Study Of PF-00562271, Including Patients With Pancreatic, Head And Neck, Prostatic Neoplasms: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Of PF-00562271, Including Patients With Pancreatic, Head And Neck, Prostatic Neoplasms (NCT00666926), a non-randomized phase 1 study. The primary outcome is Number of Participants With First Cycle Dose Limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

The registry describes NCT00666926 as a Phase 1, open-label, dose-escalation study of PF-00562271. It was non-randomized and had no masking. The stated objectives were to evaluate safety, pharmacokinetics, and pharmacodynamics in patients with advanced non-hematologic malignancies. The registry lists 99 enrolled participants and gives the study status as completed.

Eligible patients were described as having positive Positron Emission Tomography scans associated with advanced non-hematologic malignancies. The listed conditions include pancreatic, head and neck, and prostatic neoplasms; the brief description also includes other malignancies appropriate for serial biopsy. Screening included FDG-PET and tumor imaging, medical history, physical examination, ECOG performance status, blood draws, and a pregnancy test for female patients of childbearing potential.

PF-00562271 was administered as tablets. Dose groups in the safety record range from PF-00562271 5 mg BID to PF-00562271 225 mg QD, with both BID and QD schedules represented. The brief description says treatment continued until disease progression, unacceptable toxicity, or patient request. The registry classifies the model as crossover, while its title and description emphasize open-label dose escalation. How the crossover classification relates to the dose-escalation conduct is not reported in the registry record. Arm descriptions are blank.

The registry gives a start date of 2005-12 and a primary completion date of 2009-04. It lists 24 outcome measures and three analyses. The record does not describe random assignment, a control group, or a statistical rationale for the enrollment target; those details 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.

Before assignment: Expansion cohort (E1 or E2): participants were to be those enrolled at maximum tolerated dose level. E1: to have advanced disease likely to possess functional aberrations of pathways for tumorigenesis (represent focal adhesion kinase \[FAK\] expression). E2: to have disease characteristics associated with FAK expression and agree to repeat biopsies.

Only the first 6 of 16 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analysis set: All enrolled participants who started treatment.

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 Number of Participants With First Cycle Dose Limiting Toxicities (DLTs), measured over Baseline up to Cycle 1 Day 21 (C1.D21).

The primary endpoint is the number of participants with first-cycle dose-limiting toxicities, assessed from baseline through Cycle 1 Day 21 (C1.D21). It is a count of participants with an event, rather than a continuous measurement or a time-to-event outcome. The population is defined as the safety analysis set: enrolled participants who started treatment.

The registry specifies events considered at least possibly attributable to treatment. These include severe neutropenia or febrile neutropenia, severe thrombocytopenia, severe non-hematologic toxicity despite adequate medical intervention, a confirmed prolonged QTc interval, a confirmed cardiac troponin I result at or above the stated reference-range threshold, and treatment-related toxicity that interfered with completing treatment or resuming the current dose level within the specified period. The criteria are intended to capture toxicities relevant to treatment safety and dose escalation.

General statistical context: an early-phase dose-limiting-toxicity endpoint can help characterize tolerability at studied dose levels and inform decisions about further evaluation. It is not, by itself, a measure of comparative clinical benefit. The registry record does not report the number of participants meeting this primary endpoint, so its observed frequency and uncertainty cannot be described from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context: the methods below explain how to interpret the types of outcomes and planning assumptions described in the registry. They do not imply that a particular analysis was performed unless the registry record says so.

What does a count endpoint represent?

The primary outcome is a participant count: the number of people in the defined safety analysis set who experienced at least one qualifying first-cycle dose-limiting toxicity. A count is different from a measurement such as serum concentration, and it is different from a time-to-event outcome. To interpret a count fully, readers need both the number affected and the relevant population size. Here, the endpoint definition and population are stated, but the primary result and the size of the safety analysis set are not reported in the registry record.

For a binary event outcome, a count can also be expressed relative to the participants assessed. That proportion conveys how common the event was in the observed group, while a confidence interval conveys uncertainty around the estimate. General statistical context: confidence intervals are ranges of values compatible with the data under the stated method; wider intervals indicate less precision. No primary endpoint confidence interval or event proportion is reported in the registry record, so none can be interpreted for this endpoint.

Why does the design matter for comparisons?

Randomization aims to make treatment groups comparable, on average, with respect to measured and unmeasured baseline factors. In a non-randomized study, dose groups may differ for reasons beyond the dose assigned. Consequently, a difference in event counts between dose groups is descriptive unless supported by an appropriate design and analysis. The registry explicitly states that the arms are not a like-for-like control comparison. The record does not report an adjusted dose comparison or a statistical plan for one.

Open-label means masking was absent. General statistical context: when treatment is known, judgments about symptoms, event classification, or further care can potentially be influenced by that knowledge. The record does not describe blinded outcome assessment, and any such arrangement is not reported in the registry record.

How should the safety counts be read?

The serious adverse-event entries give, for each listed dose group, the number at risk and the number affected. For example, the PF-00562271 10 mg BID group lists 4 participants at risk and 1 affected by a serious adverse event; the PF-00562271 35 mg BID group lists 3 at risk and 2 affected; and the PF-00562271 125 mg BID group lists 33 at risk and 12 affected. These are group-specific descriptive counts. They should not be interpreted as evidence of a causal dose effect or compared as if dose assignment had been randomized.

The other-adverse-event entries are a separate set of counts. A serious event and an event in the other category should not be treated as interchangeable categories. The registry does not provide the event definitions or a detailed explanation of how these categories relate to one another. It also does not report the number of events per participant, so counts of participants affected should not be read as counts of all event occurrences.

What do the pharmacokinetic measures describe?

Maximum serum concentration (Cmax) describes the highest measured concentration in the specified sampling period. Tmax describes when the maximum observed concentration occurred. Area under the concentration-time curve summarizes exposure over a specified interval: AUClast runs from time zero to the last quantifiable concentration, while AUCinf extends to an extrapolated infinite time. Serum decay half-life describes the rate of decline in concentration, and apparent oral clearance (CL/F) relates drug administration to observed concentrations while accounting for oral bioavailability in the apparent measure.

These are general interpretations of the named pharmacokinetic measures. Their values can depend on sampling and analysis methods. The registry lists assessments at C0.D1 and C1.D1 for several outcomes and at C1.D14 for some outcomes. Numerical estimates, variability measures, and analysis details are not reported in the registry record, so the measures cannot be used to characterize exposure or compare schedules.

What do the planning assumptions mean?

The sample-size material is described as a planning illustration computed from the observed effect, not the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event tables, the stated quantity is the total number of events using the Schoenfeld approach; for other tables, it is participants per arm.

General statistical context: a planning illustration estimates the amount of information a future comparison might require under its assumptions. It is not the number observed in this study, and it is not observed power. The record does not report the study’s own sample-size justification or a randomized two-arm design. The numerical planning outputs and the effect fractions are not reported in the registry record for this analysis, so no particular planning value can be interpreted.

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("PF-00562271 5 mg BID", "PF-00562271 10 mg BID", "PF-00562271 15 mg BID", "PF-00562271 25 mg BID", "PF-00562271 35 mg BID", "PF-00562271 45 mg BID")
n      <- c(2, 4, 3, 4, 3, 4)
events <- c(0, 0, 0, 0, 0, 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  PF-00562271 5 mg BID  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  PF-00562271 10 mg BID  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  PF-00562271 15 mg BID  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-00562271 25 mg BID  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  PF-00562271 35 mg BID  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-00562271 45 mg BID  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 24 outcome measures and three analyses. It does not report whether these outcomes were assigned a hierarchy, whether one was formally designated as the sole confirmatory test, or whether any multiplicity adjustment was planned or used. The presence of several outcomes does not by itself establish that multiple hypothesis tests were performed. The statistical plan for handling multiple outcomes is not reported in the registry record.

Missing-data methods are also not described. The record does not state how participants with incomplete safety follow-up, missing assessments, or unavailable pharmacokinetic samples were handled. For the primary endpoint, the safety analysis set is defined as enrolled participants who started treatment, but the number in that set and the completeness of endpoint assessment are not reported in the registry record. The enrolled count should therefore not be assumed to equal the endpoint denominator.

The registry names the safety analysis set for the primary endpoint. Other analysis populations, such as the populations used for pharmacokinetic or pharmacodynamic outcomes, are not defined in the information and are not reported in the registry record. The record also does not describe interim analyses, stopping rules, or adjustments for repeated assessment. These design and analysis details cannot be inferred from the listed outcomes or dose groups.

General statistical context: multiplicity can increase the chance of a nominally unusual result when many hypotheses are tested, while missing outcomes can affect both the estimated event frequency and its precision. The impact depends on the analysis plan and on why data are missing. Because the registry does not describe its procedures, it is not possible to assess how these issues were addressed.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastrointestinal haemorrhage (33.3%), diabetes mellitus inadequate control (33.3%), mental status changes (33.3%), renal failure acute (33.3%), urinary retention (33.3%).

The serious adverse-event figures are presented by PF-00562271 dose group as participants at risk and participants affected. For example, the record lists 0 affected among 2 at risk at 5 mg BID, 1 among 4 at 10 mg BID, 2 among 3 at 35 mg BID, and 12 among 33 at 125 mg BID. These entries describe the groups recorded in the registry; they do not establish that dose caused an event or that event frequencies can be compared causally across groups.

The registry separately lists serious-event terms with percentages: gastrointestinal haemorrhage, diabetes mellitus inadequate control, mental status changes, renal failure acute, and urinary retention are each listed at 33.3%; nausea is listed at 25.0%. The denominator and the context of these percentages are not reported in the registry record, so they should not be interpreted as percentages of all enrolled participants or of a particular dose group without further information.

Deaths are not reported in the registry record. The adverse-event figures do not state event relatedness, severity grading beyond the serious-event category, or the duration of follow-up for these events.

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

The study addresses early clinical evaluation of PF-00562271 in patients with advanced non-hematologic malignancies. Its stated focus was safety, pharmacokinetics, and pharmacodynamics, with a primary endpoint that counted participants with specified first-cycle dose-limiting toxicities. The record also contains dose-group adverse-event entries and lists pharmacokinetic outcome measures.

The available information does not report the primary dose-limiting-toxicity result. It therefore cannot establish how many participants met that endpoint, the observed frequency in the safety analysis set, or how precisely that frequency was estimated. The enrollment of 99 does not fill this gap, because the primary analysis population is participants who started treatment and its size is not reported in the registry record.

The serious and other adverse-event entries offer descriptive information for the dose groups. They are not evidence from a randomized comparison, and they do not on their own show that a specific dose caused more or fewer events. The registry’s serious-event term percentages also lack reported denominator context. No efficacy endpoint result is included in the information available for this analysis, and the pharmacokinetic outcomes are listed without their numerical estimates.

Accordingly, the record can be used to understand the study’s design, intended safety endpoint, and the kinds of safety and drug-exposure outcomes assessed. It cannot support a conclusion about comparative benefit, a dose-response relationship, or a treatment effect. These are limitations of the information reported, not a claim that the study did or did not observe particular outcomes.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of an early-phase, non-randomized dose-escalation design in which safety and drug exposure are central aims. The primary endpoint is defined through clinically specified toxicity criteria and a bounded first-cycle assessment period. Defining the event and analysis population matters: an endpoint count is interpretable only alongside the number of participants assessed and a clear account of who was included.

The record also illustrates why design labels and actual comparisons must be read carefully. Multiple dose groups can describe safety experience across exposure levels, but without randomization they do not provide a like-for-like control comparison. The registry explicitly warns against treating these arms as equivalent controls. The crossover model classification alongside the dose-escalation description is another feature whose relationship is not explained in the registry record.

There is a useful distinction between outcome definition and outcome reporting. The registry describes the dose-limiting-toxicity criteria in detail, and it lists pharmacokinetic outcomes and adverse-event counts. Yet the primary endpoint result itself is not reported in the information available for this analysis. A complete definition does not replace the event count, denominator, and uncertainty needed to interpret an observed result.

Finally, the record’s planning assumptions should be separated from the trial’s conduct. A sample-size illustration based on an observed effect and specified assumptions is a planning aid, not observed power and not evidence that the original study was designed around those assumptions. The registry does not report the trial’s sample-size justification or the statistical procedures used to address multiple outcomes and missing data. These distinctions help readers avoid treating design descriptions, planning calculations, and observed results as interchangeable evidence.

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 central limitation for statistical interpretation is that the primary endpoint result is not reported in the registry record. The number of participants meeting the dose-limiting-toxicity definition, the primary endpoint denominator, and an uncertainty estimate are unavailable. Although the record lists 99 enrolled participants, it defines the endpoint population as participants who started treatment and does not give the size of that population.

The design was non-randomized and open label. Dose groups therefore cannot be treated as randomized comparison groups, and the registry explicitly cautions that they are not like-for-like controls. The arm descriptions are blank. The registry classifies the model as crossover, but the relationship between that classification and the dose-escalation description is not reported in the registry record.

The adverse-event data are descriptive and do not include a reported judgment of event relatedness. For the listed serious-event terms, denominator context is not reported in the registry record. Deaths are not reported in the registry record. The listed pharmacokinetic outcomes do not include numerical results in the information available for this analysis.

The record does not report the statistical analysis plan, sample-size justification, handling of missing data, multiplicity procedures, interim analyses, or other analysis populations. It is therefore not possible to assess those features or determine whether analyses followed prespecified procedures. These limitations restrict what can be concluded from the registry information; they should not be filled by assumptions about the study’s conduct.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study Of PF-00562271, Including Patients With Pancreatic, Head And Neck, Prostatic Neoplasms — NCT00666926.
• Registry record last updated 2013-03-21; status last verified 2013-03.
• Results first posted 2012-06-14.
• 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

NCT00666926 is a completed Phase 1, open-label, non-randomized study of PF-00562271 in patients with advanced non-hematologic malignancies. The registry lists 99 enrolled participants, a start date of 2005-12, and a primary completion date of 2009-04. Its stated objectives were safety, pharmacokinetics, and pharmacodynamics.

The primary endpoint counts participants in the safety analysis set with first-cycle dose-limiting toxicities through C1.D21. The endpoint definition is reported, but the primary result is not reported in the registry record. Serious and other adverse-event counts are listed by dose group; pharmacokinetic measures are named without numerical results in the information available for this analysis. The non-randomized dose groups are not a like-for-like control comparison.