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 Infigratinib in Recurrent High-Grade Glioma Patients (NCT04424966), a na early/phase 1 study. The primary outcome is Total Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04424966 |
| Phase | EARLY/Phase 1 |
| Condition | Glioma, Glioblastoma, GBM |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 7 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Nader Sanai |
| Results posted | Yes |
2. Clinical Question
Population
Participants with recurrent high-grade glioma scheduled for surgical resection were the intended population. The brief summary describes eligibility involving an FGFR1 K656E or FGFR3 K650E mutation, or an FGFR3-TACC3 translocation. The listed conditions include glioma, glioblastoma and GBM. The registry record reports enrollment of 7.
Intervention
The intervention was infigratinib. The arm description specifies an oral Phase 0 regimen of 125 mg for 7 days before surgical resection. It also describes an expansion cohort regimen of 125 mg for 21 days of a 28-day treatment cycle; whether that cohort enrolled participants is not reported in the registry record.
Comparator
There was no separate comparator group. The study is listed as single-group, with no allocation and no masking. Tissue measurements from before and after treatment appear among the secondary outcomes, but the primary question is not a randomized comparison between treatments.
Primary question
The primary endpoint asks for the total concentration of infigratinib in gadolinium-enhancing and non-enhancing tumor tissue collected during surgery. The protocol description places collection approximately 8 hours after study drug administration. This is a pharmacokinetic question about drug concentration in tumor tissue, not a direct comparison of clinical outcomes.
In practical terms, the study was designed to measure whether infigratinib could be detected and quantified in different types of tumor tissue at the time of resection. Comparing enhancing with non-enhancing tissue distinguishes two tissue categories in the endpoint definition; the registry record does not describe a control group for that comparison. Secondary outcomes include changes in selected tissue markers and counts of adverse events, but numerical results for those outcomes are not reported in the registry record.
3. Trial Design
The registry describes an open-label, multicenter, single-group Phase 0 study of infigratinib in recurrent high-grade glioma participants scheduled for tumor resection. Phase 0 studies are generally early investigations that can characterize how a drug behaves in people, including whether it reaches a tissue of interest. That general description helps explain the focus on tumor concentration, but it does not establish what the results were in this trial.
The listed Phase 0 regimen was 125 mg of infigratinib orally for 7 days before resection. An expansion cohort is also described, with 125 mg administered orally for 21 days of a 28-day treatment cycle. The registry record does not report whether that expansion cohort proceeded, how many participants received either regimen, or whether every enrolled participant underwent resection.
The study started on 2020-07-21, had a primary completion date of 2023-01-31, and is listed as terminated. Enrollment is reported as 7, while the brief summary describes an intention to enroll up to 20 participants. The reason for termination and the relationship between the enrollment figure and the planned cohorts are not reported in the registry record.
With a single group and no allocation to a control arm, the design does not support a like-for-like treatment comparison. The open-label status means masking is listed as none; the record does not describe masking of laboratory personnel or other procedures. The named sponsor is Nader Sanai. A detailed protocol, including further operational design details, is not reported in the registry record.
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.
Phase 0
| Stage | Recurrent High Grade Glioma |
|---|---|
| STARTED | 7 |
| COMPLETED | 7 |
| NOT COMPLETED | 0 |
Expansion Phase
| Stage | Recurrent High Grade Glioma |
|---|---|
| STARTED | 3 |
| COMPLETED | 3 |
| NOT COMPLETED | 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 | Recurrent High Grade Glioma |
|---|---|---|
| Participants analysed | 7 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 |
| Age, Categorical: >=65 years | Participants | 3 |
| Age, Continuous | years | 63 (48 to 72) |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 4 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 5 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 7 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | Participants | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Total Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue, measured over Intraoperative.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Full Range |
| Unit | nM |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the total concentration of infigratinib in gadolinium-enhancing and non-enhancing tumor tissue. Tissue is described as being collected intraoperatively, approximately 8 hours after study drug administration, and analyzed using a validated liquid chromatography-mass spectrometry method. The endpoint is expressed in nM, with a geometric mean and full range specified as the summary measures.
Drug concentration in tumor tissue is used in early pharmacokinetic research to characterize drug exposure at a site relevant to the disease. Measuring enhancing and non-enhancing tissue separately can describe concentrations in both tissue categories named by the endpoint. It does not, by itself, establish that the drug reached a particular biological target, changed tumor behavior, or improved a clinical outcome. Those are distinct questions requiring relevant measurements and analyses.
A geometric mean is a way of summarizing positive measurements when values may vary multiplicatively rather than by equal additive amounts. It is commonly calculated by working on the logarithmic scale and transforming the summary back to the original scale. The full range describes the lowest and highest observed values; it is not a confidence interval and does not quantify the precision of the geometric mean.
The registry record does not report the geometric mean, the full range, or a confidence interval for this endpoint. It therefore does not permit a numerical assessment of the measured tissue concentrations or their precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive constraint is that the registry record identifies a primary pharmacokinetic endpoint but does not report its numerical result. The endpoint concerns total infigratinib concentration in enhancing and non-enhancing tumor tissue collected during surgery. Without the reported concentrations and their range, it is not possible to characterize the observed tissue exposure, its variability, or how precisely it was estimated. The record also does not report a confidence interval for the endpoint.
The design is single-group, open-label, and has no allocation to a comparator. Consequently, the primary endpoint is descriptive of measured drug concentration in the participants and tissue sampled; it is not a randomized estimate of a treatment effect. Even if a concentration result were available, a tissue concentration would answer a pharmacokinetic question. It would not by itself establish a change in tumor markers, clinical status, or survival. Those outcomes require their own reported measures and suitable interpretation.
The registry reports enrollment of 7 and describes a plan to enroll up to 20. The study is listed as terminated, but the reason for termination is not reported in the registry record. The enrollment count alone does not establish whether data collection was complete, whether all enrolled participants contributed to the primary endpoint, or whether the expansion cohort was conducted. Those details are also not reported. The posted record lists 22 outcome measures and no analysis records. The absence of analysis records means that a statistical analysis result is not available in the registry record; it should not be interpreted as evidence that no analyses were performed outside the record.
Safety figures require similarly careful reading. Among the 7 participants in the adverse-event group, 0 are listed with serious adverse events, 5 with other adverse events, and 6 deaths are reported. The record does not specify the cause or timing of the deaths, nor does it state whether they were considered related to treatment. These counts cannot be combined into a causal conclusion, and the death count should not be treated as an adverse-event attribution.
Overall, the registry record describes the study question and selected design features, but provides limited information for judging estimates, uncertainty, or clinical relevance. It does not report the reason for termination, analysis populations, handling of missing observations, multiplicity procedures, or detailed statistical methods. Any interpretation beyond the recorded design and counts would require information not reported in the registry record.
9. Statistical Methods Explained
The study’s principal statistical question is a pharmacokinetic one: what total concentration of infigratinib was measured in two specified categories of tumor tissue at surgery? The endpoint names enhancing and non-enhancing tissue, gives nM as the unit, and specifies a geometric mean with full range. These choices describe the intended summary of concentration measurements rather than a comparison of clinical outcomes between treatment groups.
Why use a geometric mean?
As a general statistical concept, a geometric mean is useful for positive measurements that may vary multiplicatively. For example, a value that is a multiple of another can be more naturally described on a logarithmic scale than as an additive difference. The geometric mean is calculated from log-transformed observations and then expressed back on the original measurement scale. This can give a representative center when data are right-skewed, although it does not remove the need to inspect the observed values or describe their spread.
The registry record specifies the geometric mean but does not report a value for it. It also does not report the number of tissue samples contributing to each tissue category, the distribution of measurements, or a confidence interval. Without those results, the central concentration and its estimation precision cannot be assessed from the registry record.
What does the full range describe?
In general, a full range gives the minimum and maximum observed values. It communicates the span of the observations, including extreme values, but says little on its own about how observations are distributed between those extremes. It is not a measure of inferential precision. A confidence interval, by contrast, is an interval estimate for a parameter and conveys uncertainty under the analysis assumptions. No confidence interval is reported for the primary endpoint in the registry record.
Concentration results can vary across participants and tissue samples. As a general matter, the range and a measure of central tendency answer different questions: the center describes a typical level under the chosen summary, while the range shows the observed extremes. Neither summary can reveal whether differences arose from biological variation, sample handling, assay variation, or other sources without additional information and analysis.
How should the tissue categories be understood?
The primary endpoint names gadolinium-enhancing and gadolinium non-enhancing tumor tissue, and specifies intraoperative collection approximately 8 hours after study drug administration. Those categories define where the concentration is to be measured. A comparison between tissue categories, if reported, would describe concentrations across those categories; it would not be a randomized treatment comparison. The registry record does not report a numerical contrast between the tissue categories or an analysis method for such a contrast.
The described assay is a validated liquid chromatography-mass spectrometry method. In general, an analytical assay is used to quantify a compound in a collected specimen. Calling a method validated describes the assay in the endpoint description, but the registry record does not provide assay-performance characteristics, such as precision, lower limit of quantification, or handling of values below a detection threshold. Those details should not be inferred.
What can be inferred from the design?
A single-group study can describe measurements among the participants who contribute data. It does not, without a comparator, estimate how those measurements would differ under another treatment or no treatment. The lack of allocation and masking is consistent with the registry’s description of an open-label, single-group study. The primary question remains the concentration measurement, not a treatment-effect estimate against a control arm.
The registry record lists 22 outcome measures and no analysis records. It does not report a statistical analysis plan, model specifications, covariate adjustments, confidence-interval methods, or analysis populations. It is therefore not possible to identify which inferential procedures, if any, were used for the outcome measures from the registry record. A general explanation of statistical methods cannot substitute for a trial-specific analysis description.
How do sample-size illustrations differ from trial planning?
As a general concept, a power calculation estimates the sample size needed under stated assumptions to detect a specified effect with a chosen probability, subject to the statistical model and design. Such calculations are planning illustrations, not results from participants and not evidence that a study had a particular probability of detecting an effect after it was completed. The record describes an illustration framework using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a stated fraction of an observed effect. Time-to-event illustrations use a total event count; other illustrations are expressed as participants per arm.
That framework does not establish that this single-group study was designed as a two-arm comparison. Nor does it establish that the registry’s own sample-size justification used those assumptions. The study’s sample-size justification is not reported in the registry record. The observed effect needed to ground such illustrations is not reported for the primary endpoint in the registry record, and no resulting planning sample-size values are reported in the record. Planning quantities should be read as hypothetical design illustrations, not as observed sample sizes or observed power.
Because the study has no recorded analysis results, the statistical interpretation is mainly about what the endpoint and design could address. The endpoint could characterize tumor tissue concentration if the measurements and their summaries were reported. It cannot, on its own, answer questions about clinical benefit, causal effects, or precision when the numerical results and analysis details are absent.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 22 outcome measures, including tissue-marker changes and adverse-event outcomes, in addition to the primary concentration endpoint. When a study evaluates multiple outcomes, the chance of at least one apparently notable finding can increase if each is tested separately. As a general statistical approach, investigators may prespecify a primary outcome, organize secondary outcomes, or use an adjustment procedure. The registry record does not report whether any multiplicity strategy was specified or applied.
No analysis records are listed. The registry record does not report how missing measurements were handled, whether data were imputed, or whether analyses used all enrolled participants or a defined subset. It also does not identify analysis populations for the primary or secondary outcomes. These omissions prevent assessment of whether participants with unavailable tissue, incomplete dosing, or other missing measurements were included in any analysis; none of those situations should be assumed to have occurred.
The distinction between an outcome being listed and an outcome having a reported analysis is important. Listing an outcome describes what the study planned to measure; it does not establish that the measurement was obtained, analyzed, or reported. The registry record does not provide a detailed statistical plan, an account of deviations from such a plan, or an explanation for the absence of analysis records.
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 |
|---|---|---|---|
| Recurrent High Grade Glioma | 0 | 7 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Recurrent High Grade Glioma | 6 of 7 |
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 |
|---|---|
| Recurrent High Grade Glioma | 5 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Recurrent High Grade Glioma |
|---|---|---|
| Nausea | Gastrointestinal disorders | 3 of 7 |
| Fatigue | General disorders | 3 of 7 |
| Diarrhea | Gastrointestinal disorders | 2 of 7 |
| Constipation | Gastrointestinal disorders | 2 of 7 |
| Headache | Nervous system disorders | 2 of 7 |
| Depression | Psychiatric disorders | 2 of 7 |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | 1 of 7 |
| Dyspepsia | Gastrointestinal disorders | 1 of 7 |
| Aphthous ulcer | Gastrointestinal disorders | 1 of 7 |
| Abdominal pain | Gastrointestinal disorders | 1 of 7 |
The adverse-event record lists a group titled recurrent high-grade glioma with 7 participants at risk. Within that group, 0 participants are recorded with serious adverse events, 5 with other adverse events, and 6 deaths. These are distinct reported counts and should be kept distinct when interpreting safety.
A count of 0 serious adverse events in the listed group means that none are recorded in that category for the group. It does not establish that no adverse events of any kind occurred: 5 participants are listed with other adverse events. The record also lists deaths, but does not specify their timing, causes, or relationship to study treatment. The death count is not a measure of treatment-related deaths unless the record explicitly identifies such attribution, which it does not.
The registry record does not report the specific serious adverse-event terms; no top serious terms are listed. It also does not provide event-level descriptions, exposure-adjusted rates, or follow-up details that would help contextualize the counts. Because the group is small, the counts are descriptive and should not be treated as precise estimates of safety in a broader population. No causal conclusion about infigratinib can be drawn from these counts alone.
12. What the Result Does, and Does Not, Mean
The registry record describes an early, single-group study intended to measure infigratinib concentration in enhancing and non-enhancing recurrent high-grade glioma tissue collected at surgery. It also identifies secondary outcomes involving tissue markers and adverse events. These features define the questions the study was set up to address, but the record does not report numerical results for the primary concentration endpoint or the secondary tissue-marker outcomes.
Accordingly, the record does not establish how much infigratinib was measured in tumor tissue, how variable those measurements were, or how precise the estimates were. It also does not establish whether the concentrations differed between the two tissue categories. The endpoint is pharmacokinetic: a concentration measurement can describe drug exposure in sampled tissue. It is not, by itself, evidence of biological activity or a clinical outcome.
Because there was no comparator group, the design cannot provide a randomized estimate of what would have happened under another treatment or no treatment. The absence of a control does not make a descriptive concentration measurement meaningless, but it limits the kinds of comparative conclusions the study can support. No treatment-effect conclusion should be drawn from the design description or safety counts alone.
The record reports enrollment of 7, describes a plan to enroll up to 20, and lists the trial as terminated. It does not report why the trial ended, whether the planned expansion cohort proceeded, or how many participants contributed to each endpoint. The recorded safety counts are descriptive; the relation of deaths to treatment is not reported. The registry record therefore supports a limited account of study design and recorded counts, not a complete evaluation of efficacy, pharmacokinetics, or safety.
13. Why This Trial Matters Statistically
This trial is statistically interesting because its primary question is about drug concentration in human tumor tissue rather than a conventional comparison of clinical outcomes. Measuring a compound in tissue collected during surgery can address a pharmacokinetic question that is difficult to answer from outcomes alone: whether and at what concentration the compound is present in the sampled tissue. The separate enhancing and non-enhancing tissue categories make the intended measurement more specific.
The study also illustrates the limits of interpreting an early, single-group design. A descriptive concentration endpoint can characterize observations in the participants studied, but it does not create a control comparison. Concentration, biological response, and clinical outcome are different kinds of evidence. Keeping those distinctions clear prevents an early pharmacokinetic measure from being mistaken for proof of a clinical effect.
Registry completeness matters for statistical interpretation. Here, the record reports enrollment and design features, but does not report primary endpoint values, analysis records, or the reason for termination. Without the endpoint estimates, their variability and precision cannot be assessed. Without analysis details, it is not possible to determine how missing data, analysis populations, or multiple outcomes were handled.
The listed safety counts also demonstrate why categories and attribution matter. Serious adverse events, other adverse events, and deaths are reported separately, and the record does not establish a causal relationship between deaths and treatment. Those counts should be read as descriptive registry entries rather than as a comparative safety estimate.
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 for interpreting the posted record is the absence of numerical primary endpoint results. Although the endpoint and its intended summary are described, the geometric mean and full range are not reported. The record also does not provide a confidence interval, the number of tissue samples contributing to each category, or a numerical comparison between enhancing and non-enhancing tissue.
Enrollment is reported as 7, while the brief summary describes an intention to enroll up to 20. The study is listed as terminated, but the reason is not reported. The record does not explain whether participants entered the Phase 0 cohort, the expansion cohort, or both, nor does it report how many participants received each regimen or contributed specimens. The expansion cohort is described in the arm information, but its conduct is not confirmed.
The registry record does not report the analysis populations, missing-data procedures, statistical analysis plan, multiplicity procedures, or detailed assay-performance characteristics. It also does not report the cause or timing of deaths or their relationship to treatment. These gaps limit interpretation of the concentration endpoint and safety counts. Because the study has no comparator group, it cannot provide a randomized treatment comparison. These limitations concern what can be concluded from the registry record; they do not establish what analyses or procedures may have occurred outside it.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Infigratinib in Recurrent High-Grade Glioma Patients — NCT04424966.
- Registry record last updated 2025-10-24; status last verified 2025-09.
- Results first posted 2025-10-24.
- 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
NCT04424966 is listed as a terminated, open-label, multicenter, single-group Phase 0 study of infigratinib in recurrent high-grade glioma participants scheduled for resection. The registry reports enrollment of 7 and a primary completion date of 2023-01-31. The brief summary describes a plan to enroll up to 20 participants.
The primary endpoint is total infigratinib concentration in enhancing and non-enhancing tumor tissue collected intraoperatively, approximately 8 hours after study drug administration. It specifies nM, a geometric mean, and a full range. Numerical primary endpoint results and analysis records are not reported in the registry record. The record lists 22 outcome measures and includes adverse-event counts, but does not report the reason for termination, the analysis populations, or detailed statistical methods.