AZD0530 in Treating Patients With Extensive Stage Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for AZD0530 in Treating Patients With Extensive Stage Small Cell Lung Cancer (NCT00528645), a na phase 2 study. The primary outcome is Progression-free Survival Rate at 12 Weeks.

2. Clinical Question

The study was intended to assess a short-term disease-status outcome after treatment began. It was a phase II study sponsored by the National Cancer Institute (NCI), with enrollment of 23 participants. The registry describes periodic blood sampling for defined translational studies of circulating tumor cell levels, but the primary question concerns progression-free survival at the specified time point.

The registry record does not report a numerical estimate for the primary endpoint, its 95% confidence interval, or a result for the listed secondary outcomes. It therefore does not establish, from the posted results, how many evaluable participants met the endpoint or how precisely that percentage was estimated. The study design also does not support a direct treatment-versus-control comparison because no control group is listed.

3. Trial Design

This was a phase II, single-group study of AZD0530 in extensive-stage small cell lung cancer. The official title describes treatment after four cycles of cytoreductive chemotherapy. The study enrolled 23 participants and is recorded as completed. Its start is listed as 2007-11 and its primary completion as 2008-11.

Participants received oral AZD0530, identified in the intervention record as saracatinib, once daily for up to 2 years, unless disease progression or unacceptable toxicity occurred. The treatment description also notes blood samples at baseline and periodically during the study for defined translational studies of circulating tumor cell levels. Masking is listed as none. Allocation is recorded as not applicable, and the model is single group. There is no concurrent control arm or randomized treatment assignment described.

The primary outcome is progression-free survival rate at 12 weeks. The registry defines the measure as the percentage of evaluable participants who are alive and progression-free at 12 weeks after registration. Eligibility, consent, starting AZD0530, and not being lost to follow-up before the 12-week assessment are part of the stated evaluability definition. RECIST v1.1 criteria are used to define progression.

Listed secondary outcomes are overall survival, confirmed tumor response, and progression-free survival. Confirmed tumor response is defined as complete or partial response on consecutive evaluations at least 4 weeks apart. The registry record lists four outcome measures in total, but does not give numerical results for these outcomes. It also does not report details of a statistical analysis plan, the study's sample-size justification, or interim analyses.

Because the design is single group, observations describe outcomes among participants treated in this study. Without a concurrent comparison group, differences attributable to treatment cannot be separated from other influences using this design alone. The enrollment count and design features describe how the study was conducted; they are not evidence of the primary endpoint result.

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.

Before assignment: One patient cancelled prior to treatment initiation and is excluded in the analysis.

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 Progression-free Survival Rate at 12 Weeks, measured over 12 weeks.

The primary endpoint is the progression-free survival rate at 12 weeks. It is a fixed-time measure: the registry defines it as the percentage of evaluable participants who are both alive and progression-free 12 weeks after registration. The denominator is the evaluable population described in the record, not necessarily every person enrolled. Participants who meet eligibility criteria, sign consent, begin AZD0530, and are not lost to follow-up before 12 weeks are considered evaluable under that definition.

Progression is assessed using RECIST v1.1. The record identifies progression as a new lesion or at least a 20% increase from baseline in the sum of the longest diameter of target lesions. Thus, the endpoint combines survival status and tumor-progression status at the stated assessment time. A participant who has progressed by that time does not meet the endpoint, even if alive; a participant who has died also does not meet it.

A fixed-time rate gives a clinically interpretable snapshot of the proportion meeting a defined status at a particular time. In general, such a measure can be useful when the study question concerns short-term disease control, but it does not describe the entire timing pattern of progression or death. The registry record does not report the estimated rate or its 95% confidence interval, so the observed level and precision cannot be assessed from the posted results. It also does not report how the endpoint estimate was calculated beyond the stated numerator and denominator definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a proportion at a fixed time point. The registry defines the numerator as participants who are alive and progression-free 12 weeks after registration, and the denominator as participants considered evaluable under the stated criteria. The result would be expressed as a percentage of participants. The registry record does not report the percentage itself, the numerator, or the evaluable denominator.

What does the 95% confidence interval describe?

In general, a confidence interval communicates uncertainty around an estimated quantity. For a percentage, it gives a range of values compatible with the observed data under the statistical method and assumptions used. A wider interval indicates less precision, while a narrower interval indicates greater precision. The registry identifies a 95% confidence interval as the dispersion measure for the primary endpoint, but does not report its limits or state the method used to calculate it. Precision therefore cannot be evaluated from the posted results.

A confidence interval is not a guarantee that a treatment effect lies within a particular range, and it does not by itself establish a causal effect. For this single-group study, an interval around the 12-week rate would describe uncertainty in the rate estimated for the evaluable participants under the analysis method. It would not replace a comparison with a control group.

Why distinguish a fixed-time rate from a time-to-event analysis?

In general, a fixed-time rate classifies participants according to their status at a particular assessment time. A time-to-event analysis instead uses information about when an event occurs and may account for different lengths of follow-up, depending on the method. The registry names progression-free survival both as a primary rate at 12 weeks and as a secondary outcome, but does not report the secondary outcome's analysis method or time-specific results. It would be inappropriate to assume that a Kaplan–Meier method or another particular time-to-event method was used.

The endpoint's evaluability definition matters because the denominator is not automatically the full enrollment. Participants must satisfy the listed eligibility, consent, treatment-start, and follow-up conditions. In general, changing the denominator or handling of unavailable outcome assessments can affect a proportion. The registry record does not report the evaluable count or a detailed missing-data method, so the impact of unavailable assessments cannot be judged.

How should the design shape statistical interpretation?

In general, random assignment and a concurrent comparison group help separate treatment differences from other differences between participants and from changes over time. This study is listed as single group, with allocation not applicable and no masking. The record therefore describes outcomes in the treated group, not a randomized estimate of a treatment contrast. A percentage or confidence interval, even if reported, would not by itself resolve that design limitation.

The registry identifies a phase II study and enrollment of 23. It does not report the protocol's sample-size justification or the statistical plan. Planning illustrations based on an observed effect are not the trial's own design justification or an observed-power analysis. The stated planning assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a specified share of the observed effect. Those assumptions describe a planning exercise, not the single-group design recorded for this study. They should not be read as the actual trial's allocation, as evidence that the trial achieved a particular power, or as a reported treatment result. No calculated sample-size values are reported in the registry record.

Over-dispersion is a general concern when observed variability exceeds what a simple statistical model assumes. In general, ignoring it can make uncertainty appear smaller than it is. The registry record does not report an over-dispersion assessment or enough analysis detail to determine whether such an issue applied. Similarly, the specific confidence-interval procedure, covariate adjustment, and handling of repeated assessments are not reported in the registry record. These omissions prevent reconstruction of the analysis from the record alone.

The listed secondary outcomes address survival and tumor response, but their numerical results and analysis details are not reported. General statistical practice recognizes that interpreting multiple outcomes can raise multiplicity concerns, because looking across outcomes may increase the chance of highlighting an apparently notable result. Whether multiplicity was addressed, and by what procedure, is not reported in the registry record. No adjustment or unadjusted significance test should be attributed to this study based on the information recorded.

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("Treatment (Saracatinib)")
n      <- c(23)
events <- c(6)
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  Treatment (Saracatinib)  23  6  26.1  10.2  48.4  12.5  46.5  12.6  46.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and three secondary outcomes: overall survival, confirmed tumor response, and progression-free survival. The record describes the primary endpoint as a 12-week progression-free survival rate. Confirmed tumor response requires complete or partial response on consecutive evaluations at least 4 weeks apart. Numerical findings for the primary and secondary outcomes are not reported.

When multiple outcomes are examined, general statistical practice considers whether the analysis plan accounts for the number of questions being tested. Without that information, the chance of a misleading finding across multiple analyses cannot be assessed. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or whether any outcome analyses were adjusted. It also records no analyses, so there are no posted analysis results from which to infer an adjustment approach.

The primary endpoint definition states that evaluable participants must not be lost to follow-up before 12 weeks. This addresses who is included in the endpoint population, but it does not fully describe how missing assessments or other incomplete data were handled. The number of participants who were evaluable, lost to follow-up, or otherwise missing endpoint information is not reported in the registry record. Nor is a sensitivity analysis for missing data reported.

The registry record also does not report the analysis population for the secondary outcomes, rules for censoring, or procedures for handling treatment discontinuation. Those details can affect the interpretation of outcome estimates, particularly when follow-up differs across participants. They cannot be inferred from the primary endpoint definition. Accordingly, the population and missing-data basis for any unreported result remain unclear.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: platelet count decreased (13.0%), nausea (8.7%), vomiting (8.7%), edema limbs (8.7%), dyspnea (8.7%).

The registry lists 23 participants at risk for serious adverse events and 23 at risk for other adverse events in the saracatinib treatment group. It records 6 participants as affected by serious adverse events and 22 as affected by other adverse events. These are separate categories in the record; they should not be added together as if they represented distinct participants.

The listed serious adverse-event terms and percentages are platelet count decreased, 13.0%; nausea, 8.7%; vomiting, 8.7%; edema limbs, 8.7%; dyspnea, 8.7%; and hemoglobin decreased, 4.3%. These percentages are reported as event-term frequencies. The registry record does not provide additional detail on whether participants experienced more than one listed term, nor does it identify the denominator used for each term's percentage in the information recorded.

Adverse-event figures describe events recorded during the study; they do not establish that the study drug caused every event. General interpretation also depends on event definitions, duration of observation, severity, and comparison with another group. A concurrent control group is not listed, so these figures do not provide a randomized safety comparison. Deaths are not reported in the registry record; that absence should not be interpreted as evidence that no deaths occurred.

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

The record establishes that AZD0530 was studied in a phase II, single-group setting after four cycles of cytoreductive chemotherapy in patients with extensive-stage small cell lung cancer. It defines a primary endpoint based on the percentage of evaluable participants who were alive and progression-free 12 weeks after registration. It also specifies the RECIST v1.1 progression criteria and lists secondary outcomes and selected adverse-event information.

The record does not report the primary endpoint percentage or its 95% confidence interval. It therefore does not show the observed 12-week progression-free survival rate or how precisely that rate was estimated. Numerical results for overall survival, confirmed tumor response, and the other progression-free survival outcome are also not reported. The listed safety counts and event terms do not substitute for those efficacy results.

Even if a single-group outcome estimate were available, this design would describe the treated participants rather than show what would have happened to comparable participants under another treatment. Without a concurrent control group, the study cannot by itself separate treatment effects from other possible influences on outcomes. It is therefore important not to interpret the study design or the treatment rationale as evidence that AZD0530 did or did not produce a benefit.

The entry also does not report the statistical analysis plan, the sample-size justification, the missing-data strategy, or a multiplicity approach. Those details would help readers assess how results were planned and analyzed. Their absence from the registry record limits interpretation but does not establish that the procedures were absent from the full study protocol.

The most defensible reading is descriptive: the registry documents a completed study, its treatment schedule and endpoint definition, and selected safety-event figures. The posted information does not provide the primary outcome result needed to assess the observed endpoint, and the single-group design would not support a randomized treatment comparison in any case.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly defined endpoint and the absence of a reported endpoint estimate in the registry record. The primary question is specific: the percentage of evaluable participants alive and progression-free at 12 weeks after registration. The record also defines progression using RECIST v1.1. Those definitions make clear what the study intended to measure, but without the numerator, denominator, percentage, and confidence interval, readers cannot assess the observed rate or its precision.

The single-group design also matters. It can describe outcomes in the participants receiving AZD0530, but it does not provide a concurrent randomized comparison. Statistical summaries from a treated group do not, on their own, determine how outcomes would differ under another treatment or no treatment. This distinction is important when interpreting disease outcomes that can be influenced by factors beyond the study intervention.

The stated evaluability rules add another statistical consideration: the primary endpoint denominator depends on eligibility, consent, treatment initiation, and follow-up through the assessment. The count meeting those rules is not reported. Without it, enrollment of 23 cannot be used to reconstruct the endpoint estimate or its uncertainty.

Finally, the record names several secondary outcomes but does not report their results or how multiple outcomes were handled statistically. The planning assumptions described for sample-size illustrations use a two-arm framework, while the registered study design is single group. Keeping planning calculations distinct from the actual design, and from observed evidence, is essential to avoid interpreting an illustration as trial power or as a treatment comparison.

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.

Several limitations specific to this registry record constrain interpretation. The primary endpoint is defined, but its observed percentage and 95% confidence interval are not reported. The number of evaluable participants and the count alive and progression-free at 12 weeks are also not reported. Enrollment of 23 therefore does not reveal the endpoint result or its precision.

The single-group design has no listed concurrent control arm and no randomized allocation. Outcomes among participants receiving AZD0530 cannot be directly compared with outcomes under another treatment using this design. The record lists no masking, so it does not describe a blinded study.

The registry does not report numerical findings for the listed secondary outcomes. It also does not report the statistical analysis plan, sample-size justification, interim analyses, multiplicity handling, or the method used to calculate the primary confidence interval. The number of outcome measures is recorded as four, but detailed results and analysis populations are not reported.

For missing data, the primary endpoint definition excludes participants lost to follow-up before 12 weeks from the evaluable population. The record does not state how many participants were lost, whether other endpoint assessments were unavailable, or how missing information was handled in analyses. For safety, selected event counts and terms are listed, but deaths are not reported in the registry record, and no comparison group is available to contextualize the event figures.

These limitations concern what the registry record reports. They do not establish what may have been documented in a full protocol or publication, neither of which is identified in the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: AZD0530 in Treating Patients With Extensive Stage Small Cell Lung Cancer — NCT00528645.
• Registry record last updated 2017-12-07; status last verified 2017-11.
• Results first posted 2014-02-11.
• 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 II study enrolled 23 participants with extensive-stage small cell lung cancer and evaluated oral AZD0530, also called saracatinib, after four cycles of cytoreductive chemotherapy. Treatment was once daily for up to 2 years unless progression or unacceptable toxicity occurred. The design was single group, with no masking and no concurrent comparator arm listed.

The primary outcome was the percentage of evaluable participants alive and progression-free 12 weeks after registration, using RECIST v1.1 criteria for progression. The registry record does not report the numerical primary result, its confidence interval, or numerical results for the secondary outcomes.

The safety record lists 6 participants with serious adverse events and 22 with other adverse events, each among 23 at risk, as well as selected serious adverse-event terms. The statistical analysis plan, missing-data procedures, and multiplicity approach are not reported in the registry record.