This Is The First Study Using Escalating Doses Of PF-03758309, An Oral Compound, In Patients With Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for This Is The First Study Using Escalating Doses Of PF-03758309, An Oral Compound, In Patients With Advanced Solid Tumors (NCT00932126), a non-randomized phase 1 study. The primary outcome is Number of Participants With Cycle 1 Dose-limiting Toxicities (DLT).

2. Clinical Question

The study was registered as Phase 1 and was described as the first study of PF-03758309 in patients with advanced solid tumors. Its stated aims included assessing safety, blood levels during treatment, and effects on tumor cells. Secondary outcomes covered objective response, time to tumor progression, duration of response, and several measures of plasma concentration and exposure.

Those aims establish the broad questions the study set out to investigate, but they do not establish what the results were. The registry record does not report the primary endpoint count or provide results for the listed secondary outcomes. It also does not describe a control group or a randomized comparison. The clinical question that can be answered from the available record is therefore limited to the study's intended safety and pharmacology assessment and the adverse-event summaries that are posted.

3. Trial Design

This was a Phase 1, open-label, non-randomized, single-group dose-escalation study of PF-03758309 in patients with advanced solid tumors. The registry lists enrollment of 35 participants and identifies Pfizer as the sponsor. The study began in 2009-09, reached primary completion in 2011-12, and is recorded as terminated. The reason for termination is not reported in the registry record.

Open-label means that masking was not used, as reflected in the registry's masking entry. The study was non-randomized, and different doses were administered to different groups. The posted dose groups include PF-03758309 at 1 mg QD, 1 mg BID, 2 mg BID, 10 mg BID, 20 mg BID, 40 mg BID, 50 mg BID, and 60 mg BID. These dose cohorts are not randomized treatment arms, so comparisons between them may reflect differences in who entered each cohort, as well as dose.

The primary endpoint was the number of participants with Cycle 1 dose-limiting toxicities. Its timeframe began at baseline, described as up to 30 days before the first study-drug administration, and continued through 28 days after the last treatment administration, identified as the end of Cycle 1. The primary endpoint's analysis population was the safety analysis set: participants enrolled in the study who received at least 1 dose, including the lead-in dose.

The study also listed outcomes concerning tumor response and progression, response duration, and pharmacokinetic measures. The registry record lists 12 outcome measures, but records no analyses. It does not report a protocol-level statistical analysis plan, details of dose-escalation decisions, or a sample-size justification. Those design details should not be inferred from the posted dose groups or the enrollment figure.

Because there was no randomized comparator and no masking, the design is best understood as an early-phase assessment across dose levels. The dose cohorts can describe what was recorded at each level, but they do not provide the safeguards of a randomized, controlled treatment comparison. The study's termination status also does not, by itself, explain whether the study stopped for safety, operational, scientific, or other reasons.

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.

Only the first 6 of 8 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 participants enrolled in the study that received at least 1 dose of PF-03758309 (including the lead in dose).

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 Cycle 1 Dose-limiting Toxicities (DLT), measured over Baseline (up to 30 days prior to first study drug administration) till 28 days after the last treatment administration (end of Cycle 1 [28 days]).

The primary endpoint counts participants with a dose-limiting toxicity during Cycle 1. A dose-limiting toxicity is a prespecified safety event or treatment limitation that can indicate whether a dose was difficult to tolerate under the study conditions. In an escalating-dose study, this kind of endpoint helps characterize safety at the tested dose levels and can inform decisions about dose evaluation. That is a general explanation of the endpoint's role; the registry record does not state how the study team used the results to make decisions.

The registry definition includes specified blood-related toxicities, other severe toxicities, delayed recovery that prevents restarting treatment, and inability to receive at least 80% of the planned PF-03758309 dose because of study-drug-related toxicity. The listed criteria include Grade 4 neutropenia lasting >7 consecutive days, febrile neutropenia, Grade 3 neutropenia infection, Grade 4 thrombocytopenia, and Grade 3 thrombocytopenia with bleeding. The definition also includes other Grade 3 or higher toxicities not classified as blood or bone marrow events, with stated exceptions for nausea, vomiting, or diarrhea in participants receiving optimal treatment with antiemetics or anti-diarrheals.

The specified timeframe runs from baseline, up to 30 days before the first study-drug administration, until 28 days after the last administration, described as the end of Cycle 1. The record does not report how many participants met the endpoint, the dose-level results for this endpoint, or its uncertainty. The posted adverse-event summaries are not a substitute for the primary endpoint result: serious adverse events and dose-limiting toxicities are distinct measures, and the record does not establish that every serious event met the dose-limiting toxicity definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study design determines what statistical conclusions are available. This was a non-randomized, open-label, single-group dose-escalation study. Participants were treated in different dose groups, but the registry does not describe random assignment or a control group. As a general statistical point, randomized allocation helps balance measured and unmeasured participant characteristics across groups. Without it, differences between dose cohorts can reflect participant mix, timing, or other factors as well as dose. The registry record does not report adjustments for such differences.

What do the adverse-event counts describe?

The posted safety summaries give the number at risk and the number affected for serious adverse events and other adverse events in each dose group. These counts are descriptive. A count of affected participants indicates how many participants in that group were recorded as affected under the registry's summary, but does not give the number of events per participant, event timing, severity beyond the serious-event classification, or attribution to study drug. The record does not report those details. The serious-event term percentages are also listed, but their denominator and calculation method are not reported in the registry record.

For binary outcomes such as whether a participant experienced an event, the observed count is often considered alongside the number of participants assessed. General statistical interpretation also considers uncertainty: estimates from small groups can be imprecise, and a count alone does not show how much the underlying event frequency might vary. No confidence intervals or hypothesis tests for these adverse-event summaries are reported in the registry record. No such estimates should be inferred from the counts.

Why does non-randomized allocation matter?

In general, an unadjusted comparison between groups can be confounded when group membership is related to participant characteristics or study conduct. In a dose-escalation setting, the record says that different doses were given to different groups, but does not give details of cohort entry or adjustment methods. Therefore, observed differences between dose groups are not equivalent to causal treatment effects. The registry itself flags that the arms are not a like-for-like control comparison. The listed dose cohorts are useful for describing recorded observations, not for assuming a controlled contrast.

What does the primary endpoint capture?

The primary endpoint is a participant count for Cycle 1 dose-limiting toxicities. Its definition combines clinical toxicity criteria with treatment-delivery or recovery criteria. This makes it a safety and tolerability measure tied to the study's stated treatment period. General endpoint interpretation depends on applying the definition consistently and having complete follow-up over the specified timeframe. The record gives the definition and timeframe, but does not report the endpoint result, missing observations, or how incomplete follow-up was handled.

What can be said about hypothesis tests and precision?

The registry record lists no analyses. It does not report p-values, confidence intervals, adjusted estimates, or a statistical analysis plan. A confidence interval, in general, expresses the precision of an estimated quantity under specified statistical assumptions; it is not a guarantee that the estimate contains the true value. Without an estimate and its uncertainty, the posted event counts cannot be used to judge statistical precision beyond noting the group sizes recorded. A lack of a reported test is not evidence of no effect, and a descriptive count is not evidence of a statistically established difference.

The record includes a planning illustration based on the observed effect, with 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 stated fraction of the observed effect. For time-to-event outcomes, that illustration is defined in terms of total events, while other illustrations use participants per arm. These are planning assumptions, not the study's documented design rationale. The record does not report the numerical planning results or its own sample-size justification. Such illustrative sample sizes are not observed power and do not establish the study's power to detect an effect.

Why can over-dispersion matter in general?

For count outcomes, some statistical models assume that variability follows a specified distribution. Over-dispersion means the observed variability is greater than that assumption allows; if ignored, standard errors can be too small and uncertainty can appear lower than it is. That is a general consideration for count data, not a claim about this study. The registry record does not report a count model, a dispersion estimate, or an analysis that addresses over-dispersion.

Overall, the available statistical record supports descriptive reading of the reported safety counts and the study's stated endpoints and design. It does not support reconstruction of an inferential analysis, and no unreported model, adjustment, or uncertainty estimate should be assumed.

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-03758309, 1 mg QD", "PF-03758309, 1 mg BID", "PF-03758309, 2 mg BID", "PF-03758309, 10 mg BID", "PF-03758309, 20 mg BID", "PF-03758309, 40 mg BID")
n      <- c(3, 3, 3, 3, 5, 3)
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-03758309, 1 mg QD  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-03758309, 1 mg BID  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-03758309, 2 mg BID  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-03758309, 10 mg BID  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-03758309, 20 mg BID  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  PF-03758309, 40 mg BID  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes, including the primary Cycle 1 dose-limiting toxicity endpoint and secondary measures of objective response, tumor progression, response duration, and plasma concentration or exposure. It reports 12 outcome measures, but no analyses. The record does not describe a multiplicity strategy, such as prioritizing confirmatory tests or adjusting for the number of statistical comparisons. Without reported analyses or a stated plan, it is not possible to determine whether any apparent finding was selected from a larger set of comparisons or how false-positive risk was handled. This is a limitation in what can be interpreted, not evidence that a particular method was or was not used outside the registry record.

Missing-data handling is not reported in the registry record. The record does not state how participants with incomplete follow-up, missing endpoint assessments, or unavailable outcome measurements were treated. It also does not report the number of participants assessed for the primary endpoint. The stated safety analysis set includes enrolled participants who received at least 1 dose, including the lead-in dose, but the record does not give the size of that set or explain how it relates to each posted outcome summary.

The registry describes the primary endpoint population and timeframe, but does not report an analysis population for each secondary outcome, imputation procedures, censoring rules, or sensitivity analyses. Those omissions matter because analysis populations and missing-data methods can affect both the denominator and interpretation of an estimate. The available information does not support assuming that all enrolled participants contributed to every analysis, or that missing observations were handled in a particular way.

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: asthenia (20.0%), abdominal pain (20.0%), disease progression (10.0%), haemoptysis (10.0%).

The serious adverse-event summaries should be read as counts of affected participants within the listed dose groups. The record reports 0 affected among 3 at risk for the 1 mg QD, 1 mg BID, 2 mg BID, 10 mg BID, and 40 mg BID groups; 1 among 5 for 20 mg BID; 1 among 5 for 50 mg BID; and 2 among 10 for 60 mg BID. These are cohort descriptions, not randomized comparisons, and the record does not provide confidence intervals or tests comparing doses.

The registry also lists Asthenia and Abdominal Pain at 20.0% each, and Disease Progression and Haemoptysis at 10.0% each, among the top serious-event terms. The denominator behind these percentages is not reported in the registry record. The percentages should not be treated as event rates within a particular dose group without that information. The record's deaths field is not populated for these groups, so it does not establish a death count.

The separate other-adverse-event summaries record all participants at risk as affected in each dose group. The record does not provide enough detail to infer event counts per participant, severity, timing, or relationship to treatment from those summaries. Serious adverse events should also not be equated with the primary dose-limiting toxicity endpoint: the record does not identify which serious events, if any, met its DLT criteria.

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

The record establishes that PF-03758309 was studied in a Phase 1, open-label, non-randomized dose-escalation study involving patients with advanced solid tumors. It specifies the primary safety endpoint, its DLT criteria, its timeframe, and the safety analysis set definition. It also posts serious and other adverse-event counts for several dose groups, alongside selected serious-event terms and percentages. These are useful descriptive elements of the registry record.

The posted information does not establish the primary endpoint result. It also does not report results for the listed secondary outcomes, including objective response, time to tumor progression, duration of response, or pharmacokinetic measures. There are no reported inferential analyses, confidence intervals, or p-values. The safety counts therefore cannot be used to infer a statistically established difference between doses or to determine the precision of a dose-specific risk estimate.

The non-randomized design limits comparisons across dose groups. Because different doses were given to different groups, the groups may not be exchangeable; the registry does not report methods that would address such differences. The record also does not provide the denominator for the listed serious-event percentages or explain the deaths field, which is not populated. These gaps limit interpretation of the safety summaries.

The study's terminated status is recorded, but the reason for termination is not reported. It cannot be interpreted as proof of a particular safety concern, lack of activity, or other outcome. Likewise, the study's aims and endpoint definitions describe what was intended to be assessed, not the findings. A careful reading separates the recorded design and descriptive adverse-event counts from results that the registry does not report. No treatment-effect conclusion follows from the available information.

14. Why This Trial Matters Statistically

This study illustrates a common early-phase statistical challenge: dose cohorts can generate useful descriptive safety information, while offering limited grounds for formal comparisons. The registry identifies a series of PF-03758309 dose groups and records serious and other adverse-event counts for each. Those summaries can help readers see how the posted data are organized by dose, but the non-randomized allocation means cohort contrasts should not be interpreted like randomized treatment effects.

The primary endpoint also shows why endpoint definitions matter. The registry's DLT definition is not limited to a single clinical event; it includes specified blood-related toxicities, other severe toxicities, delayed recovery, and inability to receive a specified proportion of planned dose because of related toxicity. Its timeframe is tied to Cycle 1. A reader needs that definition to understand what the primary count was meant to capture. However, the registry does not report the count itself, so the endpoint cannot be evaluated from this record.

The difference between a posted safety summary and an analyzed result is important. The counts describe what the registry reports at each dose level. They do not supply uncertainty estimates, adjustments, or a tested contrast. The serious-event term percentages add another interpretive issue because their denominator is not reported. These gaps make transparent reporting of denominators, endpoint results, and analysis methods central to sound statistical interpretation.

Finally, the status entry alone does not explain why the study ended. Separating documented details from possible explanations is especially important when a trial is terminated and its outcome reporting is incomplete. The record supports a clear description of design and selected safety data, but not a conclusion about efficacy, the study's reason for termination, or dose-related causal effects.

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 registry record does not report the primary endpoint result, despite providing a detailed DLT definition and timeframe. It also does not report results for the listed secondary outcomes. This leaves the main safety question and the stated tumor and pharmacokinetic questions unanswered in the posted record.

The study was non-randomized, open-label, and single-group, with different dose levels given to different groups. The record does not describe a randomized comparator, masking, adjusted comparisons, or methods to account for differences among dose cohorts. Therefore, dose-group counts should not be treated as causal comparisons. The record does not report participant characteristics that could help assess cohort comparability.

The adverse-event summaries have limited detail. The denominator behind the serious-event term percentages is not reported, and the deaths field is not populated. The record does not provide event timing, participant-level event histories, causality assessments, or an explanation of the other-adverse-event category. It also does not establish which serious events met the primary DLT definition.

The registry lists 12 outcome measures but no analyses. A statistical analysis plan, multiplicity approach, missing-data methods, and outcome-specific analysis populations are not reported in the registry record. Nor are confidence intervals or p-values reported for the posted counts. The reason for termination and the study's sample-size justification are also not reported. These limitations constrain interpretation without establishing why information is absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: This Is The First Study Using Escalating Doses Of PF-03758309, An Oral Compound, In Patients With Advanced Solid Tumors — NCT00932126.
• Registry record last updated 2015-10-28; status last verified 2015-10.
• Results first posted 2013-03-06.
• 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

NCT00932126 is a Phase 1, open-label, non-randomized, single-group dose-escalation study of oral PF-03758309 in patients with advanced solid tumors. The registry lists enrollment of 35 participants, Pfizer as sponsor, a start date of 2009-09, primary completion in 2011-12, and terminated status. The reason for termination is not reported in the registry record.

The primary endpoint was the number of participants with Cycle 1 dose-limiting toxicities. The record defines the DLT criteria and a safety analysis set, but does not report the primary endpoint result. Secondary outcomes include tumor response and progression measures and pharmacokinetic outcomes; their results are not reported. The registry lists serious and other adverse-event counts by dose group, but no analyses. The dose groups are not randomized comparison arms, and the posted safety information is descriptive rather than a controlled treatment comparison.