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 Docetaxel With or Without FGFR Inhibitor AZD4547 in Treating Patients With Recurrent Non-Small Cell Lung Cancer (NCT01824901), a randomized phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose (MTD) of FGFR Inhibitor AZD4547.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01824901 |
| Phase | Phase 1, Phase 2 |
| Condition | Recurrent Non-small Cell Lung Cancer, Squamous Cell Lung Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | ECOG-ACRIN Cancer Research Group |
| Results posted | Yes |
2. Clinical Question
The study concerns recurrent squamous non-small cell lung cancer described as FGFR1-amplified. Its phase I component examined AZD4547 dose levels alongside docetaxel, while the phase II component was designed to compare docetaxel alone with docetaxel plus AZD4547. The registry record also describes AZD4547 treatment after disease progression in a phase II step II; details of that treatment schedule are incomplete in the record.
Population
Patients with recurrent FGFR1-amplified squamous non-small cell lung cancer. The registry record does not report further eligibility details in the primary endpoint description.
Intervention
AZD4547 with docetaxel in the phase I dose-finding component and in phase II Arm II. AZD4547 was described as an FGFR inhibitor.
Comparator
Docetaxel alone in phase II Arm I. The study title and design describe a comparison with docetaxel plus AZD4547.
Primary question
What maximum tolerated dose of AZD4547 should be recommended for phase II when given with docetaxel? The endpoint was assessed during cycle 1, and the registry record does not report an MTD result.
The registry record describes the study as a phase I/randomized phase II trial, with randomized allocation, no masking, and a parallel model. These design features do not by themselves establish how many participants entered each phase or arm. Enrollment is recorded as 2, and no arm-specific efficacy analysis is listed. Accordingly, the central inferential question is described by the protocol, but the posted results do not provide an estimate of comparative treatment effect.
3. Trial Design
The study is identified as a phase I/randomized phase II trial. The phase I component was intended to evaluate AZD4547 dose levels in combination with a standard dose of docetaxel. Three AZD4547 dose levels were planned: 40mg, 60mg, and 80mg, with a starting dose of 40 mg. The phase I dose-finding plan used a standard 3+3 design, enrolling patients in cohorts of 3. The registry record defines the MTD as the highest dose level at which less than or equal to 1 of 6 subjects experience dose limiting toxicity.
The phase II component is described as randomized, unmasked, and parallel. Arm I received docetaxel, with treatment planned every 21 days for up to 6 courses, unless disease progression or unacceptable toxicity occurred. Arm II received docetaxel and AZD4547, also on a 21-day cycle and for up to 6 courses unless progression or unacceptable toxicity occurred. The description specifies docetaxel IV over 60 minutes on day 1; AZD4547 was taken by mouth twice daily on days 1-14 in Arm II.
The record also describes a phase II step II in which patients received AZD4547, and says that patients with progressive disease in Arm I could register for step II. The schedule at the end of the Arm I step II description is truncated, so its precise instructions are not reported in the registry record. The phase I schedule differs from the phase II Arm II schedule: AZD4547 was given on days 2-15 of course 1 and days 1-14 of later courses in phase I.
Recorded enrollment is 2. The registry record does not report how this enrollment was distributed among dose cohorts, study phases, or randomized arms. It also does not report the randomization procedure, allocation concealment, or the number assigned to each phase II arm. The study is marked completed, with start and primary completion dates recorded, but those dates do not establish when individual participants were enrolled or assessed.
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.
Overall Study
| Stage | Phase I | Arm I (Docetaxel; Phase II Step I) | Arm II (Docetaxel and AZD4547; Phase II Step I) | Phase II Step II |
|---|---|---|---|---|
| STARTED | 2 | 0 | 0 | 0 |
| COMPLETED | 2 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
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.
| Characteristic | Unit | Phase I |
|---|---|---|
| Participants analysed | 2 | |
| Age, Continuous | years | 66.5 (56 to 77) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of FGFR Inhibitor AZD4547, measured over Assessed during cycle 1 (21 days).
| 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 (MTD) of AZD4547, measured in mg and assessed during cycle 1 (21 days). This is a dose-finding endpoint rather than a measure of comparative tumor response or survival. The phase I plan tested AZD4547 in combination with docetaxel and defined the MTD as the highest planned dose level at which less than or equal to 1 of 6 subjects experience dose limiting toxicity. That definition links the endpoint to tolerability during the specified assessment period.
In general, a dose-finding study uses early safety observations to identify a dose that can be carried forward for later study. The MTD is useful for this purpose because it is a prespecified decision criterion based on dose limiting toxicity, rather than an estimate of whether one treatment is more effective than another. The record says that the intended MTD was to be recommended for the phase II portion.
The registry record does not report the observed dose limiting toxicities by dose level, the number assessed at each level, or a selected MTD. It therefore does not provide a reported endpoint value or enough participant-level or cohort-level information to reconstruct one. The endpoint description states what was planned; it should not be read as a posted result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes an early dose-finding question and a later randomized comparison, but the posted outcome information does not establish a primary endpoint result. The one listed primary outcome is MTD, and there are no analyses listed. No selected AZD4547 dose, dose-specific toxicity count, or confidence interval for the MTD is reported in the registry record. The definition and planned dose levels are available, but they are not substitutes for observations.
Enrollment is recorded as 2. This is a small recorded enrollment relative to the phase I plan to enroll cohorts of 3 and the MTD definition’s reference to 6 subjects at a dose level. The record does not say how the 2 enrolled participants were treated, whether they completed cycle 1, which dose levels they received, or whether they were evaluable for dose limiting toxicity. Therefore, the enrollment number alone cannot show whether the MTD decision rule was applied.
The phase II study design is described as a randomized comparison of docetaxel alone and docetaxel with AZD4547. However, no phase II outcome analysis is listed. There is no posted estimate of a treatment difference, uncertainty interval, or test of comparative efficacy. The record's design description explains the intended comparison but does not demonstrate that a comparison was completed or what it found. A sample-size illustration based on an observed effect cannot be generated from a primary comparison that has no reported analysis.
The adverse-event information is also limited. The Phase I group lists 2 participants at risk for serious events and 2 affected; for other events, it also lists 2 at risk and 2 affected. The serious adverse event terms include several entries reported at 100.0%, and other terms at 50.0%. With only 2 recorded participants in the listed group, these percentages represent a very limited amount of information and should not be treated as stable estimates of event frequency in a broader population. The registry record does not report the event-level details needed to interpret timing, severity grading, recurrence, or attribution.
These data describe what was registered and posted, not the full evidence base for the treatments. The record does not report a treatment effect estimate, a completed analysis plan, or the details needed to assess precision for clinical outcomes. Statistical interpretation should therefore stay focused on the planned MTD method, the small recorded enrollment, and the absence of outcome analyses, without inferring efficacy or safety beyond the listed information.
9. Statistical Methods Explained
The study combines dose finding with a planned randomized comparison, and the methods have different purposes in those components. Phase I was intended to identify a dose of AZD4547 for use with docetaxel. Phase II was designed to compare docetaxel alone with docetaxel plus AZD4547. The registry record identifies the overall study as randomized, unmasked, and parallel, but does not describe which randomization procedure was used or provide phase II analysis results.
How does the 3+3 dose-finding plan work?
In general, a 3+3 design evaluates a dose in small cohorts and uses observed dose limiting toxicities to guide whether escalation, expansion, or stopping is appropriate. The registry record specifies cohorts of 3 and defines the MTD as the highest dose at which less than or equal to 1 of 6 subjects experience a dose limiting toxicity. This is a rule for selecting a dose based on toxicity observations; it is not a statistical test comparing the combination with docetaxel alone.
The listed plan starts at 40 mg of AZD4547 and includes 60mg and 80mg levels. The record says that AZD4547 was combined with a standard docetaxel dose of 75mg/m^2. It does not report participant counts at each dose, the number with dose limiting toxicity, whether any dose escalation occurred, or the dose selected. As a result, the planned rule cannot be applied from the posted outcome information.
What does the randomized phase II structure contribute?
In general, random allocation is intended to make treatment groups comparable on average with respect to measured and unmeasured characteristics, subject to the conduct and size of the trial. An unmasked study means that masking is not part of the recorded design. A parallel design assigns participants to treatment groups that proceed alongside one another rather than having each participant receive every assigned treatment in sequence. Those general properties explain the design labels, but they do not establish the quality of implementation or the balance of groups in this study.
The intended phase II contrast is docetaxel alone versus docetaxel with AZD4547. The posted record does not list phase II outcomes or an analysis for that contrast. There is therefore no treatment-effect estimate to interpret, and no reported uncertainty interval or hypothesis-test result. The phase I MTD outcome and phase II comparative outcomes answer different questions and should not be conflated.
Why do uncertainty intervals matter?
In general, a confidence interval expresses the range of values compatible with an estimate under a specified statistical model and sampling procedure. A narrow interval indicates greater precision than a wide interval, while neither width nor interval location alone establishes the relevance of a result. No confidence interval for the MTD or for a phase II treatment effect is reported in the registry record. The absence of such an interval means that the precision of any primary endpoint estimate cannot be assessed from the posted results.
Likewise, a p-value, if reported, would describe how compatible the observed data are with a specified null model under the test’s assumptions. It would not by itself describe the magnitude or clinical importance of an effect. No phase II analysis or p-value is listed. It would be inappropriate to infer statistical significance or lack of significance from the design description or enrollment number.
How should planning illustrations be understood?
In general, a sample-size calculation uses assumptions about the effect to be detected, variability or event rates, allocation, significance level, and desired power. A planning illustration based on an observed effect is hypothetical: it asks how many participants might be needed under stated assumptions to detect an effect of a chosen size. It is not the number enrolled, evidence that the study had that power, or an estimate of what the study actually found.
The registry record states assumptions for a planning illustration: two-sided significance level 0.05, equal allocation between two arms, normal approximation, and effects defined as a stated fraction of the observed effect. However, the primary outcome is not a two-arm analysis and the record flags that there are fewer than two arms in the primary outcome. There is no posted primary comparison from which an observed effect can be used. Thus, those assumptions do not supply a sample-size result for the MTD endpoint or establish an observed power for this trial.
For outcomes analyzed as counts, rates, or event times, model choice and assumptions can matter. In general, over-dispersion occurs when variation in count data is greater than a model assumes; ignoring it can make uncertainty estimates too small. No count model, event-time analysis, dispersion estimate, or related result is reported for this study. These concepts describe possible statistical considerations, not methods that can be attributed to this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome measure, the MTD of AZD4547, and lists no analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, or a multiplicity adjustment. Therefore, it is not possible to determine whether multiple hypotheses or outcome comparisons were planned, how any such comparisons would have been controlled, or whether a prespecified analysis was changed. The phase II design includes two treatment groups, but no comparative outcome analysis is reported.
Missing-data methods are not reported in the registry record. There is no account of participants who withdrew, missed cycle 1 assessments, lacked toxicity evaluation, or were excluded from analysis. The record also does not report analysis populations, such as an intention-to-treat population or a safety population, or rules for determining whether participants were evaluable for dose limiting toxicity. With enrollment recorded as 2, details of the participant flow and assessment status are particularly important for judging what information was available, but they are not reported.
In general, missingness can affect estimates when participants without recorded outcomes differ from those with observed outcomes. The direction and size of that effect depend on why data are missing and on the analysis method. Since neither missingness details nor handling methods are reported, no conclusion about their impact can be drawn. The absence of this information does not prove that data were missing; it means the registry record does not describe their status or handling.
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 |
|---|---|---|---|
| Phase I | 2 | 2 | 100.0% |
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 |
|---|---|
| Phase I | 2 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase I |
|---|---|---|
| Lymphocyte count decreased | Investigations | 2 of 2 |
| Neutrophil count decreased | Investigations | 2 of 2 |
| White blood cell decreased | Investigations | 2 of 2 |
| Hypotension | Vascular disorders | 2 of 2 |
| Anemia | Blood and lymphatic system disorders | 1 of 2 |
| Myocardial infarction | Cardiac disorders | 1 of 2 |
| Left ventricular systolic dysfunction | Cardiac disorders | 1 of 2 |
| Multi-organ failure | General disorders | 1 of 2 |
| Dysphagia | Gastrointestinal disorders | 1 of 2 |
| Mucositis oral | Gastrointestinal disorders | 1 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase I |
|---|---|---|
| Fever | General disorders | 2 of 2 |
| Alanine aminotransferase increased | Investigations | 2 of 2 |
| Platelet count decreased | Investigations | 2 of 2 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 2 of 2 |
| Anemia | Blood and lymphatic system disorders | 1 of 2 |
| Fatigue | General disorders | 1 of 2 |
| Edema limbs | General disorders | 1 of 2 |
| Constipation | Gastrointestinal disorders | 1 of 2 |
| Vomiting | Gastrointestinal disorders | 1 of 2 |
| Mucosal infection | Infections and infestations | 1 of 2 |
Serious events with the highest arm-level rate: lymphocyte count decreased (100.0%), neutrophil count decreased (100.0%), white blood cell decreased (100.0%), hypotension (100.0%), anemia (50.0%).
The Phase I safety group lists 2 participants at risk for serious adverse events and 2 affected. For other adverse events, the group also lists 2 at risk and 2 affected. The record separately lists serious adverse event terms: lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hypotension are each reported at 100.0%; anemia and myocardial infarction are each reported at 50.0%.
These percentages should be read in the context of the small recorded group. They describe the registry entries, not reliable estimates of how often events occur in a larger population. The record does not provide event-level counts beside each term, details of event onset, duration, grade, recurrence, or investigator attribution. A participant may also contribute more than one event term, so term percentages should not be interpreted as a single overall event rate.
The number of deaths is not reported in the registry record. The listed adverse-event information alone does not support a comparison between treatment groups, because only a Phase I group is shown and no arm-level safety analysis is reported. In general, adverse-event counts describe observed events under the study’s reporting rules; they do not by themselves establish that a treatment caused an event.
12. What the Result Does, and Does Not, Mean
The posted information establishes that the study planned a phase I dose-finding component and a randomized phase II comparison of docetaxel alone with docetaxel plus AZD4547. It also establishes the MTD definition, the planned AZD4547 dose levels, the assessment period, the listed treatment schedules, and recorded enrollment of 2. These details help explain the intended design and the type of evidence the study was meant to produce.
The record does not establish an MTD result. It does not report dose limiting toxicity counts by dose, the number evaluable at each dose, or the recommended phase II dose. Nor does it report a phase II efficacy estimate, confidence interval, or analysis comparing the two arms. No conclusion about comparative treatment effects can be drawn from the design description alone.
The safety entries document the terms and percentages posted for the Phase I group, but the small recorded group and lack of event-level context limit interpretation. The entries do not establish population-level event rates or causation. The record does not report a death count.
In general, an absent analysis is not evidence that an effect is absent or that treatments are equivalent. Equivalence or noninferiority requires a suitable design and analysis with a prespecified margin, none of which is reported in the registry record. Likewise, an intended randomized comparison does not by itself establish that randomization was completed or that interpretable comparative data were collected.
The most defensible reading is therefore descriptive: the registry record documents a trial plan, limited enrollment, and a small set of safety entries, but does not present the primary outcome analysis or a comparative phase II result. Any statement that AZD4547 did or did not improve outcomes, or that one regimen was safer, would go beyond the reported evidence.
13. Why This Trial Matters Statistically
This trial is statistically notable because it combines two distinct inferential tasks. The phase I component uses a dose-finding rule to select a dose based on toxicity observed at planned dose levels. The randomized phase II component is intended to compare treatment strategies. Dose selection and comparative efficacy require different outcomes, analyses, and interpretations. Treating the MTD as if it were a phase II treatment-effect estimate would confuse the purpose of the two components.
The MTD definition is explicit: the selected dose is the highest dose at which less than or equal to 1 of 6 subjects experience dose limiting toxicity. That makes the decision rule understandable, but it also makes cohort-level observations central. The record reports enrollment of 2 without specifying dose assignments or evaluability, so the information needed to apply the rule is not available in the posted outcome record.
The statistical lesson is also one of reporting completeness. A randomized design can support a comparative question only when outcomes, analysis populations, effect estimates, and their uncertainty are reported. Here, the record describes the intended randomized comparison but lists no analyses. The absence of an effect estimate means neither magnitude nor precision can be assessed.
Finally, percentages from a group of 2 warrant particular caution. The figures are accurate descriptions of the record, but their denominator offers little basis for generalization. This distinction between a recorded percentage and a precise population estimate is important when interpreting safety reports from very small early-phase groups.
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 main trial-specific limitation is the mismatch between the recorded enrollment of 2 and the information needed to understand the planned dose-finding process. The registry record does not report how participants were assigned among the planned AZD4547 dose levels, whether they completed the cycle 1 assessment, or how many were evaluable for dose limiting toxicity. Without those details, the MTD rule cannot be independently assessed.
The primary endpoint is defined, but no result is reported. There are no posted dose-specific toxicity counts, MTD selection, or confidence interval. The randomized phase II design is described, yet no arm sizes, outcomes, comparative estimates, or analysis results are listed. Thus, the record does not permit an assessment of the intended between-arm comparison.
Additional design and analysis details are not reported in the registry record. These include the randomization procedure, analysis populations, missing-data handling, multiplicity strategy, and statistical analysis plan. The Arm I step II description is incomplete, and the registry record does not report how many participants entered that step. These omissions limit reconstruction of participant flow and treatment exposure.
Safety interpretation is constrained by the small Phase I group and by the lack of event-level detail. The record does not report the death count, individual event timing, severity grades, or attribution. The reported percentages should therefore remain descriptive rather than being generalized to a broader population. These limitations concern what can be learned from the registry record and do not, on their own, establish how the full study was conducted or reported elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Docetaxel With or Without FGFR Inhibitor AZD4547 in Treating Patients With Recurrent Non-Small Cell Lung Cancer — NCT01824901.
- Registry record last updated 2023-06-29; status last verified 2023-06.
- Results first posted 2016-03-01.
- 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 record describes NCT01824901 as a completed phase I/randomized phase II study of docetaxel with or without AZD4547 in recurrent FGFR1-amplified squamous non-small cell lung cancer. The overall design is listed as randomized, unmasked, and parallel, with enrollment of 2.
The primary outcome is the MTD of AZD4547, assessed during cycle 1 (21 days). The phase I plan lists dose levels of 40mg, 60mg, and 80mg and uses a 3+3 design. The registry record lists one outcome measure and no analyses. It does not report an MTD result or a phase II comparison.
Phase I safety entries list 2 participants at risk and 2 affected for serious events, and the same counts for other events. The record lists serious adverse event terms and percentages, but does not report a death count. The available information supports a description of the registered plan and posted entries, not a conclusion about comparative efficacy or broader safety.