This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for PF-00477736 Is Being Studied In Advanced Solid Tumors In Combination With Chemotherapy With Gemcitabine (NCT00437203), a non-randomized phase 1 study. The primary outcome is Maximum Tolerated Dose (MTD) of PF-00477736 When Administered in Combination With Gemcitabine.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00437203 |
| Phase | Phase 1 |
| Condition | Neoplasms |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 43 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced solid tumors or other advanced solid malignancies. The registry record reports an enrollment of 43. It defines the full analysis set as enrolled participants who received at least 1 dose of study medication; the number meeting that definition is not reported in the registry record.
Intervention
PF-00477736 administered in combination with gemcitabine. The listed cohorts used differing PF-00477736 doses and administration durations, and some used different gemcitabine doses. The registry record does not provide a complete treatment schedule or describe how dose levels were selected.
Comparator
There was no separate control group: the study is recorded as non-randomized and single-group. Cohorts with different regimens are not a randomized, like-for-like control comparison, so differences between their results would not by themselves establish a treatment effect.
Primary question
What is the maximum tolerated dose of PF-00477736 when administered with gemcitabine, measured in mg through Day 21 of Cycle 1? The registry describes a safety objective and a dose-finding question. It does not report the numerical maximum tolerated dose or enough detail to determine how that endpoint was defined.
3. Trial Design
This was a Phase I study of PF-00477736 with gemcitabine in patients with advanced solid malignancies. The registry describes PF-00477736 as being studied in humans for the first time. Its brief summary states that the study aimed to assess overall safety and determine the maximum dose of PF-00477736 that could be given safely with gemcitabine. The study is listed as non-randomized, unmasked, and single-group, with an enrollment of 43.
The intervention descriptions identify PF-00477736 and gemcitabine. The adverse-event record lists cohorts with different doses and administration durations of PF-00477736, as well as gemcitabine doses of 750 mg/m^2 or 1000 mg/m^2. These cohorts are not described as randomized groups or as a concurrent control. The arm description field is empty, and the registry record does not report the allocation process beyond identifying the study as non-randomized.
The listed timeframe for the primary endpoint is up to Day 21 of Cycle 1. The full analysis set includes enrolled participants who received at least 1 dose of study medication. Whether all enrolled participants received a dose, and therefore how many were in that analysis set, is not reported in the registry record.
The study status is terminated. Its start is recorded as 2006-12 and its primary completion as 2011-04. The reason for termination and any details about stopping the study are not reported in the registry record. The record does not describe a comparator arm, masking, or a randomized treatment assignment; none should be inferred from the presence of multiple cohorts.
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 10 groups are shown.
Overall Study
| Stage | PF-00477736 50 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 1) | PF-00477736 65 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 2) | PF-00477736 80 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 3) | PF-00477736 80 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 4) | PF-00477736 120 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 5) | PF-00477736 180 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 6) |
|---|---|---|---|---|---|---|
| STARTED | 6 | 8 | 3 | 3 | 3 | 3 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 8 | 3 | 3 | 3 | 3 |
Reasons for not completing this period:
| Reason | PF-00477736 50 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 1) | PF-00477736 65 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 2) | PF-00477736 80 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 3) | PF-00477736 80 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 4) | PF-00477736 120 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 5) | PF-00477736 180 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 6) |
|---|---|---|---|---|---|---|
| Death | 0 | 0 | 1 | 0 | 0 | 0 |
| Adverse Event | 1 | 1 | 0 | 0 | 0 | 0 |
| Study terminated by sponsor | 0 | 0 | 0 | 0 | 0 | 0 |
| Objective progression or relapse | 5 | 6 | 2 | 3 | 3 | 3 |
| Other | 0 | 1 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) included all enrolled participants who received at least 1 dose of study medication.
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.
Only the first 6 of 11 groups are shown.
| Characteristic | Unit | PF-00477736 50 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 1) | PF-00477736 65 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 2) | PF-00477736 80 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 3) | PF-00477736 80 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 4) | PF-00477736 120 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 5) | PF-00477736 180 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 6) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 6 | 8 | 3 | 3 | 3 | 3 | |
| Age Continuous | years | 55.2 (SD 18.3) | 62.3 (SD 6.8) | 55.0 (SD 5.2) | 45.0 (SD 3.6) | 55.0 (SD 11.5) | 44.3 (SD 12.1) |
| Sex: Female, Male: Female | Participants | 2 | 2 | 3 | 2 | 1 | 1 |
| Sex: Female, Male: Male | Participants | 4 | 6 | 0 | 1 | 2 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of PF-00477736 When Administered in Combination With Gemcitabine, measured over Up to Day 21 Cycle 1.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the maximum tolerated dose of PF-00477736 when administered with gemcitabine, expressed in mg. Its timeframe is up to Day 21 of Cycle 1. The full analysis set is defined as all enrolled participants who received at least 1 dose of study medication.
A maximum tolerated dose is a dose-finding endpoint: it is intended to identify a dose level that meets a protocol-defined tolerability rule. In general, such an endpoint is useful in early-phase studies because it focuses on dose and safety rather than estimating comparative efficacy. The specific rule used to define the maximum tolerated dose in this study, including any toxicity criteria or decision procedure, is not reported in the registry record. The endpoint description also does not state how participants were assigned among dose cohorts or how evaluable participants were determined.
The registry lists the endpoint but does not report its numerical value or an analysis. Consequently, the record does not establish which dose, if any, was identified as the maximum tolerated dose. The presence of dose levels in the adverse-event cohort descriptions is not a substitute for the primary endpoint result: adverse-event counts alone do not reveal the endpoint's prespecified decision rule or its final determination.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the registry record names a primary endpoint but gives no numerical maximum tolerated dose and no analysis for it. The objective is therefore identifiable, but the posted information does not show the study's answer to its main dose-finding question. A primary endpoint title or an intended timeframe is not itself an observed result.
The record does provide adverse-event counts by cohort. For serious adverse events, the listed affected counts include 1 of 6 participants in Cohort 1, 3 of 8 in Cohort 2, 2 of 3 in Cohort 3, and 0 of 3 in Cohort 5. The corresponding at-risk counts and affected counts are shown for the other listed cohorts as well. These are small cohort counts, and the groups differ in dose or administration duration; some also differ in gemcitabine dose. Since allocation was non-randomized and there is no separate control group, contrasts among the cohorts should not be read as controlled estimates of a dose effect.
The record lists other adverse events separately from serious adverse events. It gives affected counts for both categories by cohort, but does not supply the event definitions, observation windows, or a fuller account of how events were collected. The serious-event terms listed include Injection site reaction, Non-cardiac chest pain, Pyrexia, Sudden death, Neoplasm malignant, and Myoclonus, each with a reported value of 33.3%. The record does not specify the denominator or further context for those term-level percentages in the information available, so they should not be treated as participant-level risks for a particular cohort.
The study is marked terminated, but no reason is reported. The registry also lists objective response and pharmacokinetic outcomes, including plasma concentration and urine concentration measures; numerical results for these outcomes are not reported in the registry record. Taken together, the posted information supports a description of the study design and selected safety counts, not a conclusion about the primary endpoint, comparative efficacy, or the reason for termination.
9. Statistical Methods Explained
For an early-phase dose-finding study, the main statistical task is usually to use observed safety information to guide decisions about dose levels. General methods may use protocol-defined toxicity criteria, rules for how many participants are assessed at each dose, and instructions for escalation or de-escalation. Those details determine how the data translate into a maximum tolerated dose. The registry record does not report the criteria or decision procedure used in this study, so it is not possible to reconstruct that method from the cohort list alone.
What does the primary endpoint represent?
The primary endpoint is a dose, measured in mg, rather than a treatment-effect contrast between two randomized groups. Its timeframe is up to Day 21 of Cycle 1. In general, a dose-finding endpoint condenses observed tolerability into a decision about a dose level under the study's protocol. That decision depends on what counts as a dose-limiting event, which participants are evaluable, and how the protocol handles incomplete observation. These definitions are not reported in the registry record. The record also does not report an estimate, uncertainty interval, or analysis for the maximum tolerated dose.
Why do the cohort counts need cautious interpretation?
The listed cohorts contain different combinations of PF-00477736 dose and administration duration, and the gemcitabine dose differs in some cohorts. This is not a randomized comparison. In general, randomization helps balance measured and unmeasured factors between groups, while non-random allocation can leave those factors unevenly distributed. Cohort differences may also reflect changes to the regimen over the course of a dose-finding study. The record does not describe the allocation rules or timing of those decisions. Therefore, comparisons of observed counts across cohorts are descriptive, not unbiased causal estimates of what changing one dose would do.
Small group counts also make observed proportions unstable: a change in the outcome of a single participant can have a marked influence on a proportion when the denominator is small. General confidence intervals describe the range of values compatible with data and a statistical model; they convey precision, not certainty. No confidence interval for the primary endpoint is reported. The adverse-event record supplies counts, but no uncertainty intervals or model-based comparisons.
What can be said about significance testing?
The registry reports no analyses. Accordingly, it supplies no test statistic, p-value, or inferential comparison for the primary endpoint. The listed secondary outcomes include objective response and several pharmacokinetic measures, but their titles alone do not establish that an analysis was conducted or what it found. Statistical significance, if it had been reported, would address compatibility with a specified statistical null under model assumptions; it would not establish clinical importance or remove limitations from a non-randomized design.
The sample-size planning assumptions describe a general illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a fraction of the observed effect. Such an illustration is not a description of the trial's actual design: this study is listed as single-group and non-randomized, and no randomized two-arm comparison is recorded. The numerical planning outputs and the observed effect used for them are not reported in the registry record. Planning illustrations are not observed power and should not be interpreted as a retrospective measure of the study's ability to detect an effect.
What does over-dispersion mean in general?
For count outcomes, a statistical model may assume a particular amount of variability. Over-dispersion means the observed variability exceeds that model's assumption. If it is ignored, standard errors can be too small and confidence intervals too narrow, making evidence appear more precise than it is. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report a count model, a dispersion estimate, or an analysis plan, so there is no basis to say that over-dispersion was assessed in this study.
Similarly, general methods for time-to-event data account for how long each participant is observed and whether an event has occurred by the end of observation. No time-to-event primary endpoint or analysis is reported. The listed plasma and urine concentration outcomes are pharmacokinetic measures; interpreting them would require the associated measurement schedule, analysis definitions, and numerical results, which are not reported in the registry record. The outcome names alone do not provide estimates or their precision.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary maximum-tolerated-dose endpoint and 11 outcome measures in total. Secondary outcomes include objective response and several pharmacokinetic measures, such as maximum and minimum observed plasma concentrations, times to maximum concentration, area-under-the-curve measures, and PF-00477736 concentration in urine. Their inclusion indicates that multiple outcomes were listed, but the record does not report numerical results or analyses for them.
Multiplicity is the general issue that arises when several outcomes, timepoints, subgroups, or statistical tests are examined. If many tests are conducted, the chance of at least one apparently unusual result can increase. A statistical plan may specify a primary outcome, testing sequence, or adjustment method to address that issue. The registry does not report such a plan, any multiplicity adjustment, or an analysis hierarchy beyond identifying the primary endpoint. No conclusion should be drawn that an adjustment was or was not used outside what is recorded.
Missing-data methods and the amount of missing outcome data are also not reported in the registry record. The full analysis set is defined as enrolled participants who received at least 1 dose of study medication, but the number who met that definition is not given. The record does not describe participants who did not receive a dose, incomplete assessments, withdrawals, or how missing observations were handled. The enrollment of 43 should not be assumed to equal the size of the full analysis set.
There are 0 analyses recorded. Thus, there are no posted estimates from which to assess precision, missing-data sensitivity, multiplicity, or consistency across outcomes. The registry record also does not report an analysis population for each secondary outcome or explain whether all listed outcomes were assessed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| PF-00477736 50 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 1) | 1 | 6 | 16.7% |
| PF-00477736 65 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 2) | 3 | 8 | 37.5% |
| PF-00477736 80 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 3) | 2 | 3 | 66.7% |
| PF-00477736 80 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 4) | 1 | 3 | 33.3% |
| PF-00477736 120 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 5) | 0 | 3 | 0.0% |
| PF-00477736 180 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 6) | 2 | 3 | 66.7% |
| PF-00477736 270 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 7) | 4 | 7 | 57.1% |
| PF-00477736 340 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 8) | 2 | 3 | 66.7% |
| PF-00477736 180 mg 24 Hrs + Gemcitabine 1000 mg/m^2 (Cohort 9) | 0 | 3 | 0.0% |
| PF-00477736 225 mg 24 Hrs + Gemcitabine 1000 mg/m^2 (cohort10) | 3 | 4 | 75.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| PF-00477736 50 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 1) | 6 of 6 |
| PF-00477736 65 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 2) | 8 of 8 |
| PF-00477736 80 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 3) | 3 of 3 |
| PF-00477736 80 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 4) | 3 of 3 |
| PF-00477736 120 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 5) | 3 of 3 |
| PF-00477736 180 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 6) | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | PF-00477736 50 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 1) | PF-00477736 65 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 2) | PF-00477736 80 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 3) | PF-00477736 80 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 4) | PF-00477736 120 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 5) | PF-00477736 180 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 6) |
|---|---|---|---|---|---|---|---|
| Pyrexia | General disorders | 0 of 6 | 2 of 8 | 1 of 3 | 1 of 3 | 0 of 3 | 0 of 3 |
| Coronary artery disease | Cardiac disorders | 1 of 6 | 0 of 8 | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Injection site reaction | General disorders | 0 of 6 | 0 of 8 | 1 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Non-cardiac chest pain | General disorders | 0 of 6 | 0 of 8 | 1 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Cellulitis | Infections and infestations | 0 of 6 | 1 of 8 | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Urinary tract infection | Infections and infestations | 0 of 6 | 1 of 8 | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Blood creatinine increased | Investigations | 0 of 6 | 1 of 8 | 0 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Myoclonus | Nervous system disorders | 0 of 6 | 0 of 8 | 1 of 3 | 0 of 3 | 0 of 3 | 0 of 3 |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | 0 of 6 | 0 of 8 | 0 of 3 | 0 of 3 | 0 of 3 | 1 of 3 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 0 of 6 | 0 of 8 | 0 of 3 | 0 of 3 | 0 of 3 | 1 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | PF-00477736 50 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 1) | PF-00477736 65 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 2) | PF-00477736 80 mg 3 Hrs + Gemcitabine 750 mg/m^2 (Cohort 3) | PF-00477736 80 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 4) | PF-00477736 120 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 5) | PF-00477736 180 mg 24 Hrs + Gemcitabine 750 mg/m^2 (Cohort 6) |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 5 of 6 | 7 of 8 | 3 of 3 | 2 of 3 | 1 of 3 | 1 of 3 |
| Nausea | Gastrointestinal disorders | 2 of 6 | 4 of 8 | 2 of 3 | 1 of 3 | 2 of 3 | 2 of 3 |
| Constipation | Gastrointestinal disorders | 2 of 6 | 5 of 8 | 2 of 3 | 1 of 3 | 1 of 3 | 1 of 3 |
| Neutropenia | Blood and lymphatic system disorders | 3 of 6 | 3 of 8 | 0 of 3 | 3 of 3 | 1 of 3 | 1 of 3 |
| Vomiting | Gastrointestinal disorders | 3 of 6 | 1 of 8 | 2 of 3 | 0 of 3 | 1 of 3 | 2 of 3 |
| Oedema peripheral | General disorders | 2 of 6 | 4 of 8 | 2 of 3 | 0 of 3 | 0 of 3 | 1 of 3 |
| Diarrhoea | Gastrointestinal disorders | 2 of 6 | 1 of 8 | 1 of 3 | 1 of 3 | 1 of 3 | 1 of 3 |
| Pyrexia | General disorders | 0 of 6 | 1 of 8 | 3 of 3 | 0 of 3 | 1 of 3 | 1 of 3 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 2 of 6 | 2 of 8 | 0 of 3 | 0 of 3 | 1 of 3 | 1 of 3 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 6 | 2 of 8 | 0 of 3 | 1 of 3 | 1 of 3 | 0 of 3 |
Serious events with the highest arm-level rate: injection site reaction (33.3%), non-cardiac chest pain (33.3%), pyrexia (33.3%), sudden death (33.3%), neoplasm malignant (33.3%).
The safety figures are counts within the listed cohorts, not comparative treatment effects. For each cohort, the record gives the number at risk and the number affected by serious adverse events, and separately gives the number at risk and affected by other adverse events. For example, Cohort 2 lists 3 of 8 participants affected by serious adverse events and 8 of 8 affected by other adverse events. Cohort 5 lists 0 of 3 affected by serious adverse events and 3 of 3 affected by other adverse events. These figures describe the registry entries; they do not establish that the regimens differ in safety.
The serious-event term list includes Injection site reaction, Non-cardiac chest pain, Pyrexia, Sudden death, Neoplasm malignant, and Myoclonus, each reported as 33.3%. The registry record does not give the denominator or enough context to interpret those percentages as the proportion of all participants affected. The death field is not reported in the registry record. The listed term “Sudden death” should not be equated with a separate death count or used to infer the circumstances of an event.
The cohort sizes are small, and the regimens vary across cohorts. Counts therefore need to be read as descriptive safety information, without treating numerical differences as evidence of a causal dose relationship.
12. What the Result Does, and Does Not, Mean
The record establishes that PF-00477736 was studied with gemcitabine in a Phase I, non-randomized, single-group study of patients with advanced solid malignancies. It records the aim of determining a maximum tolerated dose, gives the endpoint timeframe, defines the full analysis set, and lists safety counts by cohort. It also lists secondary response and pharmacokinetic outcomes.
It does not report the numerical maximum tolerated dose, a primary-endpoint analysis, or numerical results for the listed secondary outcomes. Consequently, the posted results do not answer the central dose-finding question. The study's stated objective is not evidence that a particular dose was identified, and the absence of a numerical result in the registry record should not be interpreted as a particular outcome.
The adverse-event counts describe what was recorded in the listed cohorts. They cannot establish that one regimen caused more or fewer events than another. The study was not randomized, had no separate control group, and used cohorts with differing regimens. Differences may reflect factors other than the dose being considered. The available counts also do not provide a complete safety profile: event definitions, observation details, and the interpretation of term-level percentages are not reported.
The registry lists the study as terminated, but does not state why it was terminated. That status alone does not establish that safety concerns, lack of activity, an administrative decision, or any other particular reason led to termination. No such explanation should be inferred from the record.
These limitations matter especially because the study is described as the first study of PF-00477736 in humans. Early-phase evidence is generally intended to characterize dose and safety in the studied setting; it is not, by itself, a controlled estimate of comparative benefit. The record supports a limited description of design and selected adverse-event counts, but not a conclusion about treatment efficacy, overall safety, or a recommended dose.
13. Why This Trial Matters Statistically
This study illustrates how a clear research objective and an interpretable result are different things. The registry identifies maximum tolerated dose as the primary endpoint and describes its timeframe, but does not post the endpoint value or analysis. For statistical interpretation, the endpoint label alone is insufficient: readers need the observed result, the decision rule, and enough information about the analysis population to understand how the result was obtained.
It also shows why early-phase cohort counts should not be treated like randomized comparisons. The study is non-randomized and single-group, and the listed cohorts vary in regimen. The adverse-event counts can describe what was recorded in those groups, but they cannot isolate the effect of changing one component of treatment. This distinction is important whenever dose levels are discussed across cohorts.
The record includes multiple outcomes, from objective response to pharmacokinetic measurements, but reports 0 analyses. This makes the difference between an outcome being named and its evidence being available especially visible. Without estimates and measures of precision, readers cannot assess the magnitude or uncertainty of those outcomes, or evaluate how multiple outcomes were handled.
Finally, the terminated status has no accompanying explanation in the registry record. Statistical interpretation should remain bounded by the documented details rather than filling that gap with a plausible narrative. Together, these features make the record useful for understanding the intended question and the limits of what can be concluded from the posted results.
14. 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 has several limitations specific to interpreting this study. It does not report a numerical primary-endpoint result, despite identifying maximum tolerated dose as the primary outcome. It also does not report the protocol criteria for that endpoint, such as how tolerability was defined or how a dose decision was made. Without those details, neither the endpoint nor its result can be reconstructed from the adverse-event counts.
The study is listed as non-randomized and single-group, with no separate control. The cohorts differ in PF-00477736 dose or administration duration, and some differ in gemcitabine dose. Cohort comparisons are therefore descriptive and may be affected by allocation and other differences that the record does not characterize. The cohort sizes are limited, and the registry does not provide uncertainty intervals for the adverse-event counts.
Although enrollment is recorded as 43, the number in the full analysis set is not reported. The record does not explain how missing or incomplete outcome data were handled, nor does it describe the analysis population for each secondary outcome. It lists 11 outcome measures but records 0 analyses, leaving no numerical response or pharmacokinetic findings to interpret.
The record also gives no reason for termination, no detailed statistical analysis plan, and no account of interim analyses. These aspects are not reported in the registry record and should not be guessed. For safety interpretation, the term-level percentages lack stated denominator context, and the death field is not reported. The listed serious-event term “Sudden death” does not resolve that missing information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: PF-00477736 Is Being Studied In Advanced Solid Tumors In Combination With Chemotherapy With Gemcitabine — NCT00437203.
- Registry record last updated 2012-04-03; status last verified 2012-03.
- Results first posted 2012-04-03.
- 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.
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18. Record Summary
The registry describes NCT00437203 as a Phase I study of PF-00477736 with gemcitabine in patients with advanced solid malignancies. It was non-randomized, unmasked, and single-group, with enrollment of 43. The study is listed as terminated; its start is recorded as 2006-12 and primary completion as 2011-04.
The primary endpoint was maximum tolerated dose of PF-00477736 with gemcitabine, measured in mg through Day 21 of Cycle 1. The full analysis set included enrolled participants who received at least 1 dose of study medication. The registry record does not report the primary-endpoint result, an analysis, or the reason for termination.
The record lists 11 outcome measures and 0 analyses. It reports adverse-event counts by cohort and several serious-event terms with reported percentages. The available results do not establish a comparative treatment effect or identify a maximum tolerated dose.