Intratumoral Cisplatin for Resectable NSCLC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Intratumoral Cisplatin for Resectable NSCLC (NCT04809103), a non-randomized phase 1 study. The primary outcome is Rate of Dose Limiting Toxicity.

2. Clinical Question

The clinical question is therefore about dose finding and short-term toxicity, not whether intratumoral cisplatin improves cancer outcomes relative to another treatment. The registry lists major pathologic response as a secondary outcome, but does not report results for that outcome. It also does not report a comparison against usual care or another intervention. The posted information should be read as a limited account of a small, early-phase study: it describes the intended dose-escalation question and includes some adverse-event counts, but does not establish the primary endpoint findings.

3. Trial Design

The registry classifies this study as phase 1, non-randomized, unmasked, and sequential. Its brief description calls the dose escalation a 3+3 design. Participants were intended to receive intratumoral cisplatin at successive dose levels, with the 10 mg level described as the first dose level and the 20 mg level as the second. Delivery was planned during a single bronchoscopy with cone-beam CT confirmation. The stated primary objective was to identify the maximum tolerated dose.

The record lists enrollment as 6 and status as completed. Its posted adverse-event summary lists 3 participants at risk in each dose group. Those group counts describe the posted safety summary; they do not provide a primary-endpoint analysis or establish how the escalation decision was made. The registry does not report the dose-escalation decision rules, whether additional dose levels were considered, or the number treated at each level in the primary endpoint population.

Because allocation was not randomized, the dose groups should not be interpreted as randomized treatment arms. In a sequential escalation, later dose levels are part of a dose-finding process rather than a concurrent control comparison. Differences in observed counts between dose levels could reflect the small groups, the order of treatment, or other factors; the registry record does not provide data to assess those possibilities.

The listed study dates are a start date of 2021-03-08 and a primary completion date of 2025-10-01. The record does not report a protocol-level statistical analysis plan, interim-analysis procedures, or the rationale for the enrollment target. These details should not be inferred from the 3+3 description alone.

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

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 Rate of Dose Limiting Toxicity, measured over Within 2 weeks of delivery.

The primary endpoint is titled “Rate of Dose Limiting Toxicity.” It is measured in participants and is defined in relation to adverse events assessed using the Common Terminology Criteria for Adverse Events. The specified assessment window is within 2 weeks of delivery. In a dose-escalation study, this kind of endpoint is used to assess whether toxicity at a dose level is acceptable for further evaluation and to inform dose selection.

The registry record does not report the number of participants meeting the dose-limiting toxicity definition, an endpoint rate, or an analysis by dose level. Although the adverse-event summary includes counts for serious and other adverse events, those categories are not identified in the record as equivalent to the primary endpoint. The posted counts therefore cannot be substituted for the dose-limiting toxicity result. Nor does the record report the detailed event criteria or rules used to classify an event as dose-limiting beyond its reference to the Common Terminology Criteria for Adverse Events.

As general statistical context, a rate describes how often an outcome occurs in a defined group, while its interpretation depends on the outcome definition, observation window, and participants included. These details matter particularly in a small dose-finding study, where a single participant’s classification can materially affect the observed pattern. Without the primary endpoint counts and analysis, the registry record does not establish which dose, if any, met the study’s tolerability criterion.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting a dose-finding study starts with its objective. This study’s stated objective was to identify the maximum tolerated dose of intratumoral cisplatin. That is different from testing whether a treatment improves an outcome compared with a control. The registry describes a non-randomized, sequential design and a 3+3 dose escalation. In general, sequential dose-escalation designs use observed toxicity at a dose level to guide decisions about subsequent dosing. The registry record does not report the detailed decision rules used in this study, so no specific escalation algorithm or decision can be reconstructed from the summary.

The primary endpoint is the rate of dose-limiting toxicity within 2 weeks of delivery. For an endpoint expressed as a rate, interpretation depends on a clearly defined event, an observation period, and the group of participants included. The record identifies the event assessment as based on the Common Terminology Criteria for Adverse Events and gives the observation window. It does not report the primary endpoint counts, the analysis population, or further operational criteria for deciding which adverse events were dose-limiting. Those omissions prevent an independent reconstruction of the endpoint result.

General statistical explanation: an estimate describes the observed data, while a confidence interval describes uncertainty around an estimate under the assumptions of the analysis. With few observations, estimates are typically imprecise; a confidence interval can communicate that uncertainty more fully than a point estimate alone. No confidence interval for the primary endpoint is reported in the registry record. The posted serious and other adverse-event counts are descriptive and do not, by themselves, constitute a modeled estimate of the primary endpoint.

General statistical explanation: a hypothesis test addresses whether data are compatible with a specified null model, conditional on the assumptions used. A p-value is not the probability that a treatment works, nor does it measure the size or clinical importance of an effect. The registry record lists no analyses, so it does not report a primary endpoint test, a p-value, or an inferential comparison between dose levels. Given the non-randomized sequential design, a simple test between the dose groups would not turn them into randomized comparison groups.

Over-dispersion is a general concern when count data vary more than a chosen statistical model expects. In a clinical trial, event counts can be influenced by differences among participants, follow-up, or event definitions. A model that assumes less variation than the data contain may produce overly narrow uncertainty intervals. The registry record does not report an over-dispersion assessment or a model for the primary endpoint; no such method should be assumed. For the posted safety data, descriptive counts are the directly reported quantities.

Missing-data handling is another important part of endpoint analysis. In general, an analysis should state how participants with incomplete outcome information or events outside the assessment window are handled. The registry record does not report missing-data methods or primary endpoint completeness. It also does not report whether the primary analysis included all treated participants, only evaluable participants, or another defined population. These details matter in dose escalation because exclusion or incomplete follow-up can alter the apparent toxicity pattern.

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The description says that the effect to detect is a stated fraction of the observed effect. Such illustrations are not the study’s stated design rationale, and they are not observed power. The record does not report a sample-size justification for the trial itself. Because the study is sequential and non-randomized, assumptions such as equal allocation between arms may not describe how its dose-escalation design operated.

Finally, statistical interpretation must be kept separate from clinical conclusions. The record identifies a secondary outcome of major pathologic response but does not report its results. Neither that outcome nor the primary endpoint can be inferred from the adverse-event summary. The defensible reading is limited to the information explicitly posted: a defined dose-finding objective, the design labels, and the reported safety counts, alongside substantial gaps in the analysis 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("Intratumoral Cisplatin Arm")
n      <- c(6)
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  Intratumoral Cisplatin Arm  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists major pathologic response as a secondary outcome and identifies a primary endpoint of dose-limiting toxicity within 2 weeks of delivery. It does not report results for the secondary outcome or a statistical analysis plan specifying how multiple outcomes were handled. Multiplicity refers generally to the increased chance of finding an apparently notable result when several outcomes or comparisons are examined. Methods for addressing it depend on the prespecified questions and analysis plan; those details are not reported in the registry record. No adjustment method should therefore be assumed.

The record lists no analyses. It does not report a primary endpoint analysis population, participant-level outcome completeness, or methods for handling missing observations. Although enrollment is listed as 6 and the safety summary gives 3 participants at risk in each dose group, these entries do not establish the denominator used for the primary endpoint. The registry record also does not report whether all participants completed the stated assessment window.

As general statistical context, missing outcome information can affect both an estimate and its uncertainty, especially when the reasons for missingness relate to health status or treatment. Good interpretation requires knowing who was included, what information was available, and how incomplete assessments were treated. Those details cannot be recovered from the posted summary. The record also does not report interim analyses or stopping procedures beyond describing the study as sequential with a 3+3 dose escalation.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted safety summary reports zero serious adverse events among 3 participants at risk in the Intratumoral Cisplatin 10 mg group and zero among 3 at risk in the Intratumoral Cisplatin 20 mg group. It reports one other adverse event in each group and zero deaths in each group. These are counts, not estimates of comparative safety.

The record does not describe the other adverse events or state whether they were related to treatment, occurred within the primary endpoint window, or met the dose-limiting toxicity definition. Therefore, they should not be interpreted as primary endpoint events. The registry also does not report confidence intervals or a formal safety analysis. General statistical context: a zero count in a small group does not show that the underlying risk is zero; it indicates only that no event in that category appears in the posted summary. Since allocation was non-randomized and sequential, the groups are not like-for-like controls, and their counts should not be used to rank the dose levels.

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

The result that can be described from the registry record is limited. The study is marked completed and is described as a phase 1, non-randomized, sequential dose-escalation trial of intratumoral cisplatin for early-stage, resectable non-small cell lung cancer. The stated primary objective was to identify the maximum tolerated dose, and the primary endpoint was dose-limiting toxicity within 2 weeks of delivery. The record does not report the primary endpoint findings or an identified maximum tolerated dose.

The safety summary records zero serious adverse events and zero deaths in each posted dose group, and one other adverse event in each group. These observations describe the counts in the registry summary only. They do not demonstrate that serious toxicity is absent, do not establish the dose-limiting toxicity rate, and do not indicate whether the other events were treatment-related. The registry does not report the detail needed to connect those categories to the primary endpoint.

The findings also do not answer whether cisplatin improves cancer outcomes. Major pathologic response is listed as a secondary outcome, but its results are not reported. There is no randomized comparator, and the sequential dose groups are not equivalent to randomized treatment arms. Consequently, neither a causal treatment-effect comparison nor a conclusion about benefit can be drawn from the posted data.

General statistical context: early-phase dose-finding studies are designed to inform dose selection, and their conclusions depend on event definitions, follow-up, participant inclusion, and escalation rules. Here, the registry record does not report enough of the primary analysis to evaluate those elements. The posted counts should therefore be interpreted as a limited safety description, not as a complete account of the trial’s principal result.

14. Why This Trial Matters Statistically

This trial is statistically interesting because its central question is dose selection rather than a randomized comparison of clinical outcomes. That distinction determines what the data can support. A sequential escalation study can describe toxicity across planned dose levels and use those observations to guide dose finding, but its groups are not concurrent randomized controls. Their counts cannot be interpreted as unbiased comparative treatment effects.

The record also illustrates why endpoint definition and reporting are central to interpretation. It specifies dose-limiting toxicity, the Common Terminology Criteria for Adverse Events, and an assessment window within 2 weeks of delivery. Yet it does not report the primary endpoint counts or the resulting dose decision. Without those results, the stated objective cannot be assessed from the registry summary, even though some broader adverse-event counts are posted.

The small posted group counts make restraint particularly important. General statistical context: sparse data leave substantial uncertainty, and a lack of recorded events in a category does not establish that the event is impossible or that risk is absent. Reporting event definitions, analysis populations, and uncertainty estimates would help readers understand how much the observations can support.

The registry lists major pathologic response as a secondary outcome, but no result is reported. This further separates the stated dose-finding objective from questions about tumor response or clinical benefit. The study’s statistical importance lies in the design and in the reporting gaps that shape what can be concluded, rather than in evidence for a treatment effect.

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 of the registry record is that it does not report the primary endpoint result. The dose-limiting toxicity count, rate, and any identified maximum tolerated dose are not reported. Although the endpoint window and general event assessment standard are stated, the operational dose-limiting toxicity criteria are not described in detail.

The posted adverse-event summary is limited to serious events, other events, and deaths. It does not identify the other events, their severity, timing, attribution, or relationship to the primary endpoint. It also does not report uncertainty estimates or a formal safety analysis. These counts therefore cannot fill the gap in the primary endpoint reporting.

The study is non-randomized and sequential, so the dose groups are not like-for-like control groups. The registry does not report detailed escalation decisions, the full protocol rules, or whether the stated dose levels were the only levels considered. It also does not report a statistical analysis plan, the primary endpoint analysis population, missing-data handling, or interim-analysis procedures.

Enrollment is listed as 6, while the posted safety summary lists 3 participants at risk in each dose group. The record does not explain the relationship between those entries or give a primary endpoint denominator. Major pathologic response is listed as a secondary outcome, but its results are not reported. Finally, the registry provides no sample-size justification for the trial itself. These limitations restrict interpretation to the design description and the posted adverse-event counts; they prevent a complete assessment of the primary dose-finding question.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Intratumoral Cisplatin for Resectable NSCLC — NCT04809103.
• Registry record last updated 2026-02-06; status last verified 2025-10.
• Results first posted 2026-02-06.
• 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

The registry describes a completed phase 1, non-randomized, sequential dose-escalation trial of intratumoral cisplatin for early-stage, resectable non-small cell lung cancer. The stated objective was to identify the maximum tolerated dose. The primary endpoint was dose-limiting toxicity within 2 weeks of delivery, assessed using the Common Terminology Criteria for Adverse Events.

The record lists a 10 mg first dose level and a 20 mg second dose level, and describes the design as 3+3. Enrollment is listed as 6. The posted safety summary reports zero serious adverse events, one other adverse event, and zero deaths in each group, with 3 participants at risk in each group. The record does not report the primary endpoint results, an identified maximum tolerated dose, or results for the listed secondary outcome of major pathologic response. It also lists no analyses.