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 MEK Inhibitor PD-0325901 Trial in Adolescents and Adults With NF1 (NCT02096471), a na phase 2 study. The primary outcome is Percent of Participants With a 20% or More Change in Target Tumor Volume.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02096471 |
| Phase | Phase 2 |
| Condition | Neurofibromatosis Type 1 and Growing or Symptomatic, Inoperable PN |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 19 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Alabama at Birmingham |
| Results posted | Yes |
2. Clinical Question
Population
Adolescents aged 16 years or older and adults with neurofibromatosis type 1 (NF1) and growing or symptomatic, inoperable plexiform neurofibromas (PN). The primary-outcome population is all 19 participants enrolled, described in the registry as equivalent to the intention-to-treat population.
Intervention
Oral PD-0325901. The protocol description specifies a dose of 2 mg/m2/dose, up to a maximum of 4 mg bid, in 4-week courses with a 3-week-on, 1-week-off schedule.
Comparator
There is no control group. The study is described as single group, with allocation marked NA and no masking.
Primary question
What proportion of participants had a 20% or greater change in target tumor volume, assessed using volumetric MRI from baseline through 24 months? The registry defines response categories, but the primary outcome result is not reported in the registry record.
The study addresses a radiographic question in participants with NF1 and growing or symptomatic, inoperable PN. Its stated primary purpose is to determine whether PD-0325901 is associated with objective responses measured from three-dimensional MRI scans of a target lesion. The protocol also describes secondary aims relating to feasibility and toxicity, response in up to 2 non-target plexiform neurofibromas, drug concentrations, and quality of life measures.
The design matters when interpreting the question. Because the trial is single group, its primary endpoint describes change in tumor volume among participants receiving the study drug. It does not make a randomized comparison with an untreated group or another treatment. The registry record does not report the number or percentage meeting the primary response definition, so the size and precision of the observed response cannot be assessed from the posted primary-outcome information.
3. Trial Design
This is a phase 2, open-label, single-group trial sponsored by the University of Alabama at Birmingham. The registry reports enrollment of 19 participants and a completed status. The recorded start is 2014-06, and primary completion is dated 2017-08-09. Allocation is listed as NA, and masking is listed as none. These design features mean there is no randomized comparator in the record and that participants and study personnel were not masked to treatment.
The eligible population is described as adolescents aged 16 years or older and adults with NF1 and growing or symptomatic, inoperable PN. Participants were to receive oral PD-0325901 at 2 mg/m2/dose, with a maximum dose of 4 mg bid. A course is described as 4 weeks, with drug taken on a 3-week-on, 1-week-off schedule. The protocol description allows additional courses beyond course 8 only when target-tumor volume has fallen by at least 15%. It describes continuing therapy for up to an additional year, to a maximum of 24 total courses, for participants whose target tumor volume has fallen by 20% or more at the end of 12 courses. Participants not reaching a 15% reduction after 8 courses are described as treatment failures and taken off study.
These details describe the protocol, not the treatment actually received by each participant. Individual exposure, adherence, treatment discontinuation, and the number of courses completed are not reported in the registry record. The primary endpoint is described over baseline to 24 months, with MRI assessments after course 4, course 8, course 12, and every 6 courses thereafter. The registry does not report the actual primary outcome result or the number of participants assessed at each scan time.
Secondary outcomes include toxicity, response in up to 2 non-target PN, pharmacokinetic measures for the parent and metabolite compounds, mean half-life, and quality-of-life assessments using pain and PedsQL NF1 instruments. The registry also identifies evaluable participants treated with PD-0325901 as a secondary outcome. The available information establishes the intended scope of assessment, but does not provide results for these outcomes.
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: The study required at least 1 partial or complete response within the first 9 patients in order to complete recruitment.
Overall Study
| Stage | Agent PD-0325901 |
|---|---|
| STARTED | 19 |
| COMPLETED | 6 |
| NOT COMPLETED | 13 |
Reasons for not completing this period:
| Reason | Agent PD-0325901 |
|---|---|
| Adverse Event | 1 |
| Lack of Efficacy | 7 |
| Withdrawal by Subject | 3 |
| Non-Compliant | 2 |
Analysis population for the primary outcome, as defined in the registry: All 19 participants enrolled equivalent to intention to treat population
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 | Agent PD-0325901 |
|---|---|---|
| Participants analysed | 19 | |
| Age, Categorical: <=18 years | Participants | 3 |
| Age, Categorical: Between 18 and 65 years | Participants | 16 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 24.9 (SD 6.4) |
| Sex: Female, Male: Female | Participants | 12 |
| Sex: Female, Male: Male | Participants | 7 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 16 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 5 |
| Race (NIH/OMB): White | Participants | 8 |
| Race (NIH/OMB): More than one race | Participants | 3 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | Participants | 19 |
| MRI at Baseline: 1 Target Number of Plexiform Neurofibromas | Participants | 17 |
| MRI at Baseline: 1 Target and non target Plexiform Neurofibromas | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Percent of Participants With a 20% or More Change in Target Tumor Volume, measured over baseline to 24 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percent of participants with a 20% or more change in target tumor volume, assessed from baseline to 24 months. The registry describes response assessment using follow-up three-dimensional MRI and comparison with the target lesion's pretreatment MRI volume. It defines complete response as complete resolution of the target PN for at least 4 weeks, partial response as a reduction in volume of at least 20% for at least 4 weeks, stable disease as a change involving less than a 20% increase and less than a 20% decrease for at least 4 weeks, and progressive disease as an increase of at least 20% compared with pretreatment volume.
Volumetric MRI is used in the protocol to quantify change in the target lesion rather than relying only on a qualitative impression. The repeated assessments described in the registry make it possible to evaluate tumor-volume status at specified points during treatment. The endpoint is a participant-level response measure: it concerns how many participants meet a defined response criterion, rather than the average volume change alone. The registry states that the NCI-POB assesses response when follow-up scans are performed.
However, the posted primary outcome information supplies the endpoint definition and timeframe without reporting the observed count or percentage. Consequently, the registry record does not report how many participants met any response category or how uncertain the estimated primary response proportion is. The endpoint definition clarifies what the study intended to measure, but cannot by itself establish the trial's observed result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The most important interpretive point is that the registry record describes how the primary endpoint was defined but does not report its result. Although the outcome is titled as the percent of participants with a 20% or more change in target tumor volume, no numerator, percentage, confidence interval, or test result is present in the primary outcome information. The registry record therefore does not report the observed primary response proportion. Without that result, it is not possible to characterize the magnitude or precision of the primary endpoint from the information available.
The study is single group, open label, and has no comparator. Its endpoint can describe tumor-volume changes observed during treatment, but the design does not separate those changes from what might have occurred without the study drug or under another treatment. General statistical interpretation: a control group can help distinguish treatment-associated change from changes arising from the natural course of disease, measurement variation, or other factors. In a single-group study, those alternative explanations cannot be addressed through a randomized between-group contrast.
The primary response definition is based on the target lesion and uses volumetric MRI. That makes the endpoint specific: it concerns a radiographic change in one target tumor, not necessarily change in every PN or in symptoms, function, or quality of life. The protocol separately lists non-target PN response and quality-of-life measures among its secondary outcomes. Their inclusion signals that the primary radiographic measure was not intended to encompass every relevant outcome. Results for those measures are not reported in the registry record.
The registry reports enrollment of 19 participants and states that all enrolled participants constitute the primary-outcome population, equivalent to intention to treat. That identifies the planned population for the primary analysis, but it does not establish how many had evaluable scans, how missing measurements were handled, or whether all enrolled participants contributed an endpoint value. Those details are not reported in the registry record. A small enrolled population also means that any response estimate, if available, would require careful attention to its uncertainty; the registry record does not report a confidence interval to quantify that uncertainty.
Safety information is reported separately. The registry lists 2 participants with serious adverse events among 19 at risk, and records 0 deaths. It also lists three serious-event terms, each with a reported frequency of 5.3%. These summaries should be read as registry safety descriptions, not as evidence that the events were caused by treatment. The record does not provide the details needed to assess timing, severity beyond the serious classification, attribution, or overlap between event terms.
Overall, the registry supplies a protocol-defined radiographic endpoint, a single-group design, and limited safety counts, but does not report the principal efficacy result. Statistical interpretation should therefore remain focused on what was measured and what the design can support, rather than inferring an effect from the study's objective or treatment rules.
9. Statistical Methods Explained
Statistical methods are easiest to interpret by separating the endpoint definition, the analysis population, the study design, and the information actually reported. In this trial, the endpoint is a participant-level target-tumor response classification based on volumetric MRI. The registry identifies all 19 enrolled participants as the primary-outcome population, equivalent to intention to treat. It does not report the primary response count, an interval estimate, or a statistical test result.
What does a participant-level response measure mean?
A participant-level response endpoint classifies each participant according to whether the target lesion meets a specified radiographic criterion. The stated threshold for partial response is a volume reduction of at least 20%, sustained for at least 4 weeks. Complete response, stable disease, and progressive disease are also defined in the registry. The title of the primary outcome refers to participants with a 20% or more change in target tumor volume, while the detailed definitions distinguish the direction and category of change. A count or percentage would describe how many participants met the endpoint definition; it would not, by itself, describe the average amount of volume change or the distribution of changes among participants.
General statistical explanation: a proportion is an estimate based on the observed participants, and a confidence interval describes the range of values reasonably compatible with the data under the chosen statistical method. Its width depends on the amount of information and the observed data. Neither a proportion nor a confidence interval for the primary response is reported in the registry record, so the endpoint's precision cannot be evaluated from the posted result information.
Why does the single-group design matter?
The trial is listed as single group, with allocation marked NA and masking listed as none. Thus, the primary endpoint is not a treatment-versus-control contrast. It is a description of outcomes among participants enrolled in the study. General statistical explanation: random allocation to a concurrent control group can support a comparison that accounts for differences in prognosis between groups, while a single-group design cannot make that randomized comparison. An observed change from baseline in one group is not itself an estimate of the difference that would have been observed under an alternative treatment.
Open-label conduct can also matter for assessment, particularly for outcomes involving judgment or participant reporting. The primary endpoint relies on volumetric MRI and response assessments by the NCI-POB, but masking is listed as none. The registry does not report further details about central review procedures, measurement reproducibility, or whether assessors were independent of treatment delivery. No conclusion about the practical influence of open-label assessment can be made from the listed design alone.
How should the repeated assessments be understood?
The protocol describes MRI response assessments after course 4, course 8, course 12, and after every 6 courses thereafter, with the primary timeframe extending from baseline to 24 months. This schedule implies repeated assessment of the target lesion during follow-up. General statistical explanation: repeated measurements can show the course of an outcome over time, but analyses must account for the fact that measurements from the same participant are related. The registry record does not report a longitudinal statistical model or explain how measurements across visits were combined for the primary result.
The treatment description also links continued therapy to tumor-volume thresholds after specified courses. Such rules define treatment decisions within the protocol, but do not tell the reader how many participants met those thresholds or continued treatment. Actual treatment exposure and discontinuation counts are not reported in the registry record. The stated endpoint timeframe and treatment rules should therefore not be mistaken for observed follow-up completeness.
What do the planning assumptions describe?
The registry's sample-size assumptions describe a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event planning, the illustration is defined in total events; other planning results are defined as participants per arm. These assumptions do not describe the trial's single-group design, which enrolled 19 participants and has no randomized comparator.
General statistical explanation: sample-size planning asks how much information a future comparison might need under specified assumptions. It is not a measure of the evidence observed in the completed trial and should not be interpreted as observed power. The registry's planning assumptions are not the same as the trial's own design justification. A sample-size justification for this study is not reported in the registry record. No numerical planning result is stated in the record information addressed here, and no planning figure can substitute for the missing primary outcome result.
What statistical details remain unavailable?
The registry reports 18 analyses, but the information described does not set out a complete statistical analysis plan. The primary endpoint's reported analysis method, handling of missing scans, uncertainty intervals, and any adjustment for multiple outcomes are not reported in the registry record. General statistical explanation: these details affect how a result is estimated and how uncertainty is interpreted. For example, different approaches to missing outcome data can make different assumptions about participants who lack an assessment. Without a stated approach, readers cannot assess the sensitivity of results to missingness.
Secondary outcomes involve different kinds of data, including toxicity, non-target lesion response, pharmacokinetic measures, and quality-of-life assessments. General statistical explanation: count outcomes, continuous measurements, and repeated assessments may require different summaries and models. The registry lists these outcome areas but does not report the methods or numerical results needed to evaluate their analyses. The primary finding should not be inferred from the number of planned analyses, from the detailed response rules, or from the stated study objective.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies a primary outcome and several secondary outcome areas, including evaluable participants treated, toxicity, response in up to 2 non-target PN, drug exposure measures, half-life, and quality of life. It also reports 18 analyses. The multiplicity strategy for interpreting results across these outcomes or analyses is not reported in the registry record. In general, when many outcomes or analyses are examined, the chance of finding an apparently notable result by chance can increase if results are interpreted without accounting for the number of comparisons. The record does not say whether an adjustment was planned or used, so no particular multiplicity approach should be assumed.
The primary-outcome population is described as all 19 participants enrolled, equivalent to intention to treat. That statement identifies the intended population but does not explain how participants without an evaluable MRI were treated in the analysis. The number with missing scans, reasons for missingness, any imputation method, and any sensitivity analyses are not reported in the registry record. General statistical explanation: missing data matter because participants without observed measurements may differ from those with measurements, and the analytic approach determines how that uncertainty is handled.
The registry describes assessment after specified treatment courses and through a 24-month timeframe, but does not report the number assessed at each time point or the completeness of follow-up. It also does not report whether the primary endpoint was analyzed using the last available scan, a defined visit, or another approach. These omissions limit evaluation of how well the endpoint population and observed measurements align. The registry's designation of the enrolled population should not be treated as proof that every participant contributed complete outcome data.
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 |
|---|---|---|---|
| Agent PD-0325901 | 2 | 19 | 10.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Agent PD-0325901 | 0 of 19 |
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 |
|---|---|
| Agent PD-0325901 | 19 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | Agent PD-0325901 |
|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | 1 of 19 |
| Back Pain | Musculoskeletal and connective tissue disorders | 1 of 19 |
| Pregnancy, puerperium and perinatal conditions, other | Pregnancy, puerperium and perinatal conditions | 1 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Agent PD-0325901 |
|---|---|---|
| Rash acneiform | Skin and subcutaneous tissue disorders | 18 of 19 |
| Nausea | Gastrointestinal disorders | 12 of 19 |
| Fatigue | General disorders | 11 of 19 |
| Headache | Nervous system disorders | 8 of 19 |
| Vomitting | Gastrointestinal disorders | 7 of 19 |
| Diarrhea | Gastrointestinal disorders | 6 of 19 |
| CPK Increased | Investigations | 6 of 19 |
| Dizziness | Nervous system disorders | 6 of 19 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 5 of 19 |
| Constipation | Gastrointestinal disorders | 4 of 19 |
Serious events with the highest arm-level rate: abdominal pain (5.3%), back pain (5.3%), pregnancy, puerperium and perinatal conditions, other (5.3%).
The registry reports 19 participants at risk for the serious adverse event summary, with 2 affected and 0 deaths. It lists Abdominal Pain, Back Pain, and Pregnancy, puerperium and perinatal conditions, other among the top serious-event terms, each reported as 5.3%. The record also reports 19 participants at risk and 19 affected for the other adverse-event summary. The two summaries have different classifications and should not be combined into one count.
These figures are safety descriptions, not a comparison with another group. The study is single group, and the registry does not provide a control-group rate. The listed event terms do not establish that an event was caused by PD-0325901. The registry information does not report event onset, duration, outcome, severity details beyond the serious classification, or investigator attribution. Nor does the listed frequency for each term show whether the same participant experienced more than one term. The serious-event summaries therefore provide a limited count-based account, rather than a complete evaluation of safety or comparative risk.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this phase 2 study was designed to assess radiographic response in a target PN among adolescents and adults with NF1 and growing or symptomatic, inoperable PN. It gives a target-volume response definition, a schedule of MRI assessments, protocol dosing details, and selected safety counts. Those details describe the intended measurement and the study's scope.
The record does not report the primary response count or percentage. It therefore does not establish how many participants experienced a 20% or more change in target tumor volume, how many had partial or complete response, or how many had stable or progressive disease. It also does not report a confidence interval or other uncertainty measure for the primary endpoint. The treatment objective and response criteria are not substitutes for observed results.
Even if the primary response result were available, the single-group design would support a description of outcomes among enrolled participants rather than a randomized comparison with an alternative. General statistical explanation: an observed within-group change is not the same estimand as a difference between treatment strategies. The design does not provide a concurrent control for separating treatment-associated change from other influences on tumor volume.
The endpoint is also limited to radiographic assessment of the target lesion. It does not directly summarize the response of all PN, pain, function, or quality of life. The registry lists some of these as secondary outcome areas, but their results are not reported in the registry record. Similarly, the safety counts identify reported events but do not establish causation or comparative safety.
Thus, the study record can be used to understand the planned population, intervention, measurement rules, and design limitations. It cannot support a conclusion about the magnitude or precision of the primary response, because that result is not reported. The same caution applies to the listed secondary outcomes: without their results and analysis details, they cannot be used to fill in the missing primary finding.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of how a radiographic endpoint can be defined in a single-group study. The protocol specifies volumetric MRI of a target lesion, response categories tied to sustained changes in volume, and assessment at named points during treatment. These details make the intended endpoint more operational than a general statement that tumors would be monitored.
The trial also illustrates why design and result reporting must be considered together. A single-group, open-label study can describe what happened among enrolled participants, but it cannot provide a randomized comparison against another treatment or no treatment. The objective of determining whether PD-0325901 results in objective responses is a research question; it is not itself a result. Here, the registry record does not report the primary response estimate, so readers cannot evaluate either its magnitude or its precision.
There is a further distinction between protocol rules and statistical evidence. The criteria for continuing treatment, the scan schedule, and the endpoint definitions explain how the study was organized. They do not show how many participants met a response threshold or how complete follow-up was. The registry's intention-to-treat population statement identifies the analysis population but does not provide missing-data details.
Finally, the registry includes safety and secondary outcome areas, but those outcomes require their own results and suitable interpretation. The serious adverse event counts cannot be compared with a control rate in this single-group study. Overall, the record highlights the value of transparent outcome reporting: without the primary estimate and uncertainty information, the clinical question remains statistically unresolved by 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 primary limitation for interpreting this trial record is that the primary outcome result is not reported in the registry record. The endpoint is defined, but no response count, percentage, confidence interval, or test result is stated. This prevents assessment of the observed response frequency and its precision.
The design is single group, open label, and has no comparator. The study can describe outcomes among participants receiving PD-0325901, but it cannot use randomization to compare those outcomes with an alternative. Since masking is listed as none, outcome assessment may also be susceptible to awareness of treatment; the registry does not describe assessor independence or measurement reproducibility in enough detail to evaluate that issue.
The enrolled population is 19 participants, and the registry identifies all enrolled participants as equivalent to the intention-to-treat population for the primary outcome. It does not report how many participants had evaluable MRI at each assessment, whether all enrolled participants contributed data, or how missing outcomes were handled. Actual treatment duration, adherence, and discontinuations are also not reported. These gaps make it difficult to assess follow-up completeness and the relationship between protocol-defined treatment rules and observed outcomes.
The primary measure concerns a target lesion, while the protocol also identifies non-target PN response, toxicity, pharmacokinetics, and quality of life as secondary areas. Their results and the methods used to analyze them are not reported in the registry record. The approach to multiplicity is also not reported, despite the registry identifying 18 analyses. The sample-size planning assumptions describe a two-arm illustration, whereas the completed study is single group; a study-specific sample-size justification is not reported. Together, these limitations restrict both outcome interpretation and assessment of the analysis plan.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: MEK Inhibitor PD-0325901 Trial in Adolescents and Adults With NF1 — NCT02096471.
- Registry record last updated 2019-01-10; status last verified 2018-12.
- Results first posted 2019-01-10.
- 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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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
This completed phase 2 study enrolled 19 adolescents and adults with NF1 and growing or symptomatic, inoperable PN. It evaluated oral PD-0325901 in an open-label, single-group design with no comparator. The primary endpoint was the percent of participants with a 20% or more change in target tumor volume, assessed by volumetric MRI from baseline to 24 months. The registry describes response categories and scan timing but does not report the primary response result.
The registry reports 2 participants with serious adverse events among 19 at risk, and 0 deaths. It lists three serious-event terms, each at 5.3%. Secondary outcomes include toxicity, non-target PN response, pharmacokinetics, and quality of life; their results are not reported in the registry record. Missing-data handling and multiplicity methods are also not reported. The single-group design supports descriptive interpretation only and does not provide a randomized treatment comparison.