Celecoxib and Radiation Therapy in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Celecoxib and Radiation Therapy in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer (NCT00046839), a non-randomized phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose (MTD) of Celecoxib Combined With Radiation Therapy (RT).

2. Clinical Question

The trial examined celecoxib given with radiation therapy in patients with locally advanced non-small cell lung cancer. Its Phase I component focused on dose-limiting toxicity and identifying a maximum tolerated dose; the Phase II component used celecoxib with radiation therapy at the dose specified for that stage. The registry record describes two celecoxib dose levels in Phase I and a Phase II arm using the higher listed dose. It does not report a separate control group or a randomized comparison.

The stated rationale describes combining the treatments and studying the regimen in this patient population. That rationale is not itself evidence about treatment effects. The registry record does not report a comparative estimate of effectiveness, nor does it provide a primary-endpoint result that would establish which dose met the stated toxicity criterion.

3. Trial Design

NCT00046839 is listed as a completed Phase I/II trial sponsored by the Radiation Therapy Oncology Group. The registry lists enrollment of 21 and a start date of 2002-07, with primary completion on 2011-09. The study is classified as nonrandomized, unmasked, and single-group. These design labels matter: the listed dose regimens do not constitute a randomized comparison against a separate control treatment.

The Phase I regimen descriptions include celecoxib 200 mg twice daily and 400 mg twice daily with concurrent radiation therapy. Celecoxib was described as beginning 5 days before radiation therapy, with the morning dose timed 1-2 hours before radiation once radiation began. The descriptions state that celecoxib would continue for 2 years or until disease progression. Radiation therapy is described as 2 Gy daily, 30-33 fractions, 5 days per week for 6-7. The final schedule wording is incomplete in the registry description, so no additional unit should be inferred.

The Phase II arm is listed as celecoxib 400 mg twice daily with radiation therapy. The primary endpoint description specifies follow-up for at least 90 days from the start of radiation and assessment of treatment morbidity. The dose-escalation rule was based on dose-limiting toxicities: six patients were to be accrued at each dose level, and the rule determined whether escalation occurred or the preceding dose was declared the maximum tolerated dose.

The registry record lists two outcome measures but reports no analyses. It does not provide the number treated at each dose level, dose-specific endpoint results, or the final maximum tolerated dose. The total enrollment listing alone does not establish how participants were distributed among the dose levels or how many contributed to each outcome.

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:

Analysis population for the primary outcome, as defined in the registry: The first six eligible patients who started protocol treatment at each dose level.

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: Eligible patients who started protocol treatment.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of Celecoxib Combined With Radiation Therapy (RT), measured over Start of treatment to 90 days.

The primary endpoint is the maximum tolerated dose of celecoxib combined with radiation therapy. It is a dose-selection endpoint, not a direct measure of tumor response or survival. The registry describes assessment of treatment morbidity from the start of radiation through at least 90 days. A dose-limiting toxicity was defined as grade 3 or 4 nonhematologic toxicity, excluding nausea, vomiting, and alopecia, or grade 4 hematologic toxicity.

The endpoint uses a categorical rating: 0 means the dose is not the maximum tolerated dose, and 1 means it is the maximum tolerated dose. Under the stated rule, six patients were to be accrued at each dose level. If no more than three of the six experienced a dose-limiting toxicity, that dose level was considered acceptable and escalation proceeded by accruing six more patients at the next dose level. Otherwise, the preceding dose level, if any, would be declared the maximum tolerated dose. The selected dose would then be used for the Phase II arm.

This type of endpoint is used in dose-finding because the question is whether a dose meets a prespecified tolerability rule, rather than whether it is better than another treatment. The registry’s operating-characteristic statements describe the planned rule’s behavior under assumed toxicity rates; they are not observed trial results. The actual endpoint result, including whether a dose was declared the maximum tolerated dose, is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint and design are best understood as a dose-finding procedure. The purpose of such a procedure is to use observed toxicity at successive dose levels to guide escalation, rather than to estimate a treatment contrast against a randomized control group. In this study, the registry describes two celecoxib dose levels in Phase I and a Phase II arm at 400 mg twice daily with radiation therapy.

How does the dose-escalation rule work?

The registry states that six patients were to be accrued at each dose level. If no more than three of the six experienced a dose-limiting toxicity, the dose was considered acceptable and escalation proceeded by accruing six more patients at the next dose level. If that condition was not met, the preceding dose level, if any, would be declared the maximum tolerated dose. The Phase II arm was to use the maximum tolerated dose.

This rule converts observed toxicity counts into a dose decision. It does not mean that a dose is free of risk, nor does the label maximum tolerated dose imply that all patients experience the same outcome. It is a decision defined by the protocol’s threshold and observation period. The registry defines dose-limiting toxicity as grade 3 or 4 nonhematologic toxicity, excluding nausea, vomiting, and alopecia, or grade 4 hematologic toxicity. The described primary-endpoint follow-up is at least 90 days from the start of radiation.

What do the stated operating characteristics mean?

The registry says that, at a given dose, the probability of halting dose escalation when the true toxicity rate is 50% or higher is at least 66%. It also states that when the true dose-limiting toxicity rate is instead 20%, there is still a 10% probability of halting escalation at that dose level. These are design characteristics under the stated assumptions, not estimates from the participants enrolled in the trial. They describe how the rule is expected to behave across hypothetical repetitions of a study under those toxicity conditions. They do not report the probability that a particular dose was safe or the chance that a specific trial conclusion is correct.

In general, a rule based on a small number of observations can be sensitive to the outcomes of individual participants. The observed count at a dose is used to make a discrete decision, and the decision may not precisely estimate the underlying toxicity probability. That general limitation applies to dose-finding procedures; it should not be mistaken for a trial-specific finding about the accuracy of this study’s decision.

What is the role of a confidence interval?

In general, a confidence interval expresses uncertainty around an estimated quantity. For a toxicity proportion, it can show that a finite set of observed outcomes is compatible with a range of underlying rates. A narrow interval indicates greater precision under the model used; a wide interval indicates less precision. The registry record does not report a confidence interval for the primary endpoint or for dose-specific toxicity rates, so no trial-specific precision range can be described.

Similarly, a p-value, when reported, measures how unusual data would be under a stated null model. It is not a measure of clinical importance and does not give the probability that a hypothesis is true. The registry record lists no analyses, so it does not provide a primary-endpoint p-value or an inferential comparison to interpret.

How should planning illustrations be read?

Any sample-size illustrations associated with this record are planning illustrations, not observed study outcomes and not observed power. The stated assumptions for those illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a fraction of the observed effect. The instructions distinguish time-to-event illustrations, which give a total number of events using the Schoenfeld approach, from other illustrations, which give participants per arm.

These assumptions are separate from the trial’s stated dose-escalation design. The registry record does not report a sample-size justification for the original trial, and no numerical sample-size illustration results are included in the record details. A planning calculation based on an observed effect is not proof that the trial had adequate power, and it cannot substitute for a reported estimate with uncertainty.

Why does the study structure matter?

Randomization is a method for balancing both measured and unmeasured characteristics between treatment groups on average. This trial is listed as nonrandomized and single-group, with no masking. Consequently, comparisons across the listed dose regimens are not protected by random allocation. General statistical methods can adjust for measured differences, but the registry does not report such an adjusted analysis. The absence of a comparison group also means that an outcome observed during treatment cannot, by itself, establish what would have happened under another treatment or without the regimen.

For this record, interpretation should therefore start with the dose-finding question and the prespecified toxicity rule. Since the actual primary outcome and analyses are not reported in the registry record, the method can be explained, but its result and precision cannot be assessed.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and no analyses. It identifies maximum tolerated dose as the primary endpoint, but the details of the other outcome measure are not present in the record information. The registry does not report a multiplicity adjustment, a hierarchy for testing outcomes, or an analysis plan explaining how multiple endpoints or dose levels would be handled. It would therefore be inappropriate to claim either that multiplicity was controlled or that it was ignored in the trial’s actual analysis.

Multiplicity is a general concern when several hypotheses are tested: the chance of at least one apparently unusual result can increase as more tests are performed. Dose-finding has a different decision structure from a single confirmatory comparison, because dose escalation follows a prespecified rule. Even so, the registry does not provide enough analysis detail to determine whether additional outcomes or repeated decisions were incorporated into a formal statistical plan beyond the toxicity rule described.

The record identifies the primary endpoint population as the first six eligible patients who started protocol treatment at each dose level. It does not report the number who actually entered each dose level, how many met eligibility criteria, whether all were followed through the endpoint period, or how missing outcome data were handled. It also does not state whether the analysis used an intention-to-treat, treated, eligible, or other analysis population. These omissions limit assessment of who contributed to the endpoint and whether missing observations could have affected the dose decision.

In general, missing data can affect an estimate or decision when the chance of an outcome being missing is related to the outcome itself or to patient characteristics. The appropriate response depends on why data are missing and on the endpoint and analysis plan. The registry record does not describe those details, so the impact of missing data cannot be evaluated.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: supraventricular arrhythmias (svt/atrial fibrillation/flutter) (14.3%), infection without neutropenia (9.1%).

The registry lists serious adverse-event figures for two experimental regimen groups. For Phase I: Celecoxib 200mg BID + RT, the serious adverse-event fields list 7 at risk and 1 affected; the other adverse-event fields list 7 at risk and 7 affected. For Phase I/II: Celecoxib 400mg BID + RT, the corresponding fields list 11 at risk and 1 affected for serious adverse events, and 11 at risk and 8 affected for other adverse events. These are descriptive entries, not comparative estimates.

The registry also lists supraventricular arrhythmias (SVT/atrial fibrillation/flutter) at 14.3% and infection without neutropenia at 9.1% among the top serious adverse-event terms. The record information does not identify a dose-specific interpretation for these terms, so they should be read as listed rather than assigned to a particular regimen. Death values are not reported in the registry record.

“At risk” is the registry’s denominator field for each group; the counts should not be treated as a comparison of treatment effects. The groups were not randomly allocated as a like-for-like control comparison, and the record does not provide event timing, duration of observation by group, patient-level detail, or a statistical analysis of safety. Serious and other adverse-event categories also describe different classifications. These figures alone cannot establish whether an event was caused by treatment or whether one regimen was safer than another.

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

The record establishes that a Phase I/II study was registered to examine celecoxib with radiation therapy in locally advanced non-small cell lung cancer. Its primary question was dose selection based on treatment morbidity and a stated dose-limiting toxicity rule. The registry gives the rule and regimen descriptions, but it does not report the primary endpoint result. The maximum tolerated dose selected by the investigators is therefore not reported in the registry record.

The record does not establish that celecoxib plus radiation therapy improved tumor control, survival, symptoms, or any other clinical outcome. Those outcomes are not represented by the stated primary endpoint, which concerns dose tolerance. The trial’s rationale describes why the combination was studied, but a rationale is not a result. Nor does the record establish that the combination failed to meet an effectiveness or tolerability criterion; the relevant primary result is absent.

The adverse-event entries provide descriptive counts and listed serious-event terms. They do not give a randomized comparison or enough information to determine causality, relative safety, or the uncertainty around group-specific risks. The presence of a listed event does not alone show that the treatment caused it, and the absence of a listed count for another event does not prove that it never occurred.

Because the trial is nonrandomized and listed as a single-group model, it cannot be read as a controlled estimate of the effect of celecoxib or radiation therapy. The different dose regimens should not be treated as randomized alternatives. The registry does not report dose-specific primary outcomes, a participant flow by dose, an analysis population, or an adjusted comparison. The reported enrollment of 21 does not fill those gaps.

The most defensible interpretation is limited: the registry documents a planned dose-finding approach and some adverse-event summaries, while leaving the primary result and its precision unavailable. Readers can understand what decision rule was intended, but cannot verify the decision made, quantify the observed toxicity at each dose, or draw a conclusion about comparative effectiveness from the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why the statistical question must be matched to the study design. Its primary endpoint is a dose-selection decision based on toxicity, not a randomized estimate of treatment benefit. Reading a dose-finding study as though it were a controlled effectiveness trial would misstate what its design can answer.

The registry makes the decision rule explicit: a dose level was to be considered acceptable under a specified toxicity-count threshold, with escalation or a maximum-tolerated-dose decision following from that rule. The accompanying operating-characteristic statements are useful as descriptions of the planned rule under assumed toxicity rates. They are not a substitute for observed trial outcomes. Keeping design properties distinct from results is a basic but important statistical distinction.

The record also shows why result reporting is essential to interpretation. Without the observed dose-limiting toxicity counts, dose-specific participant numbers, final dose decision, and uncertainty, the reader cannot assess how the rule operated in practice. A completed status does not itself provide these results. Likewise, adverse-event summaries do not recover the missing primary endpoint or create a controlled comparison.

Finally, the classification as nonrandomized and single-group constrains what can be inferred across the listed regimens. Randomization is one way to support causal comparisons; its absence means that dose-group contrasts require particular caution. The registry does not report an adjusted analysis that might address measured differences. This makes clear why statistical interpretation depends on both the numbers reported and the design that produced them.

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 principal limitation for interpreting this record is that the primary endpoint result is not reported. The dose-finding rule is described, but the record does not state the observed dose-limiting toxicity counts, the final maximum tolerated dose, or whether the escalation rule led to the planned Phase II dose. No estimate of endpoint precision is reported.

The total enrollment listing is not broken down by dose, phase, or analysis population. The record does not report how many participants started treatment at each level, how many were eligible for the primary endpoint, or whether follow-up was complete. It therefore cannot establish whether the endpoint was assessed in the intended group of six at each dose level.

The study is classified as nonrandomized, unmasked, and single-group. No separate control group is listed, and the registry does not report a randomized comparison or an adjusted analysis. Differences across dose groups, if any, would not by themselves establish a causal dose effect. The registry also does not report baseline characteristics by regimen or enough details to evaluate possible differences in follow-up.

Although the record lists two outcome measures, it reports no analyses. The additional outcome’s details, multiplicity approach, handling of missing data, and analysis populations are not reported in the registry record. The record also does not provide confidence intervals or other uncertainty measures for the listed adverse-event summaries. Death figures are not reported in the registry record.

These limitations do not demonstrate that the study’s conduct or analysis was inadequate; they describe what cannot be assessed from the registry record. In particular, absence of results in this record should not be interpreted as evidence that the trial did not observe an outcome.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Celecoxib and Radiation Therapy in Treating Patients With Locally Advanced Non-Small Cell Lung Cancer — NCT00046839.
• Registry record last updated 2015-11-17; status last verified 2015-11.
• Results first posted 2014-03-17.
• 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.

18. Record Summary

NCT00046839 is a completed, nonrandomized Phase I/II study of celecoxib combined with radiation therapy for locally advanced non-small cell lung cancer. The registry lists enrollment of 21 and identifies maximum tolerated dose as the primary endpoint. Phase I included listed celecoxib doses of 200 mg twice daily and 400 mg twice daily with radiation therapy; the Phase II regimen listed 400 mg twice daily with radiation therapy.

The primary endpoint description defines dose-limiting toxicity and gives an escalation rule based on six patients at each dose level. The registry lists two outcome measures but no analyses. It does not report the observed primary endpoint result, final maximum tolerated dose, dose-specific toxicity counts, or uncertainty estimates. Serious and other adverse-event summaries are listed for the two regimen groups, but the study design does not support treating them as a randomized comparison.

The registry record supports describing the planned dose-finding question and its decision rule. It does not support a conclusion about comparative effectiveness or identify the dose selected from the trial results.