A Study of PF-04217903 in Patients With Advanced Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of PF-04217903 in Patients With Advanced Cancer (NCT00706355), a na phase 1 study. The primary outcome is Number of Participants With Dose-Limiting Toxicities (DLTs).

2. Clinical Question

This is a safety and dose-characterization question, not a comparison of PF-04217903 with another treatment. The record describes a Phase 1 study in advanced cancer and lists pharmacokinetic outcomes concerning PF-04217903 and its metabolite. It does not report a treatment-effect estimate against a control group, nor does it supply a result for tumor response or another clinical benefit endpoint. Accordingly, the registered question is best read as an early-stage assessment of dose-limiting toxicity alongside drug concentration measures, rather than as a test of comparative effectiveness.

3. Trial Design

The registry identifies this as a Phase 1, single-group study of PF-04217903 in patients with advanced cancer. The study began in 2008-08, and the listed primary completion date is 2011-06. Its current status is terminated. The registry record does not report why the study was terminated, so the status alone does not establish whether termination was related to safety, recruitment, development decisions, or another reason.

The allocation field is listed as not applicable, masking is none, and the study model is single-group. There is no separate control arm in the record. The safety data are organized by dose group: PF-04217903 50 mg, 100 mg, 200 mg, and 150 mg. These groups do not constitute a randomized comparison, and differences between their displayed event counts cannot be interpreted as controlled dose effects. The record describes treatment as oral and daily in its summary, and the primary outcome timeframe refers to each increased treatment dose.

Enrollment is recorded as 16. That is the registry enrollment figure, not necessarily the denominator for every analysis or outcome. For the primary outcome, the defined analysis set is restricted to participants who received the first cycle and did not temporarily or permanently discontinue study medication or miss more than 3 consecutive days of dosing for reasons other than DLT during that cycle. The registry record does not report the number included in that analysis set.

The primary outcome is a participant count for dose-limiting toxicities. The listed secondary outcomes focus on plasma concentrations and pharmacokinetic measures for PF-04217903 and its metabolite PF-04328029, including peak, trough, timing, area-under-the-curve, accumulation, and metabolite-to-parent measures. The record lists 14 outcome measures overall, but does not report their numerical results. It also lists no analyses in the available record. Details of the planned dose-escalation procedure, sample-size justification, randomization, and statistical analysis plan 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.

Period 1: PF-04217903 50 mg

Reasons for not completing this period:

Period 2: PF-04217903 100 mg

Reasons for not completing this period:

Period 3: PF-04217903 200 mg

Reasons for not completing this period:

Period 4: PF-04217903 150 mg

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis population included all enrolled participants who received at least 1 dose of the study 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 Dose-Limiting Toxicities (DLTs), measured over Baseline up to 21 days after the start of each increased treatment dose.

The primary endpoint counts participants with dose-limiting toxicities, rather than measuring the severity of toxicity on a continuous scale. Its timeframe is baseline up to 21 days after the start of each increased treatment dose. The record defines DLT using specified events and circumstances, including selected renal, blood-pressure, blood-count, gastrointestinal, and other non-hematological toxicities, as well as inability to deliver at least 80 percent of the planned dose during Cycle 1 because of non-disease-related adverse events.

In early-phase drug studies, a DLT count can help describe whether treatment-related toxicities occur during a defined period of dose exposure. It is useful for characterizing tolerability in relation to dose and for informing subsequent development decisions. That general purpose does not make the count a complete summary of safety: the endpoint depends on the stated DLT definition, the observation window, dose exposure, and analysis population. Events outside the definition or timeframe may not contribute to this primary count.

The registry record does not report how many participants met the DLT definition. It therefore does not support a numerical estimate of the primary endpoint or a comparison across doses based on DLT counts. The adverse-event summaries are separate safety information and should not be substituted for the missing primary endpoint result. In particular, a count of participants with an adverse event is not automatically a count of participants with a DLT; the criteria are not identical by definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a count: it records how many participants met the registry’s definition of a dose-limiting toxicity. Count outcomes are often summarized with a number of affected participants and a denominator defining who was assessed. The denominator matters because participants may differ in whether they received enough treatment or follow-up to be eligible for assessment. Here, the registry defines a DLT analysis set using first-cycle treatment and continuation criteria, but does not report the size of that set or the DLT count. The enrollment figure alone cannot substitute for either quantity.

What does the DLT definition do?

A protocol definition turns a broad concept such as dose-limiting toxicity into a prespecified classification rule. The record includes particular grades and types of toxicity, with exceptions for some events, and also includes an inability to deliver at least 80 percent of the planned dose during Cycle 1 due to non-disease-related adverse events. This makes the endpoint specific to the study’s own definition rather than a universal measure that can be assumed identical across trials. General statistical interpretation depends on keeping the definition, timeframe, and analysis population together: a count is meaningful only in relation to the rules used to decide who qualifies as an event and who qualifies for assessment.

Why does the analysis population matter?

The registry’s DLT analysis set includes participants who received the first cycle of study medication and did not temporarily or permanently discontinue or miss more than 3 consecutive days of PF-04217903 dosing for reasons other than DLTs within that cycle. These eligibility rules can affect the interpretation of a participant count. For example, a count restricted to a defined safety population is not automatically the same as a count among everyone enrolled. The record does not give the number in the DLT analysis set, how participants excluded from it were handled in other analyses, or how missing observations were treated.

In general, a confidence interval expresses uncertainty around an estimate under specified statistical assumptions. For a count or event proportion, it can help convey how compatible the data are with a range of underlying event frequencies. A narrow interval usually indicates greater precision than a wide interval, while small samples commonly leave substantial uncertainty. No confidence interval for the primary endpoint is reported in the registry record, and none can be reconstructed without the corresponding result and analysis details. A p-value would address a specified statistical hypothesis under an analysis plan; no primary endpoint p-value or testing plan is reported.

What can the dose-group summaries establish?

The displayed safety information is grouped by dose, but the study is single-group and has no randomized control arm. In general, dose-group counts can describe what was observed in each group, but a comparison between groups is vulnerable to differences in who entered each group, how much treatment they received, and how their observation periods aligned. Random assignment and an appropriate comparison design can help support causal contrasts; they are not recorded. Consequently, the dose-stratified counts should be presented descriptively, without treating them as controlled estimates of dose effects.

The registry lists serious adverse-event counts and counts for other adverse events. Those categories describe reported safety events, while the primary DLT endpoint applies its own criteria and observation period. A participant can have an adverse event that does not meet the DLT definition, and the registry record does not state that the serious adverse-event counts equal the DLT counts. Keeping those measures distinct avoids interpreting a broad adverse-event summary as if it were the primary endpoint.

How should the pharmacokinetic outcomes be understood?

The listed secondary outcomes describe drug and metabolite concentrations over time. Cmax is the maximum observed plasma concentration, Cmin is the minimum observed plasma trough concentration, Tmax is the time to the maximum observed concentration, and Ctrough is the pre-dose plasma concentration. AUC measures summarize concentration over a defined time interval; the record lists AUC from zero to the last measured concentration and AUC from time zero to the end of the dosing interval. The accumulation ratio describes accumulation across dosing, and the metabolite-to-parent AUC ratio relates exposure to PF-04328029 and PF-04217903.

These are general descriptions of pharmacokinetic concepts. Such measures characterize concentration and exposure, not clinical benefit by themselves. Their interpretation depends on the reported values, sampling schedule, and analysis methods. The registry record names these outcomes but does not report their results or the analysis details needed to assess them.

What do sample-size illustrations mean?

Any sample-size illustrations associated with the posted results are planning calculations, not observed power. The described assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. Those assumptions describe a hypothetical planning exercise, not this trial’s design. This study is recorded as single-group and does not have a randomized two-arm comparison. A planning calculation based on an observed effect does not show that the trial had a particular probability of detecting an effect, nor does it repair the absence of a reported primary result. The registry record does not report its own sample-size justification.

No recalculated primary outcome is available because the registry record does not report the primary endpoint count. The record also does not report an analysis plan, interim analyses, or a method for handling multiplicity. These absences limit how far statistical interpretation can go: the available description supports an account of the intended measurement and a cautious reading of descriptive safety counts, but not an inferential conclusion about DLT frequency or treatment effects.

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-04217903 50 mg", "PF-04217903 100 mg", "PF-04217903 200 mg", "PF-04217903 150 mg")
n      <- c(3, 7, 2, 4)
events <- c(0, 0, 2, 2)
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-04217903 50 mg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-04217903 100 mg  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9
ARM  PF-04217903 200 mg  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2
ARM  PF-04217903 150 mg  4  2  50.0  6.8  93.2  15.0  85.0  14.7  85.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 14 outcome measures, including a primary DLT count and secondary pharmacokinetic outcomes for PF-04217903 and its metabolite. Testing or estimating several outcomes can raise multiplicity concerns: when many hypotheses are examined, the chance of finding at least one apparently notable result can increase if no adjustment or hierarchy is planned. That is a general statistical issue, not evidence that a particular adjustment was or was not used in this study. The multiplicity plan is not reported in the registry record.

The record does not report an analysis plan, interim analyses, or how any interim findings would affect statistical interpretation. It also does not report a missing-data method for the primary endpoint or the pharmacokinetic outcomes. Missingness can matter when participants do not complete the relevant observation period or when measurements are unavailable; analyses may be affected depending on why data are missing and how they are handled. No assumptions about those reasons or methods can be made from the registry information.

The primary endpoint has a defined analysis population based on first-cycle receipt and continued dosing, with specified exceptions. This population definition is important, but the registry record does not report its size or explain how participants outside it were included in other summaries. The enrollment figure should therefore not be treated as the denominator for every outcome. The record lists no analyses, and no primary endpoint count or uncertainty estimate is reported. These omissions prevent assessment of the actual missing-data handling, multiplicity control, and analysis-population implementation.

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: renal failure acute (50.0%), abdominal pain (25.0%), alanine aminotransferase increased (25.0%), aspartate aminotransferase increased (25.0%), dehydration (25.0%).

The serious adverse-event summaries are organized by PF-04217903 dose. The record reports 0 of 3 participants affected at 50 mg, 3 of 7 at 100 mg, 1 of 2 at 200 mg, and 2 of 4 at 150 mg. For other adverse events, it reports 3 of 3, 7 of 7, 2 of 2, and 4 of 4, respectively. These are descriptive counts, not results from a randomized comparison. The groups are not like-for-like controls, and the small denominators mean that a change in one participant’s status would materially alter the displayed count.

The listed serious-event terms include renal failure acute (50.0%) and abdominal pain, alanine aminotransferase increased, aspartate aminotransferase increased, dehydration, and hypercalcaemia (25.0% each). The registry record does not provide denominator context for these term percentages, so they should not be converted into risks or compared across dose groups. It also does not report deaths for the dose groups. These summaries are separate from the primary DLT count, which is not reported, and the record does not establish that every serious adverse event met the DLT definition.

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

The registry record supports a limited but clear description of the study: it was a Phase 1, single-group investigation of PF-04217903 in patients with advanced cancer, with a primary endpoint counting participants with dose-limiting toxicities and secondary outcomes focused largely on drug and metabolite exposure. The record also gives descriptive adverse-event counts by dose. Those details identify the study’s purpose and some of the information collected.

The posted record does not report the primary DLT count, the size of the DLT analysis set, or the numerical results for the listed pharmacokinetic outcomes. It therefore does not establish the observed frequency of DLTs in the defined analysis population, and it does not permit an assessment of the precision of that frequency. The adverse-event summaries cannot stand in for the primary endpoint because the definitions and reporting categories are not stated to be equivalent.

The design does not include a randomized comparator. Accordingly, the safety counts should not be interpreted as evidence that one dose caused more events than another, or as a comparison with standard care or another treatment. No comparative clinical benefit result is reported in the record. While the study summary describes a proposed mechanism and the official title refers to safety, pharmacokinetic, and pharmacodynamic assessment, a biological rationale is not itself evidence of a clinical outcome. The registered outcome results are needed to answer what was observed.

The status is terminated, but the record does not report the reason. That status does not, by itself, indicate a particular safety finding or explain why the study ended. Likewise, the absence of posted results in the record should not be interpreted as a result showing that an endpoint did not occur. It means that the relevant result is not reported in the registry record.

In short, the available information describes the design, endpoint definitions, and selected safety summaries, but it does not support a conclusion about the primary DLT outcome, pharmacokinetic findings, or efficacy. Any interpretation should remain descriptive and tied to the reported populations and event definitions.

14. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint is only one part of statistical reporting. The registry specifies a primary outcome, a DLT definition, a timeframe, and a restricted analysis population. Those details are necessary for understanding what a reported count would mean. Without the number of participants meeting the endpoint and the denominator analyzed, however, readers cannot estimate the observed frequency or its precision.

The study also shows why dose-group summaries in an early-phase single-group trial need careful framing. Displaying counts across doses can be useful descriptively, but it does not create a randomized comparison. The groups may differ in exposure and in other ways, and the denominators are small. Reading the groups as treatment arms in a controlled comparison would overstate what the design can answer.

The separation between DLTs and adverse events is another statistical point of practical importance. A broad safety summary and a protocol-defined primary endpoint answer related but different questions. Maintaining that distinction prevents event counts from being treated as interchangeable and clarifies what further reporting would be needed to interpret the primary safety question.

Finally, the record names multiple pharmacokinetic outcomes alongside the DLT endpoint, but does not report their numerical results or the analysis plan. That makes transparent outcome reporting, analysis-population accounting, and clear descriptions of missing-data and multiplicity methods especially important. These considerations do not imply a particular finding. They identify what readers need in order to judge the reliability and scope of any findings that may be reported.

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 is that the registry record does not report the primary endpoint result. It gives the DLT definition and assessment window, but not the count of participants with DLTs or the number included in the DLT analysis set. The enrollment figure of 16 cannot be assumed to be the denominator for that endpoint because the analysis set has additional eligibility conditions.

The study is recorded as single-group, with no masking and no allocation to a comparator. The dose-specific safety counts are therefore descriptive rather than randomized comparisons. Small group denominators also make those counts imprecise as descriptions of event frequency. No uncertainty intervals are reported for the safety summaries, and there is no posted analysis from which to assess adjusted comparisons.

The record lists secondary pharmacokinetic outcomes but does not report their values. Although the study title refers to pharmacodynamic assessment, the listed outcomes available in the record do not provide a numerical pharmacodynamic result. A tumor-response result is not reported in the registry record. The safety summaries cannot answer either of those questions.

Additional design and analysis details are absent: the registry record does not report a sample-size justification, statistical analysis plan, interim analyses, multiplicity approach, or missing-data methods. It also does not report the reason for termination. These omissions restrict interpretation of both the planned methods and the findings; they should not be filled with assumptions about why the study ended or how unreported results would have been analyzed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of PF-04217903 in Patients With Advanced Cancer — NCT00706355.
• Registry record last updated 2012-06-25; status last verified 2012-06.
• Results first posted 2012-05-31.
• 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 is a Phase 1, single-group study of PF-04217903 in patients with advanced cancer. The registry lists enrollment of 16, no masking, and a terminated status. The primary endpoint is the number of participants with DLTs from baseline up to 21 days after the start of each increased treatment dose, using a specified DLT analysis population. The primary outcome result is not reported in the registry record.

Safety summaries are listed for PF-04217903 50 mg, 100 mg, 200 mg, and 150 mg; these are descriptive dose-group data, not a randomized comparison. Secondary outcomes include pharmacokinetic measures for PF-04217903 and metabolite PF-04328029. Their results, the primary analysis population size, the statistical analysis plan, and the reason for termination are not reported in the registry record.