A Trial In Patients With Advanced Cancer And Leukemia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial In Patients With Advanced Cancer And Leukemia (NCT00878189), a non-randomized phase 1 study. The primary outcome is Number of Solid Tumor Participants With First-Cycle Dose-Limiting Toxicity (DLT).

2. Clinical Question

3. Trial Design

This was a phase 1 dose-escalation study of PF-03084014 in people with advanced cancer and leukemia. The registry lists 72 participants enrolled and the study status as completed. The recorded start date is 2009-06-25, and the primary completion date is 2013-01-10. Pfizer is listed as the sponsor.

The trial was non-randomized and had no masking. Its stated purpose was to determine the safety of PF-03084014. The registry describes solid tumor participants and participants with T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma; these populations appear in distinct adverse-event groups at some dose levels. Dose groups ranged from PF-03084014 20 mg BID to 330 mg BID for solid tumor participants, with a separate 150 mg BID group for T-ALL/LBL participants. The registry does not describe the assignment procedure or give fuller arm descriptions.

The primary endpoint was the number of solid tumor participants with a first-cycle DLT. The population description restricts DLT evaluation to solid tumor participants enrolled for dose escalation who started treatment and did not have major first-cycle treatment deviations. The registry also lists safety, laboratory, ECG and pharmacokinetic secondary outcomes. It records 50 outcome measures, but no analysis entries. Further details of the statistical analysis plan, dose-escalation rules and sample-size justification are not reported in the registry record.

Because allocation was not randomized and there was no control group, differences among dose groups do not establish comparative treatment effects. Group sizes also vary, and the study includes distinct disease populations. The design is directed toward early-phase safety assessment rather than a randomized estimate of benefit against a comparator.

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 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Solid tumor participants enrolled for dose-escalation who started treatment and who did not have first cycle major treatment deviations (including less than 80% of the planned dose of PF-03084014 in Cycle 1 for reasons other than treatment-related toxicities) were evaluable for DLTs.

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 Solid Tumor Participants With First-Cycle Dose-Limiting Toxicity (DLT), measured over Baseline to the end of Cycle 1 (Week 4).

The primary endpoint counts solid tumor participants who experienced a first-cycle dose-limiting toxicity attributable to PF-03084014. The assessment period runs from baseline to the end of Cycle 1 (Week 4). The endpoint is a count of participants with an event, rather than a measure of tumor response or a time-to-event outcome.

The registry definition includes non-hematologic toxicities at or above Grade 3 despite optimal care; a treatment delay of at least 7 days or inability to deliver at least 80% of the planned dose because of treatment-related toxicities; Grade 4 neutropenia lasting more than 7 days; febrile neutropenia; neutropenic infection; and Grade 3 or higher thrombocytopenia with bleeding.

In dose escalation, a first-cycle DLT endpoint is used to characterize serious or dose-limiting toxicity during a defined early treatment period. It can inform decisions about which dose levels merit further evaluation, but the endpoint alone does not establish a treatment’s overall safety profile. The registry record does not report the observed number of participants meeting this endpoint, so the trial’s primary endpoint result cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary endpoint is a binary participant-level outcome: each person is classified according to whether a qualifying DLT occurred during the defined period. The reported measure is the number of participants with that event. A count is not, by itself, a rate; interpreting the frequency requires the number of participants included in the relevant analysis population as its denominator. The registry provides eligibility criteria for DLT evaluation but does not report the actual evaluable count or the observed primary endpoint count.

General statistical explanation: when a binary outcome is reported as a proportion, the numerator counts participants with the event and the denominator counts participants assessed for that outcome. The resulting estimate describes the observed group. A confidence interval, when reported, communicates uncertainty around an estimate; wider intervals generally indicate less precision. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed from the stated endpoint information.

Why does dose escalation affect interpretation?

The recorded allocation is non-randomized. Dose levels are part of an escalation design, not randomized treatment arms. Participants at different doses may differ in ways that are not described, and disease populations are not identical across all listed groups. A comparison of event counts across these groups can be useful descriptively, but it cannot isolate a dose effect from other differences between participants, treatment periods or groups.

General statistical explanation: random allocation is used in comparative trials to reduce systematic differences between treatment groups. Without randomization, observed differences can reflect both treatment and group composition. Even when a statistical adjustment is possible, it depends on information about relevant participant characteristics and on a prespecified analysis approach. Such details are not reported in the registry record, and no adjusted comparative analysis is listed.

How should serious adverse-event counts be read?

The safety record gives the number at risk and the number affected by serious adverse events and by other adverse events for each listed group. These are participant counts, not event counts: a participant may have more than one event, while the count of affected participants records whether an individual had at least one event in the relevant category. The record does not provide event-level descriptions for every adverse event in these groups, nor does it report the duration or recurrence of events.

General statistical explanation: small groups produce imprecise estimates of event frequency, because a change in the outcome of a single participant can materially affect the observed proportion. The registry’s group counts should therefore be considered descriptive, particularly where only a few participants are at risk. The figures do not form a controlled dose-response analysis.

What do the sample-size assumptions mean?

The stated sample-size assumptions describe planning illustrations based on the observed effect, not the trial’s own design. They use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the illustration is expressed as a total number of events using the Schoenfeld approach; other outcomes are expressed as participants per arm.

These assumptions do not establish that the trial was designed with those features. The study itself is recorded as non-randomized, and no randomized two-arm comparison or trial-specific sample-size justification is reported. The registry record also does not provide the primary endpoint result needed to interpret an illustration based on an observed effect. Planning sample sizes are not observed power, and the registry contains no reported analyses from which to infer power or comparative efficacy.

More generally, statistical methods should be matched to the endpoint, study design and analysis population. For a count of participants with a binary event, analysis can focus on the event frequency and its uncertainty. For multiple endpoints, multiplicity may affect how evidence is interpreted. The particular tests, confidence-interval methods, missing-data handling and multiplicity procedures used in this trial are not reported in the registry record.

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-03084014 20 mg BID in Solid Tumor Participants", "PF-03084014 40 mg BID in Solid Tumor Participants", "PF-03084014 80 mg BID in Solid Tumor Participants", "PF-03084014 100 mg BID in Solid Tumor Participants", "PF-03084014 130 mg BID in Solid Tumor Participants", "PF-03084014 150 mg BID in Solid Tumor Participants")
n      <- c(3, 3, 3, 6, 3, 6)
events <- c(0, 0, 0, 1, 0, 1)
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-03084014 20 mg BID in Solid Tumor Participants  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-03084014 40 mg BID in Solid Tumor Participants  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-03084014 80 mg BID in Solid Tumor Participants  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-03084014 100 mg BID in Solid Tumor Participants  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  PF-03084014 130 mg BID in Solid Tumor Participants  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  PF-03084014 150 mg BID in Solid Tumor Participants  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 50 outcome measures, including the first-cycle DLT endpoint and secondary outcomes covering treatment-emergent adverse events, severity, ECG findings, laboratory abnormalities and pharmacokinetics. It records no analysis entries. The registry record does not report which outcomes were formally analyzed, which were considered primary or secondary in the analysis plan, or how results were selected for reporting.

General statistical explanation: testing or estimating many outcomes creates more opportunities for apparently notable findings to arise by chance. Statistical plans may address this through a prespecified hierarchy or multiplicity adjustment, but the registry record does not report whether either approach was used. The listed secondary outcomes should not be treated as confirmatory findings without their analysis details and results.

The primary endpoint population is described as solid tumor participants enrolled for dose escalation who started treatment and did not have first-cycle major treatment deviations. The registry specifies that participants with less than 80% of the planned dose in Cycle 1 for reasons other than treatment-related toxicities were not evaluable for DLTs. However, the number of participants meeting these criteria and the number excluded are not reported in the registry record.

Missing outcome data, withdrawals, and the handling of incomplete assessments are not reported in the registry record. The record also does not describe whether analyses used an intention-to-treat, treated, evaluable or other analysis population for outcomes beyond the stated DLT population. Consequently, the effect of missing observations or population exclusions on the reported safety information cannot be assessed from this record.

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: gram positive cocci (50.0%), nausea (50.0%), sepsis (50.0%), hypophosphataemia (50.0%), constipation (33.3%).

The safety figures distinguish participants with serious adverse events from participants with other adverse events within each dose group. For example, the serious-event count is 1 of 3 at risk in each of the 20 mg BID and 40 mg BID solid tumor groups, while the 150 mg BID solid tumor group records 8 of 23 at risk. These counts describe participants affected; they do not count the total number of adverse-event episodes.

The other-adverse-event counts are also participant counts. The registry lists 3 of 3 at risk in the 20 mg BID group, 7 of 8 in the 100 mg BID solid tumor group, and 23 of 23 in the 150 mg BID solid tumor group. The counts are reported separately for dose and disease groups, and should not be pooled or compared as if the groups were randomized and otherwise equivalent.

Event terms and percentages are listed for selected serious adverse events, but the registry record does not provide a denominator or selection method alongside those terms. Death counts are not reported in the registry record. The counts do not alone show causality, timing, duration, severity beyond the serious-event classification, or recurrence for individual participants.

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

The record documents a completed, non-randomized phase 1 dose-escalation study of PF-03084014 and identifies a first-cycle DLT endpoint for solid tumor participants. It also records serious and other adverse-event counts across dose groups. These details describe the scope of the safety assessment and the event counts recorded for the listed groups.

The primary endpoint result itself is not reported in the registry record. Without the number of evaluable participants and the number who experienced a DLT, the endpoint’s observed frequency and precision cannot be assessed. The adverse-event counts do not substitute for that missing primary result, because they concern different event categories and populations.

The findings do not establish a causal comparison between doses. The study was not randomized, there was no control group, group sizes vary, and the record includes both solid tumor participants and T-ALL/LBL participants. Differences across groups could reflect differences in participants or other aspects of exposure, and the registry does not report an adjusted comparison.

The record also does not establish comparative efficacy. The outcomes described are chiefly safety, laboratory, ECG and pharmacokinetic measures; no efficacy result is presented in the registry record recorded for this analysis. Nor do the adverse-event counts alone establish that an event was caused by treatment. The registry distinguishes all-causality and treatment-related outcomes in its outcome list, but does not report their results.

Accordingly, the most defensible reading is descriptive: the record identifies the trial design, endpoint definition and adverse-event counts, while leaving key information about the primary endpoint result, analysis methods and missing data unavailable. It cannot support a conclusion about whether treatment should be used.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why early-phase safety data need to be read in the context of their design. Dose escalation generates observations across dose levels, but a non-randomized sequence of groups does not provide the same basis for causal comparison as randomized allocation. The recorded counts can describe what occurred within each group, while remaining insufficient to establish that differences between groups were caused by dose.

The primary endpoint is defined in clinical terms and bounded to Cycle 1 (Week 4), making clear what the DLT count was intended to capture. Its criteria include specified hematologic and non-hematologic events as well as treatment interruption or inability to deliver the planned dose because of treatment-related toxicity. Yet the endpoint count and evaluable denominator are not reported in the registry record. This illustrates that a detailed endpoint definition does not replace the result needed to estimate its frequency.

The trial also includes multiple listed outcomes and more than one disease population. Those features matter when interpreting collections of safety results: denominators and outcome definitions need to be clear, and comparisons require attention to population and analysis methods. The record does not report a statistical plan or multiplicity procedure, so readers cannot determine how the numerous listed measures were prioritized or analyzed.

For biostatisticians and clinical researchers, the central lesson is to separate descriptive safety counts from comparative evidence, and to distinguish a planned endpoint from an observed endpoint result. Registry records can convey important design and outcome definitions, while still leaving uncertainty about analysis populations, precision and the basis for interpretation.

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.

A central limitation is that the registry record does not report the primary endpoint result or the number of participants evaluable for DLTs. The endpoint definition is detailed, but the observed count and its denominator are needed to describe the frequency of first-cycle DLTs. No confidence interval or statistical analysis for this endpoint is reported.

The study has no randomized comparator and no masking. Dose groups therefore cannot be treated as balanced control groups. The listed groups have different numbers at risk, and the record includes both solid tumor and T-ALL/LBL participants. The registry does not describe participant characteristics or provide adjustments that would help account for possible differences across groups.

The adverse-event record is limited to participant counts by group and selected serious-event terms. Death counts are not reported in the registry record. The record does not provide the timing, duration, recurrence, or complete event-level detail needed to interpret the burden of adverse events. It also does not state the denominator or selection method for the displayed serious-event term percentages.

Although 50 outcome measures are listed, the registry records no analyses. Statistical methods, missing-data handling, multiplicity procedures, the analysis populations for most outcomes, and the trial-specific sample-size justification are not reported in the registry record. These omissions constrain assessment of precision, selective reporting and the robustness of any interpretation. The stated planning assumptions do not establish how this trial was actually designed or analyzed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Trial In Patients With Advanced Cancer And Leukemia — NCT00878189.
• Registry record last updated 2019-11-12; status last verified 2019-10.
• Results first posted 2019-11-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00878189 is a completed, non-randomized, unmasked phase 1 dose-escalation study sponsored by Pfizer. It enrolled 72 participants with advanced solid tumors or T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma and evaluated PF-03084014 across dose groups. The registry lists a start date of 2009-06-25 and a primary completion date of 2013-01-10.

The primary endpoint is the number of solid tumor participants with a first-cycle DLT, assessed through the end of Cycle 1 (Week 4). The registry defines the DLT criteria and the population considered evaluable, but does not report the primary endpoint result or the evaluable count. Adverse-event counts are recorded by dose and disease group; they are descriptive and do not represent randomized comparisons.

The registry lists 50 outcome measures and no analysis entries. Statistical methods, missing-data handling and multiplicity procedures are not reported in the registry record.