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 A Study Of PF-06664178 In Patients With Advanced Solid Tumors (NCT02122146), a registered phase 1 study. The primary outcome is First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02122146 |
| Phase | Phase 1 |
| Condition | Neoplasms |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | None (open label) |
| Enrollment | 31 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Patients with locally advanced or metastatic solid tumors. The registry record reports 31 enrolled participants and describes the primary endpoint population as all enrolled participants who started treatment.
Intervention
PF-06664178, administered at escalating dose levels. The record identifies dose groups from 0.15 mg/kg through 4.80 mg/kg.
Comparator
No separate control treatment is described. The record lists PF-06664178 intervention entries and dose groups; allocation is not stated, and the arms are not a like-for-like control comparison.
Primary question
How many participants experienced a dose-limiting toxicity at each dose level during the first cycle, to inform determination of the maximum tolerated dose?
This is a dose-escalation safety question rather than a comparison of PF-06664178 with another treatment. The trial’s brief summary says the aim was to assess safety and tolerability at increasing dose levels, determine the maximum tolerated dose, and select a recommended Phase 2 dose. The primary endpoint counts participants with dose-limiting toxicities at a given dose level. The registry record does not report those counts by dose or state a maximum tolerated dose or recommended Phase 2 dose.
The record also lists outcomes concerning treatment-emergent adverse events, laboratory abnormalities, anti-PF-06664178 antibodies, objective tumor response, and plasma concentrations. These outcomes broaden the safety, immunogenicity, activity, and pharmacokinetic description, but do not turn the study into a controlled efficacy comparison. Results for the primary endpoint and most other listed outcomes are not reported in the registry record.
3. Trial Design
NCT02122146 is listed as a Phase 1 study of PF-06664178 in patients with advanced solid tumors. Its official title describes a dose-escalation study in locally advanced or metastatic solid tumors. Pfizer is identified as the sponsor. The trial began in 2014-08, had primary completion in 2016-06, and is recorded as terminated. The reason for termination is not reported in the registry record.
The registry reports enrollment of 31 participants and identifies the study as unmasked. It does not state allocation, and no randomized control comparison is described. Dose groups listed in the safety record range from PF-06664178 0.15 mg/kg to PF-06664178 4.80 mg/kg. The study’s stated purpose was to assess safety and tolerability across increasing dose levels and use that information to determine the maximum tolerated dose and select a recommended Phase 2 dose. The registry record does not report the dose-escalation rules, the number of planned cohorts, or how decisions to increase or stop dosing were made.
The primary endpoint is the number of participants with dose-limiting toxicities from Day 1 up to Day 21. Its stated population is all enrolled participants who started treatment. The registry notes that a participant in the 4.80 mg/kg group had a late dose-limiting toxicity at the beginning of Cycle 2, classified as a late DLT. The record does not explain how that late event was incorporated into the primary endpoint summary.
The listed secondary outcomes include adverse events, laboratory abnormalities, anti-drug antibodies, objective tumor response, and maximum observed plasma concentrations. Although the record lists 28 outcome measures, it reports zero analyses. That combination means the outcome inventory is broader than the results available for statistical interpretation.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: A total of 38 patients were screened, among which 31 were assigned to study treatment.
Only the first 6 of 8 groups are shown.
Part 1: Dose Escalation
| Stage | PF-06664178 0.15 mg/kg | PF-06664178 0.30 mg/kg | PF-06664178 0.60 mg/kg | PF-06664178 1.20 mg/kg | PF-06664178 2.40 mg/kg | PF-06664178 3.60 mg/kg |
|---|---|---|---|---|---|---|
| STARTED | 2 | 2 | 4 | 4 | 4 | 6 |
| COMPLETED | 1 | 1 | 2 | 3 | 3 | 5 |
| NOT COMPLETED | 1 | 1 | 2 | 1 | 1 | 1 |
Reasons for not completing this period:
| Reason | PF-06664178 0.15 mg/kg | PF-06664178 0.30 mg/kg | PF-06664178 0.60 mg/kg | PF-06664178 1.20 mg/kg | PF-06664178 2.40 mg/kg | PF-06664178 3.60 mg/kg |
|---|---|---|---|---|---|---|
| Death | 0 | 1 | 1 | 0 | 0 | 0 |
| Lost to Follow-up | 0 | 0 | 1 | 0 | 1 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
| Other | 1 | 0 | 0 | 0 | 0 | 1 |
Part 2: Maximum Tolerated Dose
| Stage | PF-06664178 0.15 mg/kg | PF-06664178 0.30 mg/kg | PF-06664178 0.60 mg/kg | PF-06664178 1.20 mg/kg | PF-06664178 2.40 mg/kg | PF-06664178 3.60 mg/kg |
|---|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Part 3: Expansion
| Stage | PF-06664178 0.15 mg/kg | PF-06664178 0.30 mg/kg | PF-06664178 0.60 mg/kg | PF-06664178 1.20 mg/kg | PF-06664178 2.40 mg/kg | PF-06664178 3.60 mg/kg |
|---|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All enrolled participants who started treatment. One of participants that experienced DLTs in PF-06664178 4.80mg/kg group was a late DLT that occurred at the beginning of Cycle 2 and was classified as a late DLT.
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 9 groups are shown.
| Characteristic | Unit | PF-06664178 0.15 mg/kg | PF-06664178 0.30 mg/kg | PF-06664178 0.60 mg/kg | PF-06664178 1.20 mg/kg | PF-06664178 2.40 mg/kg | PF-06664178 3.60 mg/kg |
|---|---|---|---|---|---|---|---|
| Participants analysed | 2 | 2 | 4 | 4 | 4 | 6 | |
| Age, Continuous | years | 54 (SD 7.1) | 75 (SD 11.3) | 61 (SD 17.9) | 52.8 (SD 20) | 46 (SD 11) | 53.7 (SD 11.8) |
| Sex: Female, Male: Female | Participants | 1 | 0 | 2 | 2 | 1 | 5 |
| Sex: Female, Male: Male | Participants | 1 | 2 | 2 | 2 | 3 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as First Cycle Dose Limiting Toxicities (DLTs) In Order to Determine the Maximum Tolerated Dose(MTD), measured over Day 1 up to Day 21.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants who experienced a dose-limiting toxicity at a given dose level. Its stated timeframe is Day 1 up to Day 21, and its unit is participants. In early dose-escalation research, this type of endpoint helps describe whether toxicities considered dose-limiting occur during the initial treatment period at each dose. The pattern across dose groups can inform decisions about tolerability and further dose selection. This is a general description of the role of such an endpoint, not a claim about the findings of this trial.
The registry record states that the endpoint was intended to support determination of the maximum tolerated dose. It does not give the operational definition of a dose-limiting toxicity, the criteria for judging an event as dose-limiting, or the decision rule used to identify a maximum tolerated dose. Those details are not reported in the registry record, so the endpoint’s classification and decision process cannot be reconstructed from the record.
The specified population includes all enrolled participants who started treatment. The number who started treatment is not separately reported in the registry record. A late DLT in the 4.80 mg/kg group occurred at the beginning of Cycle 2 and is explicitly classified as a late DLT. Since the primary timeframe is Day 1 up to Day 21, that note is relevant to interpretation, but the record does not explain whether or how the late event was included in the primary endpoint results.
Most importantly, the primary endpoint’s participant counts by dose level are not reported in the registry record. Without those counts, it is not possible to describe the observed first-cycle DLT pattern or infer a dose-specific maximum tolerated dose from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study’s purpose and describes its endpoint, but it does not report the primary endpoint results. Although the endpoint is defined as the number of participants with dose-limiting toxicities at each dose level, no dose-specific counts are posted. Therefore, the frequency or pattern of first-cycle DLTs cannot be described from the record, and no maximum tolerated dose or recommended Phase 2 dose can be identified from the posted results.
The safety information that is reported gives counts of participants with serious adverse events and counts with other adverse events across dose groups. In the total row, serious adverse events are reported for 13 of 31 participants at risk, while other adverse events are reported for 31 of 31 participants at risk. These are descriptive participant counts. They do not by themselves establish that an event was caused by PF-06664178, nor do they provide a comparison with an untreated or active-control group. The registry record does not provide a randomized control comparison.
Serious adverse event counts differ across the dose groups, but the group sizes also differ. These are small dose cohorts, and a count from a small group can change substantially with the experience of a participant. Without a control group, adjustment for other factors, or a reported analysis plan, the group counts should not be interpreted as a comparative estimate of dose-specific risk. They also do not describe event timing, duration, recurrence, or severity beyond the serious classification.
The registry lists serious-event terms including dyspnoea, dehydration, disease progression, mucosal inflammation, pain, and pneumonia, with percentages among the posted serious-event terms. Those terms describe the event categories reported, not a causal attribution. Disease progression is among the listed terms, which is a reminder that events during a cancer trial may reflect the underlying disease as well as treatment or other causes. The registry’s term-level reporting does not resolve attribution.
For the primary question, the available record is therefore incomplete: it documents that the endpoint was selected to support dose finding, but does not provide the endpoint results needed to evaluate the observed dose-limiting toxicity pattern. Safety counts can be read as descriptive observations in the enrolled groups, not as evidence of a treatment effect. The study status is terminated, but the reason for termination is not reported in the registry record; status alone does not explain the endpoint findings or establish why the study ended.
9. Statistical Methods Explained
For a dose-escalation study, the central statistical task is usually to characterize toxicity at each dose and use that information to guide subsequent dosing decisions. The primary endpoint in this record is a count of participants with DLTs at a given dose level during Day 1 up to Day 21. That is a participant-level binary outcome: each participant either meets the DLT definition for the endpoint or does not. The registry gives the outcome unit and timeframe, but the DLT criteria and dose-escalation decision rule are not reported in the registry record.
What do participant counts convey?
A count tells how many participants in a group experienced an event. Its interpretation depends on the number of participants who could have experienced that event, the definition of the event, and the period during which it was assessed. The safety record gives the numbers at risk and affected for serious and other adverse events. Those counts support a direct description of observed participants, but they do not establish causality or provide a comparison against a control group. General statistical point: counts from small groups are imprecise descriptions of the broader population, because the observed participants may not represent the full range of outcomes that could occur.
The record’s primary endpoint population is all enrolled participants who started treatment. It does not separately report how many enrolled participants started treatment or how endpoint evaluability was handled. In general, a clearly described analysis population helps readers understand who contributed to an endpoint and how participants with incomplete assessments were treated. Those operational details are not reported in the registry record.
What can be inferred from differences among dose groups?
The listed dose cohorts have different sizes, and there is no randomized control comparison. General statistical point: observed counts across groups can reflect differences in group size, participant characteristics, follow-up, or chance, as well as any relation to dose. A numerical contrast between dose groups would not, on its own, isolate a dose effect. The record does not report a model, an adjusted estimate, a confidence interval, a hypothesis test, or a formal trend analysis. It also reports zero analyses. Consequently, there is no posted inferential result to interpret as an estimate of uncertainty or evidence for a dose-response pattern.
A confidence interval, in general, expresses uncertainty around an estimated quantity under a specified statistical method. No confidence interval for the primary endpoint or adverse-event counts is reported in the registry record. A p-value, in general, summarizes how compatible data are with a specified null hypothesis under a model; it is not a measure of clinical importance or the probability that a hypothesis is true. No p-value for the primary endpoint is reported in the registry record. In the absence of these analyses, interpretation should remain descriptive.
How should planning calculations be read?
The stated sample-size assumptions describe a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also describe planning for a stated fraction of the observed effect. Such calculations are not an observed power analysis, and a planning illustration is not evidence that the trial was designed or powered to answer a particular question. The registry record does not report a sample-size justification for this dose-escalation study or identify a control-arm comparison that matches those planning assumptions. The listed assumptions should therefore not be read as the trial’s documented design rationale.
More generally, power is a design quantity linked to assumptions about the outcome, effect, variability, allocation, and analysis. It does not describe the probability that a result is true after the data have been collected. A sample-size calculation based on a post hoc observed effect can be especially difficult to interpret as a design justification because the effect estimate itself is uncertain. These are general statistical considerations, not additional findings from this trial.
Why does over-dispersion matter?
Over-dispersion is a general concern when observed variation in count data is greater than a statistical model expects. It can make standard errors too small if the model assumes less variability than the data contain, and can lead to overly narrow uncertainty intervals or misleading tests. This endpoint is a participant count within dose cohorts, and the registry record does not report a count model or a dispersion assessment. There is no basis in the posted results to claim that over-dispersion was assessed or present. For a small dose-escalation study, transparent cohort counts and endpoint definitions are particularly important because complex modeling cannot substitute for missing outcome detail.
The endpoint timeframe also matters. The primary measure covers Day 1 up to Day 21, while the registry separately identifies a late DLT at the beginning of Cycle 2 in the 4.80 mg/kg group. The record calls this event late, but does not describe how it was used in dose decisions or whether it appears in the primary endpoint count. General statistical point: outcomes assessed outside a prespecified window may need distinct handling to preserve a consistent endpoint definition. The actual handling in this trial is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists multiple outcome measures, including the primary DLT endpoint and secondary outcomes covering treatment-emergent adverse events, laboratory abnormalities, anti-PF-06664178 antibodies, objective tumor response, and plasma concentrations. It does not report an analysis plan describing how these outcomes were prioritized, how repeated comparisons were handled, or whether any adjustment for multiplicity was planned. Those methods are not reported in the registry record.
Multiplicity is a general statistical issue that arises when several hypotheses or endpoints are examined: the chance of at least one apparently notable finding can increase when many tests are conducted. Whether adjustment is appropriate depends on the purpose and structure of the analyses. In a dose-escalation study, some outcomes may be primarily descriptive, but the registry does not state how the listed outcomes were intended to be analyzed. The record reports zero analyses, and the primary endpoint results are not posted, so there are no reported tests to evaluate for multiplicity.
Missing-data methods are also not reported in the registry record. The primary endpoint population is described as all enrolled participants who started treatment, but the number who started treatment is not separately given, nor are the numbers with evaluable DLT assessments or any rules for incomplete observation. The record does not say how participants who stopped treatment early, missed assessments, or had unevaluable data were handled. These omissions limit assessment of whether the endpoint population and follow-up were applied consistently.
The record identifies the primary endpoint population but does not provide a broader analysis-population description for the secondary outcomes. It does not report whether the analyses used all enrolled participants, treated participants, evaluable participants, or another population. No imputation approach or sensitivity analysis is reported in the registry record. As a result, readers cannot assess the impact of missing or incomplete observations on the posted endpoint estimates.
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-06664178 0.15 mg/kg | 0 | 2 | 0.0% |
| PF-06664178 0.30 mg/kg | 1 | 2 | 50.0% |
| PF-06664178 0.60 mg/kg | 2 | 4 | 50.0% |
| PF-06664178 1.20 mg/kg | 0 | 4 | 0.0% |
| PF-06664178 2.40 mg/kg | 1 | 4 | 25.0% |
| PF-06664178 3.60 mg/kg | 3 | 6 | 50.0% |
| PF-06664178 4.20 mg/kg | 1 | 1 | 100.0% |
| PF-06664178 4.80 mg/kg | 5 | 8 | 62.5% |
| Total | 13 | 31 | 41.9% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| PF-06664178 0.15 mg/kg | 2 of 2 |
| PF-06664178 0.30 mg/kg | 2 of 2 |
| PF-06664178 0.60 mg/kg | 4 of 4 |
| PF-06664178 1.20 mg/kg | 4 of 4 |
| PF-06664178 2.40 mg/kg | 4 of 4 |
| PF-06664178 3.60 mg/kg | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | PF-06664178 0.15 mg/kg | PF-06664178 0.30 mg/kg | PF-06664178 0.60 mg/kg | PF-06664178 1.20 mg/kg | PF-06664178 2.40 mg/kg | PF-06664178 3.60 mg/kg |
|---|---|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 0 of 2 | 0 of 2 | 0 of 4 | 0 of 4 | 0 of 4 | 1 of 6 |
| Disease progression | General disorders | 0 of 2 | 0 of 2 | 1 of 4 | 0 of 4 | 0 of 4 | 0 of 6 |
| Mucosal inflammation | General disorders | 0 of 2 | 0 of 2 | 0 of 4 | 0 of 4 | 0 of 4 | 1 of 6 |
| Pain | General disorders | 0 of 2 | 0 of 2 | 0 of 4 | 0 of 4 | 1 of 4 | 0 of 6 |
| Pneumonia | Infections and infestations | 0 of 2 | 0 of 2 | 1 of 4 | 0 of 4 | 0 of 4 | 0 of 6 |
| Urinary tract infection | Infections and infestations | 0 of 2 | 0 of 2 | 0 of 4 | 0 of 4 | 0 of 4 | 1 of 6 |
| Dehydration | Metabolism and nutrition disorders | 0 of 2 | 1 of 2 | 0 of 4 | 0 of 4 | 0 of 4 | 0 of 6 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 0 of 2 | 0 of 2 | 1 of 4 | 0 of 4 | 0 of 4 | 0 of 6 |
| Malignant pleural effusion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 2 | 0 of 2 | 0 of 4 | 0 of 4 | 0 of 4 | 1 of 6 |
| Seizure | Nervous system disorders | 0 of 2 | 0 of 2 | 0 of 4 | 0 of 4 | 0 of 4 | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | PF-06664178 0.15 mg/kg | PF-06664178 0.30 mg/kg | PF-06664178 0.60 mg/kg | PF-06664178 1.20 mg/kg | PF-06664178 2.40 mg/kg | PF-06664178 3.60 mg/kg |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 0 of 2 | 0 of 2 | 3 of 4 | 1 of 4 | 1 of 4 | 4 of 6 |
| Nausea | Gastrointestinal disorders | 0 of 2 | 0 of 2 | 2 of 4 | 0 of 4 | 2 of 4 | 3 of 6 |
| Constipation | Gastrointestinal disorders | 0 of 2 | 0 of 2 | 2 of 4 | 1 of 4 | 2 of 4 | 1 of 6 |
| Diarrhoea | Gastrointestinal disorders | 0 of 2 | 0 of 2 | 2 of 4 | 0 of 4 | 2 of 4 | 2 of 6 |
| Infusion related reaction | Injury, poisoning and procedural complications | 0 of 2 | 0 of 2 | 0 of 4 | 1 of 4 | 1 of 4 | 4 of 6 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 2 | 1 of 2 | 3 of 4 | 0 of 4 | 1 of 4 | 1 of 6 |
| Chills | General disorders | 0 of 2 | 1 of 2 | 0 of 4 | 0 of 4 | 1 of 4 | 3 of 6 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 0 of 2 | 0 of 2 | 2 of 4 | 1 of 4 | 0 of 4 | 2 of 6 |
| Back pain | Musculoskeletal and connective tissue disorders | 1 of 2 | 0 of 2 | 3 of 4 | 0 of 4 | 1 of 4 | 0 of 6 |
| Anaemia | Blood and lymphatic system disorders | 0 of 2 | 0 of 2 | 1 of 4 | 1 of 4 | 1 of 4 | 1 of 6 |
Serious events with the highest arm-level rate: dyspnoea (100.0%), dehydration (50.0%), disease progression (25.0%), mucosal inflammation (25.0%), pain (25.0%).
The safety record reports participants at risk and participants affected for serious and other adverse events. Across all dose groups, serious adverse events were reported for 13 of 31 participants at risk; other adverse events were reported for 31 of 31 participants at risk. By dose group, the serious-event counts are 0 of 2 at 0.15 mg/kg, 1 of 2 at 0.30 mg/kg, 2 of 4 at 0.60 mg/kg, 0 of 4 at 1.20 mg/kg, 1 of 4 at 2.40 mg/kg, 3 of 6 at 3.60 mg/kg, 1 of 1 at 4.20 mg/kg, and 5 of 8 at 4.80 mg/kg. These are participant counts, not event counts.
The listed serious adverse event terms are dyspnoea (100.0%), dehydration (50.0%), disease progression (25.0%), mucosal inflammation (25.0%), pain (25.0%), and pneumonia (25.0%). The registry record does not provide enough detail in these figures to establish that PF-06664178 caused the events, or to compare event rates against another treatment. Serious-event definitions, event timing, and attribution methods are not reported in the registry record. Death counts are not reported in the registry record.
These data are best read as descriptive safety observations among participants in each dose cohort. The cohorts are small and differ in size, and the study does not describe a control group. The counts do not establish a dose-related pattern or an estimate of comparative risk.
12. What the Result Does, and Does Not, Mean
The record documents a Phase 1 dose-escalation study designed to assess safety and tolerability of PF-06664178 in patients with advanced solid tumors. It identifies the primary endpoint as the number of participants with DLTs at each dose level during Day 1 up to Day 21, and states that the endpoint was intended to support maximum tolerated dose determination. It also posts participant counts for serious and other adverse events. These details describe the study’s questions and some observed safety events.
However, the primary DLT counts by dose are not reported in the registry record. The maximum tolerated dose and recommended Phase 2 dose are not reported either. There is no posted inferential analysis, confidence interval, or p-value for the primary endpoint. The record therefore does not permit a statistical assessment of the observed DLT pattern, its precision, or the uncertainty around dose selection.
The serious and other adverse-event counts do not constitute a controlled comparison. They are descriptive counts in the listed PF-06664178 groups, not estimates of how outcomes would differ under another treatment. The record does not state that the groups were randomized, and no like-for-like control arm is described. Event counts also do not establish causality; the listed adverse events may have multiple possible causes, and attribution detail is not reported.
The trial status is terminated, but the reason for termination is not reported in the registry record. It would be inappropriate to infer the reason from the status alone or to treat termination as evidence for or against a treatment effect. Likewise, the absence of posted primary endpoint results is not evidence that no DLTs occurred; the record simply does not report the dose-specific results.
In general, early dose-escalation findings can inform later research by describing observed toxicities at studied doses. That general role does not establish efficacy or safety beyond the participants and observations reported. Here, the limited outcome reporting and lack of an inferential analysis constrain what can be concluded from the registry record.
13. Why This Trial Matters Statistically
This trial illustrates an important statistical distinction between a study’s stated objective and the results available for evaluating it. The registry identifies dose-limiting toxicity as the primary endpoint and explains its role in determining a maximum tolerated dose, but does not report the dose-specific DLT counts. Without those counts, the central dose-finding question cannot be answered from the posted results. A clearly defined endpoint is necessary for interpretation, but definition alone is not a result.
The safety record also illustrates why participant counts require context. The dose groups have differing sizes, so a count in one cohort is not directly comparable to a count in another without considering the denominators and the study design. Since there is no reported control comparison or inferential analysis, these data support description rather than a causal or comparative claim. This distinction matters especially in small dose cohorts, where individual observations have substantial influence on the observed group counts.
The record further shows how reporting of endpoints, analysis populations, and event handling affects reproducibility. The primary timeframe is stated, and a late DLT is noted, but the record does not explain how that event was incorporated into the primary analysis. The operational DLT definition, missing-data handling, dose-escalation rules, and analysis methods are not reported. These details would be needed to understand how raw observations informed dose decisions.
Finally, a trial status and a list of safety outcomes are not substitutes for complete results. The terminated status does not explain why the study ended, and serious adverse-event counts do not by themselves indicate causality. The statistical lesson is to separate what the record documents, what it leaves unreported, and what can only be discussed as general methodology.
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 most consequential limitation of the registry record is that it does not report the primary endpoint counts by dose level. The study’s stated purpose was dose finding, but the posted results do not show the DLT pattern needed to assess that purpose or identify a maximum tolerated dose. The recommended Phase 2 dose is also not reported in the registry record.
The record does not define the criteria for a DLT or describe the dose-escalation rules. It notes a late DLT at the beginning of Cycle 2 in the 4.80 mg/kg group, but does not explain how that event was handled in relation to the primary timeframe of Day 1 up to Day 21. The number of enrolled participants who started treatment is not separately reported, although the primary endpoint population is described as participants who started treatment.
Other key design and analysis details are not reported in the registry record. These include the reason for termination, allocation procedures, a statistical analysis plan, handling of missing or unevaluable endpoint data, and the analysis populations for secondary outcomes. The record reports zero analyses, so there are no inferential estimates or uncertainty measures to evaluate. A sample-size justification for the dose-escalation study is not reported.
Safety reporting is descriptive and lacks a control comparison. The serious-event figures do not establish attribution, and detail on event timing and severity beyond the serious classification is not reported. The term-level figures do not provide enough information to assess recurrence or how event categories were assigned. These limitations restrict interpretation to the reported participant counts and prevent conclusions about comparative risk or causality.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study Of PF-06664178 In Patients With Advanced Solid Tumors — NCT02122146.
- Registry record last updated 2018-02-19; status last verified 2017-08.
- Results first posted 2018-02-19.
- 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
NCT02122146 is a Phase 1, unmasked dose-escalation study of PF-06664178 in patients with locally advanced or metastatic solid tumors. Pfizer is the sponsor. The record reports 31 enrolled participants, a start date of 2014-08, primary completion in 2016-06, and a status of terminated. The reason for termination is not reported in the registry record.
The primary endpoint counts participants with dose-limiting toxicities at each dose level from Day 1 up to Day 21. The record states that the endpoint population comprises enrolled participants who started treatment and notes a late DLT at the beginning of Cycle 2 in the 4.80 mg/kg group. Primary endpoint counts by dose, maximum tolerated dose, and recommended Phase 2 dose are not reported.
Safety counts are posted for serious and other adverse events. The record lists 28 outcome measures and reports zero analyses. Methods for missing data, multiplicity, and statistical inference are not reported in the registry record.