumptions about multiplicity adjustment, missing-data methods, analysis populations, or the handling of participants who did not contribute to a specific outcome.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event entries report 0 of 2 participants at risk in the metastatic melanoma group and 0 of 9 in the other metastatic cancers group. The other adverse-event entries report 2 of 2 and 9 of 9, respectively. These are participant counts, not counts of event episodes. The record does not provide detailed event terms in the registry record for this analysis.

A zero serious-event count means that no serious events were reported among the participants counted at risk in that group during the stated reporting period. It does not show that the underlying risk is zero or rule out serious events in other participants or settings. Conversely, the other-event counts do not indicate that all reported events had the same severity or clinical importance. Seriousness and severity classifications are not interchangeable.

The groups represent different cancer categories in a non-randomized study. Their event counts are descriptive and are not a comparative estimate of treatment safety between randomized arms. The record does not provide confidence intervals or a statistical comparison for these safety figures.

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

The result offers a limited account of adverse events recorded during a defined treatment-related period in a small, non-randomized phase 2 study. It reports serious and other adverse-event participant counts separately for the metastatic melanoma and other metastatic cancer groups. The counts describe what was recorded for those groups; they do not establish how often comparable events would occur in a broader population.

The reported zero serious events in the at-risk groups should not be interpreted as proof that serious adverse events are impossible. Small observed counts leave substantial uncertainty about uncommon outcomes, and no confidence intervals or inferential analyses are reported. The other-event counts show that participants in both groups were recorded as having other adverse events, but the registry entries do not identify the specific events, their severity grades, or whether event patterns were similar.

Because the groups were defined by cancer type and the allocation was non-randomized, their counts cannot serve as a controlled comparison of the intervention against another treatment. The record does not report a separate comparator treatment. It also does not provide an efficacy estimate for the primary endpoint, which is a safety outcome. Although the registry lists a secondary measure concerning engineered-cell survival, its numerical findings are not reported in the registry record.

Accordingly, the posted results can support a descriptive statement about the recorded adverse-event counts and their stated reporting period. They cannot establish a causal treatment effect, show that the regimen is effective or ineffective, or quantify safety beyond the reported participants and outcome definitions. Missing detail about analysis populations and missing-data procedures further limits interpretation.

14. Why This Trial Matters Statistically

This study illustrates why the statistical meaning of a result depends on its design and endpoint, not just on the reported counts. The primary measure is a participant count for adverse events, and the registry reports safety entries for groups defined by cancer type. Those data can describe events recorded in the study, but they do not create a randomized treatment contrast. Treating the groups as if one were a control group would give the counts a meaning the design does not support.

The study also highlights the importance of reporting the denominator and population definition alongside an event count. The registry gives at-risk counts for each group, but does not explain how those populations relate to the enrollment figure. Without explicit analysis-population and missing-data definitions, it is harder to assess exactly who contributed to each result.

Finally, a zero count is a useful observation but not a complete statement about risk. Statistical uncertainty matters especially when event counts are limited. Confidence intervals and a clearly described analysis could help communicate uncertainty, but none are reported for these results. The registry's presentation therefore emphasizes the distinction between what was observed and what can be inferred.

These are broadly relevant considerations in clinical biostatistics: match interpretation to the design, keep descriptive safety findings distinct from efficacy evidence, and make uncertainty and analysis choices transparent. In this study, the available record permits a focused description of reported adverse-event counts, while leaving important questions about estimation and analysis unanswered.

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 is the non-randomized design. The groups are defined by metastatic cancer type, rather than by randomized assignment to treatment and control. Their adverse-event counts therefore cannot be interpreted as a causal comparison. The registry explicitly notes that the arms are not a like-for-like control comparison.

The enrollment is listed as 12, and the reported at-risk counts are limited. Counts based on small groups provide limited information about uncommon events and do not, on their own, precisely estimate event frequency beyond the recorded participants. The registry reports no confidence intervals or inferential analyses for these results.

The primary endpoint is a participant count, which does not describe the number of event episodes, event timing, duration, or the distribution of severity. The detailed adverse-event terms are not included in the result details, although the registry refers to a separate adverse event module. The relationship between enrollment and the group-specific at-risk counts is not explained.

The registry does not report the analysis population definitions, missing-data handling, multiplicity procedures, or a statistical analysis plan. It also does not report a numerical result for the secondary outcome concerning engineered-cell survival in the registry record for this analysis. These gaps prevent a fuller evaluation of estimation choices and outcome interpretation. Treatment schedule details beyond the brief description are also not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Study of Metastatic Cancer That Overexpresses P53 Using Lymphodepleting Conditioning Followed by Infusion of Anti-P53 TCR-Gene Engineered Lymphocytes — NCT00393029.
• Registry record last updated 2011-08-15; status last verified 2011-08.
• Results first posted 2011-08-05.
• 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

NCT00393029 is a completed, non-randomized phase 2 study of anti-p53 TCR-gene engineered lymphocytes for metastatic cancers that overexpress p53. The record lists enrollment of 12, a parallel model, and no masking. It describes groups with metastatic melanoma and other metastatic cancers, rather than a randomized control comparison.

The primary outcome is the number of participants with adverse events related to treatment components during the stated reporting period. The serious-event counts were 0 of 2 in the metastatic melanoma group and 0 of 9 in the other metastatic cancers group. Other adverse events were reported for 2 of 2 and 9 of 9 participants, respectively. The registry lists three outcome measures and no analyses.

The record does not report confidence intervals, missing-data methods, analysis-population definitions, or a statistical analysis plan in the registry record for this analysis. The safety results are descriptive and do not establish an efficacy effect or a controlled comparison.