ZD1839 (Iressa) for Recurrent or Metastatic Squamous Cell Carcinoma of the Skin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ZD1839 (Iressa) for Recurrent or Metastatic Squamous Cell Carcinoma of the Skin (NCT00054691), a na phase 2 study. The primary outcome is Number of Participants With Objective Response (Partial Response, Stable Disease and Progressive Disease).

2. Clinical Question

The study's stated goal was to learn whether ZD1839 could shrink or slow cancer growth and to study safety in this population. The primary outcome is titled as the number of participants with objective response, with Partial Response, Stable Disease and Progressive Disease named in parentheses. The registry record supplies definitions for these categories, but does not report the participant count in any category or a combined primary response result. It also does not explain how the three named categories contribute to a single objective-response count.

Because the design has no concurrent comparator, the question is descriptive: what response classifications and safety events were recorded among participants receiving Iressa? The record does not support a direct comparison with another treatment or a conclusion that separates treatment effects from the natural course of disease and other influences.

3. Trial Design

This is a phase II, single-group study sponsored by M.D. Anderson Cancer Center. It is recorded as completed, with enrollment of 40 participants. The registry lists the start as 2004-05 and primary completion as 2012-10. The study concerns recurrent or metastatic squamous cell carcinoma of the skin, also described in the record as Skin Cancer.

All participants were assigned to the Iressa (ZD1839) intervention, described as 250 mg by mouth daily. The record lists allocation as NA and masking as none. There is no control arm, randomized comparison, or like-for-like treatment contrast. Consequently, any response or adverse-event count is a description of participants in this study rather than a comparative estimate of treatment effect.

The primary outcome concerns participant response, assessed according to UICC/WHO criteria. Assessments were scheduled every 8 weeks until disease progression. Duration of Response is listed as a secondary outcome. The record does not specify the assessment schedule or analysis details for that secondary outcome beyond its name.

The registry notes that 2 participants had unmeasurable disease and 1 was noncompliant. It does not describe how these participants were handled in the primary analysis or identify a prespecified analysis population. No statistical analyses are listed in the registry record. A sample-size justification, interim-analysis plan, and detailed statistical plan are not reported in the registry record. The study's completion status and enrollment do not, by themselves, establish how many participants contributed evaluable response data.

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: Out of 40 participants, 2 participants had unmeasurable disease and 1 participant was noncompliant.

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: Out of 40 participants, 2 participants had unmeasurable disease and 1 participant was noncompliant.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Objective Response (Partial Response, Stable Disease and Progressive Disease), measured over Every 8 weeks till disease progression..

The primary outcome is a participant count associated with response classification. The registry describes assessment using UICC/WHO criteria and specifies partial response, stable disease, and progressive disease. Partial response applies only to participants with at least one measurable lesion and is defined as at least 50% decrease from baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable disease means no progression of evaluable disease and/or no new lesions. Progressive disease is defined by an increase in lesion measurements, using the stated threshold rule, or clear worsening of any evaluable disease.

Response classification is used in clinical studies to describe how disease status changes or remains stable during observation. A count can communicate how many participants fall into specified categories, but its interpretation depends on clear category definitions, the population assessed, and how unavailable or unevaluable assessments are handled. In this record, the outcome title names objective response alongside partial response, stable disease, and progressive disease. The definitions are present, but the record does not clarify how those classifications were combined for the stated primary count.

No primary response count or category-specific results are reported in the registry record. The scheduled assessment timeframe is every 8 weeks until disease progression.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry is limited. It identifies a single-group design, a participant-count primary outcome, response criteria, an assessment timeframe, and a secondary outcome. It does not report a statistical analysis or the primary outcome result. The concepts below explain how these features are usually interpreted; they do not describe unreported procedures from this study.

What a participant count represents

A count reports how many participants meet a defined condition. For a response outcome, that condition must be explicit: for example, a count might refer to a particular response category or to a prespecified combination of categories. The registry gives criteria for partial response, stable disease, and progressive disease, but the primary outcome title groups the categories in a way that does not clarify the intended combined count. The category definitions alone cannot establish which participants were included in the primary result.

In general, counts are easier to interpret when accompanied by the analysis population and a denominator. A denominator indicates how many participants were assessed for the outcome; the analysis population explains who was included and why. Although enrollment is 40, the record notes unmeasurable disease for 2 participants and noncompliance for 1. It does not report a denominator for the primary result or explain how these participants were handled. No percentage or rate should be inferred without a stated denominator and result.

Response criteria and assessment timing

The record says that response was assessed according to UICC/WHO criteria every 8 weeks until disease progression. The criteria refer to measurable lesions and changes from baseline, and distinguish partial response, stable disease, and progressive disease. In general, standardized criteria can make response classification more consistent by defining what counts as a change. Consistency also depends on the assessment process and on how missing, unevaluable, or discordant assessments are handled. Those operational details are not reported in the registry record.

The progressive-disease definition includes an increase in lesion measurements, with a threshold based on the smaller of the specified alternatives, or clear worsening of evaluable disease. The record also defines stable disease in relation to progression and new lesions. These definitions describe classification rules; they are not study results. The registry does not provide the number of participants meeting each rule.

Precision and uncertainty

In general, a point estimate gives a single summary of an outcome, while a confidence interval communicates uncertainty around that estimate under a specified statistical approach. For a participant count or proportion, precision depends on the observed result and the number of participants included in the analysis. No primary count, denominator, confidence interval, or other uncertainty measure is reported in the registry record, so the precision of a response estimate cannot be evaluated.

General statistical explanations of uncertainty should not be confused with observed findings. A planning calculation is not a result from participants, and sample-size illustrations are not observed power. The registry's stated planning assumptions describe 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 study itself is single-group. The numerical planning outputs and the effect value used for those illustrations are not reported in the registry record; the assumptions do not change the actual design or provide evidence of a comparative effect.

Secondary outcome and time-to-event interpretation

Duration of Response is listed as a secondary outcome. In general, a duration outcome concerns how long a response persists, and its analysis may need to account for participants whose response duration is not fully observed. Such methods depend on definitions of response onset and end, follow-up, and censoring. The registry record does not report the duration result or the analysis methods and censoring rules used for it. No duration estimate should be inferred from the outcome name alone.

What the analysis record can establish

The registry lists no analyses. That absence means the record does not document a statistical test, model, adjustment, or interval estimate for the posted outcome information. It does not establish which methods may have been used outside the registry. A full interpretation would require reported results, analysis populations, missing-data handling, and a clear mapping between the response categories and the primary endpoint. Those details are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies 2 outcome measures: the primary participant response count and the secondary outcome Duration of Response. When a study examines multiple outcomes, general statistical practice considers whether the analyses are prespecified and whether any adjustment or interpretive strategy addresses the possibility of chance findings across multiple tests. No analyses are listed, and a multiplicity plan or adjustment is not reported in the registry record. It is therefore not possible to determine whether multiplicity was addressed or how it would affect interpretation.

Missing and unevaluable data require separate attention. The record says that 2 participants had unmeasurable disease and 1 was noncompliant. It does not say whether these participants were excluded, counted in a category, treated as having no response, or handled in another way. Nor does it report the number with completed response assessments, the amount of missing data, or a sensitivity analysis. The enrollment count should not be assumed to be the primary analysis denominator.

The registry does not name an intention-to-treat, per-protocol, or other analysis population. Those labels cannot be assigned based on enrollment and the limited notes about disease measurability and compliance. The analysis population, exclusions, and reasons for any exclusions are not reported in the registry record.

For Duration of Response, follow-up and censoring rules would be important to understand in general, because not every participant's response duration may be observed in full. The registry does not provide those rules or a result. As no analyses are listed, the record also does not document how missing response assessments or incomplete follow-up were addressed statistically.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pulmonary embolism (7.5%), deep vein thrombosis (legs) (5.0%), hepatic function disorder (5.0%), interstitial pneumonia (5.0%), abdominal pain (2.5%).

The safety record lists 40 participants at risk for serious adverse events and 17 participants affected. It also lists 40 participants at risk for other adverse events and 40 affected. These counts describe the registry's recorded safety groups; the record does not provide a safety assessment timeframe or further analysis details. The deaths field is not reported in the registry record.

The serious adverse event terms listed with percentages are Pulmonary Embolism, 7.5%; Deep Vein Thrombosis (Legs), 5.0%; Hepatic Function Disorder, 5.0%; Interstitial Pneumonia, 5.0%; Abdominal Pain, 2.5%; and Intestinal Ischaemia, 2.5%. These are event-term percentages, not a comparative estimate. The record does not state whether participants could contribute more than one term, so the terms should not be treated as mutually exclusive categories or added together.

In general, adverse-event counts describe events recorded during a study and do not by themselves establish cause. Here, the single-group design provides no concurrent comparator for interpreting differences in safety outcomes. The registry record does not report event timing, severity grading beyond the serious-event classification, duration, or statistical comparisons. The listed figures should therefore be read as descriptive safety information for the study group, not as estimates of relative risk.

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

The record establishes that 40 participants were enrolled in a single-group phase II study of Iressa (ZD1839), taken by mouth at 250 mg daily, for recurrent or metastatic squamous cell carcinoma of the skin. It describes response criteria, assessment every 8 weeks until disease progression, a secondary Duration of Response outcome, and adverse-event counts and terms.

It does not report the primary response count, category-specific response results, a response estimate with uncertainty, or the result for Duration of Response. Therefore, the registry record cannot show how many participants experienced any particular response classification or how precisely that outcome was estimated. The primary outcome title also does not clarify how the named response categories contribute to a single count.

The study has no comparator group. In general, outcomes in a single group cannot isolate the effect of an intervention from other influences, because the record does not show what would have happened to similar participants under another treatment or without the intervention. The study's design should not be read as a randomized or controlled comparison.

The safety figures are descriptive counts for the study group. They do not, by themselves, establish that the intervention caused an event, and the record lacks a comparator for estimating relative safety. The 2 participants with unmeasurable disease and 1 noncompliant participant make analysis-population information particularly relevant, but their handling is not described.

These limits do not negate the descriptive role of a phase II study. They define what can and cannot be concluded from the registry record: the design and outcome definitions are documented, while the primary efficacy result and key analysis details are not reported in the registry record. No conclusion about treatment benefit or lack of benefit follows from an outcome result that is absent.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a reported result are both needed for statistical interpretation. The record gives response criteria and assessment timing, but does not report the primary count. It also names partial response, stable disease, and progressive disease in the endpoint title without explaining how they form the stated objective-response measure. A reader needs both the classification rule and the observed category counts to understand what the endpoint says.

The study also shows the limits of interpreting a single-group result. Participant counts can describe what occurred in the enrolled group, but without a comparator they do not provide a direct estimate of how outcomes differ under another treatment. This is a design limitation, not a flaw that can be repaired by a statistical calculation after the fact.

Missing analysis-population details are another statistical concern. The record notes unmeasurable disease for 2 participants and noncompliance for 1, yet does not say how these cases were treated in the response analysis. Reporting the analysis population and the handling of unavailable assessments is important because different choices can change the meaning of a count.

Finally, the registry includes safety counts and serious-event terms but no comparative safety analysis or event timeframe. These data are descriptive and should be interpreted within that scope. The study is a useful example of how design, endpoint definition, missing-data handling, and transparent results reporting jointly determine the strength and limits of a clinical trial's statistical conclusions.

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 interpretation is that the primary outcome result is not reported in the registry record. There is no participant count by response category, no stated denominator for the primary outcome, and no reported precision measure. The endpoint title also groups objective response with partial response, stable disease, and progressive disease without clarifying the intended combined count.

The single-group design has no concurrent comparator. It can describe outcomes among participants receiving Iressa, but does not directly estimate a contrast against another treatment or a control condition. Allocation is listed as NA and masking as none. No statistical adjustment can create a randomized comparison that the design did not include.

The registry reports that 2 participants had unmeasurable disease and 1 was noncompliant but does not describe their inclusion in analyses. The analysis population, missing-assessment rules, reasons for any exclusions, and sensitivity analyses are not reported in the registry record. These omissions prevent assessment of how incomplete or unevaluable information may affect the response summary.

Although Duration of Response is listed as a secondary outcome, its result and analysis details are absent. Follow-up and censoring rules for that outcome are not reported in the registry record. The safety information gives participant counts and selected serious-event terms, but does not report the safety timeframe, event-level details, or a comparator-based analysis. The deaths field is also not reported.

No analyses are listed in the registry record. A statistical plan, sample-size justification, interim-analysis plan, and multiplicity approach are not reported in the registry record. These limitations mean that the statistical strength and precision of the study's response findings cannot be assessed from the record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: ZD1839 (Iressa) for Recurrent or Metastatic Squamous Cell Carcinoma of the Skin — NCT00054691.
• Registry record last updated 2015-03-13; status last verified 2015-02.
• Results first posted 2015-02-12.
• 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

NCT00054691 is a completed phase II, single-group study sponsored by M.D. Anderson Cancer Center. It enrolled 40 participants with recurrent or metastatic squamous cell carcinoma of the skin. The intervention was Iressa (ZD1839), 250 mg by mouth daily. The record lists no masking and no comparator group.

The primary outcome is a participant response count assessed every 8 weeks until disease progression using UICC/WHO criteria. Duration of Response is listed as a secondary outcome. The registry notes that 2 participants had unmeasurable disease and 1 was noncompliant. It records serious adverse events in 17 of 40 participants at risk and other adverse events in 40 of 40 at risk.

The primary response count, duration result, analysis population, and statistical analyses are not reported in the registry record. The available information describes the study design, outcome definitions, and selected safety data, but does not provide an efficacy result or a comparative treatment estimate.