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 Dose Escalation Pan-FGFR (Fibroblast Growth Factor Receptor) Inhibitor (Rogaratinib) (NCT01976741), a non-randomized phase 1 study. The primary outcome is Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01976741 |
| Phase | Phase 1 |
| Condition | Neoplasms |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 168 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Bayer |
| Results posted | Yes |
2. Clinical Question
The study asked whether rogaratinib could be administered to people with advanced solid tumors while investigators characterized its safety, tolerability, pharmacokinetics and maximum tolerated dose. It was the first study in which BAY1163877 was given to humans. The registry also describes dose-expansion groups selected by cancer type and FGFR expression profile, and assessments of tumor response and biomarkers. The primary outcome was a pharmacokinetic measure rather than a direct comparison of clinical benefit.
Population
Participants had refractory, locally advanced or metastatic solid tumors. The study began with participants with any type of solid tumor and later included all-comers and expansion groups for bladder cancer, squamous cell carcinoma of the head and neck, and squamous non-small cell lung cancer. The registry reports an enrollment of 168.
Intervention
Participants received oral rogaratinib, also identified as BAY1163877. The dose-escalation groups received oral solution or tablets at escalating doses. Expansion participants received oral tablets at 800 mg twice daily.
Comparator
There was no placebo group or randomized control group. The study was non-randomized, open-label and single-group in its overall model, so its arms do not constitute a like-for-like controlled comparison.
Primary question
What was the maximum plasma concentration, or Cmax, after a single dose of BAY1163877 on Cycle 1, Day -3, among participants with valid pharmacokinetic data? The registry describes the endpoint and measurement schedule, but its numerical Cmax results are not reported in the registry record.
3. Trial Design
This was a phase I, non-randomized, open-label, dose-escalation study sponsored by Bayer. The registry lists an enrollment of 168 and a completed status. The recorded start date is 2013-12-30, and the primary completion date is 2019-03-11. Participants and study personnel were not masked, and there was no placebo group.
The initial dose-escalation arm enrolled participants with solid tumors and used oral solution or tablet formulations. The actual dose-escalation cohorts were 100 mg (50 mg BID), 200 mg (100 mg BID), 400 mg (200 mg BID), 800 mg (400 mg BID), 1200 mg (600 mg BID), and 1600 mg (800 mg BID). The registry describes dose expansion after the maximum tolerated dose was defined. Expansion groups included all-comers and separate groups for bladder cancer, squamous cell carcinoma of the head and neck, and squamous non-small cell lung cancer. The expansion descriptions specify 800 mg orally twice daily for these groups.
The study assessed pharmacokinetics and also collected information on safety, tolerability, biomarker status, pharmacodynamic parameters and tumor response. The registry lists outcomes including response rate, progression-free survival, time to progression, duration of response and duration of treatment. The primary endpoint was Cmax after a single dose, not a randomized treatment-effect contrast.
The registry record does not report the allocation procedure within dose cohorts, a formal sample-size justification, or a detailed statistical analysis plan. Because treatment assignment was not randomized and masking was absent, observed differences across cohorts cannot be read as controlled estimates of treatment effects. Cohorts may differ in dose, formulation, cancer type and other characteristics.
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 988 participants were screened, of whom 168 participants were assigned into the study and received at least one dose of study medication.
Only the first 6 of 10 groups are shown.
Overall Study
| Stage | Rogaratinib 50 mg BID | Rogaratinib 100 mg BID | Rogaratinib 200 mg BID | Rogaratinib 400 mg BID | Rogaratinib 600 mg BID | Rogaratinib 800 mg BID |
|---|---|---|---|---|---|---|
| STARTED | 4 | 4 | 4 | 3 | 4 | 4 |
| COMPLETED | 3 | 4 | 1 | 2 | 4 | 4 |
| NOT COMPLETED | 1 | 0 | 3 | 1 | 0 | 0 |
Reasons for not completing this period:
| Reason | Rogaratinib 50 mg BID | Rogaratinib 100 mg BID | Rogaratinib 200 mg BID | Rogaratinib 400 mg BID | Rogaratinib 600 mg BID | Rogaratinib 800 mg BID |
|---|---|---|---|---|---|---|
| Withdrawal by Subject | 1 | 0 | 1 | 1 | 0 | 0 |
| Adverse Event | 0 | 0 | 2 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: MTD evaluation set: All participants of the total dose-escalation group who completed Cycle 1 or discontinued during Cycle 1 due to an adverse event or 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 11 groups are shown.
| Characteristic | Unit | Rogaratinib 50 mg BID | Rogaratinib 100 mg BID | Rogaratinib 200 mg BID | Rogaratinib 400 mg BID | Rogaratinib 600 mg BID | Rogaratinib 800 mg BID |
|---|---|---|---|---|---|---|---|
| Participants analysed | 4 | 4 | 4 | 3 | 4 | 4 | |
| Age, Continuous | Years | 52.5 (SD 20.4) | 58.5 (SD 12.4) | 55.8 (SD 15.3) | 56.3 (SD 9.8) | 56.8 (SD 12.9) | 64.3 (SD 8.4) |
| Sex: Female, Male: Female | Participants | 3 | 2 | 2 | 1 | 1 | 0 |
| Sex: Female, Male: Male | Participants | 1 | 2 | 2 | 2 | 3 | 4 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 4 | 4 | 4 | 3 | 4 | 4 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 1 | 1 | 1 | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 4 | 4 | 3 | 2 | 3 | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Eastern Cooperative Oncology Group (ECOG) Performance status: ECOG=0 | Participants | 2 | 1 | 1 | 1 | 2 | 2 |
| Eastern Cooperative Oncology Group (ECOG) Performance status: ECOG=1 | Participants | 2 | 3 | 3 | 2 | 1 | 1 |
| Eastern Cooperative Oncology Group (ECOG) Performance status: ECOG=2 | Participants | 0 | 0 | 0 | 0 | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Cmax (Maximum Drug Concentration in Plasma) of BAY1163877 After Single Dose Administration on Cycle 1, Day -3, measured over pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1).
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | µg/L |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was Cmax, the maximum concentration of BAY1163877 measured in plasma after a single dose on Cycle 1, Day -3. The measurement schedule included pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24 (Day -2) and 48 hour(s) post-dose (Day -1). The stated analysis population was participants with valid pharmacokinetic data on Cycle 1, Day -3; some expansion participants were included in the Rogaratinib expansion food effect.
The registry specified that Cmax would be reported as a geometric mean with a geometric coefficient of variation. In general, a pharmacokinetic endpoint describes drug exposure in the body, rather than directly measuring whether a tumor shrinks or how long a participant lives without progression. Cmax is used to characterize the peak concentration observed after dosing and can help describe exposure across dose levels or formulations. A geometric mean is used for measurements that are analyzed on a multiplicative scale, while a geometric coefficient of variation describes relative variability on that scale.
The registry record describes the endpoint but does not report its numerical result. Therefore, the actual peak concentration and its variability cannot be interpreted from the information reported for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study’s purpose and structure, but the primary endpoint results needed to describe measured Cmax are not reported in the registry record. Although the record specifies a geometric mean and geometric coefficient of variation, it does not provide the estimate or variability value. The endpoint’s timing and analysis population are described, but those details alone do not reveal the observed drug concentration.
The study was designed around dose escalation and expansion, not a randomized comparison against placebo or another treatment. Consequently, the record does not support a controlled estimate of how rogaratinib changed a clinical outcome relative to a comparator. The dose cohorts were not randomized, and the study was open-label. Any differences between groups could reflect dose, formulation, cancer type, participant characteristics or other differences, as well as treatment exposure.
The registry lists a range of secondary outcomes, including response rate as defined by RECIST Version 1.1, progression-free survival, time to progression, duration of response and duration of treatment. It also lists biomarker and pharmacodynamic assessments. However, numerical results for these outcomes are not included in the registry record reported for this study. The registry lists 42 outcome measures and 0 analyses. The available information therefore does not permit an interpretation of the magnitude or precision of clinical response, time-to-event outcomes or biomarker changes.
Safety counts are reported by dose-escalation and expansion group. The counts include participants with serious adverse events, participants with other adverse events and deaths. These are descriptive counts from groups that differ in size and clinical composition, not estimates from a randomized safety comparison. The counts alone do not establish that an event was caused by rogaratinib, and the death counts do not establish treatment attribution. The registry lists serious-event terms and percentages, but does not provide enough detail in this record to assess timing, event severity beyond the serious classification, exposure duration or attribution.
In general, a confidence interval communicates the range of effect estimates compatible with the data under the analysis assumptions. No confidence interval or statistical comparison for the primary endpoint is reported in the registry record. Without a reported estimate and its uncertainty, readers cannot judge precision. The record’s design can describe the conduct and intended assessments of this early-phase study, but the posted information does not show the numerical primary outcome or support a conclusion about comparative efficacy.
9. Statistical Methods Explained
The registry describes a phase I, open-label, non-randomized dose-escalation study, followed by dose-expansion groups. These features matter for interpreting the statistics. Dose escalation is used to examine exposure and tolerability across planned dose levels, while expansion cohorts can collect further information in selected participant groups. This design is not equivalent to a randomized trial: it does not assign comparable groups to different treatments by chance, and it does not provide a concurrent placebo group.
What does the primary endpoint measure?
Cmax is the maximum plasma concentration recorded after a dose. The planned sampling schedule spanned pre-dose through 48 hour(s) post-dose, with measurements at the stated time points. The endpoint is a pharmacokinetic description of drug concentration over time. It is different from outcomes such as tumor response or progression-free survival, which describe clinical or disease-course events.
The registry specifies geometric mean and geometric coefficient of variation. In general, geometric summaries are useful when measurements are positive and variation is more naturally considered on a multiplicative scale. A geometric coefficient of variation expresses variability relative to the geometric mean. These summaries do not, by themselves, show the range of individual participant values or the precision of the estimate. The registry record does not report the numerical Cmax estimate or its variability, so those quantities cannot be evaluated.
Why does the design limit comparisons?
With non-randomized allocation, participants in different dose or expansion groups may differ before treatment. Group membership also reflects different dose levels, formulations or cancer categories. A raw difference between groups would therefore mix treatment and group-composition differences. General statistical methods can adjust for measured characteristics, but adjustment cannot guarantee removal of unmeasured differences. The registry record does not report an adjusted analysis for the primary endpoint, and it lists 0 analyses.
Open-label conduct means treatment assignment was not masked. This is relevant to outcomes involving judgment, reporting or decisions about continued treatment. A pharmacokinetic laboratory measurement is less directly dependent on subjective judgment, but open-label conduct remains part of the study context and can affect other outcomes and care processes. No masking procedure is reported because the registry identifies masking as none.
What can event counts tell readers?
Safety data are presented as counts of participants at risk and counts affected, by group. A count gives the number of participants with at least one event meeting the reported category; it does not necessarily indicate the total number of individual event episodes. The record separates serious adverse events from other adverse events and also reports deaths. These categories should not be added together or interpreted as mutually exclusive unless the registry makes that explicit; such a relationship is not reported in the registry record.
In general, safety counts are descriptive. Their interpretation depends on the group denominator, length of exposure, how events were collected, and how seriousness and attribution were defined. The registry entries reported for this study do not provide all of those details. Comparing counts across groups is especially difficult when group sizes and participant populations differ and assignment is not randomized. The listed serious-event percentages are registry figures; no additional percentages or rates are calculated.
What is not available about the analysis?
The registry record does not report a detailed statistical analysis plan, a formal sample-size justification, or the methods used to handle missing pharmacokinetic measurements. It describes the analysis population for Cmax as participants with valid pharmacokinetic data on Cycle 1, Day -3, but does not report how many met that criterion or how validity was determined. It also does not report the handling of missing data for the secondary outcomes.
In general, an analysis population defines which participants contribute to a particular estimate. A complete-case pharmacokinetic analysis can be affected if participants without valid measurements differ from those with valid measurements. The available record does not allow readers to assess whether that concern arose or how it was addressed. Similarly, no interim-analysis procedures are reported. They should not be inferred from the phase or dose-escalation design.
Any sample-size planning illustration based on an observed effect is a hypothetical planning calculation, not observed power and not evidence that the study had a particular probability of detecting an effect. In general, power depends on the assumed effect, variability, design and analysis. The record does not document the study’s own sample-size justification, and its non-randomized structure does not supply a single controlled comparison on which to base a straightforward two-arm interpretation.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 42 outcome measures, covering pharmacokinetic, safety, tumor-response, time-to-event, biomarker and pharmacodynamic topics. It lists 0 analyses. The record does not report a hierarchy of endpoints, a multiplicity adjustment, or a prespecified strategy for controlling the chance of false-positive findings across multiple outcomes. Those procedures should not be inferred from the number or type of outcomes listed.
In general, multiplicity becomes relevant when several outcomes, time points, subgroups or statistical tests are examined. If many tests are interpreted without accounting for their number, the chance of at least one apparently notable result can increase. A prespecified primary endpoint can help organize interpretation, but it does not establish what correction or reporting strategy was used for other outcomes. Here the primary endpoint is identified as Cmax, while the numerical result is not reported in the registry record.
The record identifies the Cmax population as participants with valid pharmacokinetic data on Cycle 1, Day -3. It does not report the number included in that analysis, the amount or pattern of missing data, or the rules for excluding invalid measurements. Handling of missing information for the other outcomes is not reported in the registry record. Thus, readers cannot assess whether missingness could have influenced the reported outcome summaries.
The registry record also does not report a detailed statistical analysis plan, interim analyses, or a formal sample-size justification. The stated enrollment is 168, but enrollment alone does not explain how the study size was chosen or whether it was intended to support a particular precision or hypothesis test. General planning calculations should not be read as observed power or as evidence of the trial’s original design rationale.
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 |
|---|---|---|---|
| Rogaratinib Total Dose Escalation | 9 | 23 | 39.1% |
| Rogaratinib Dose Expansion (All Comers) | 14 | 23 | 60.9% |
| Rogaratinib Dose Expansion (BC) | 44 | 74 | 59.5% |
| Rogaratinib Dose Expansion (SCCHN) | 5 | 8 | 62.5% |
| Rogaratinib Dose Expansion (sqNSCLC) | 24 | 40 | 60.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Rogaratinib Total Dose Escalation | 3 of 23 |
| Rogaratinib Dose Expansion (All Comers) | 6 of 23 |
| Rogaratinib Dose Expansion (BC) | 17 of 74 |
| Rogaratinib Dose Expansion (SCCHN) | 2 of 8 |
| Rogaratinib Dose Expansion (sqNSCLC) | 12 of 40 |
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 |
|---|---|
| Rogaratinib Total Dose Escalation | 22 of 23 |
| Rogaratinib Dose Expansion (All Comers) | 23 of 23 |
| Rogaratinib Dose Expansion (BC) | 73 of 74 |
| Rogaratinib Dose Expansion (SCCHN) | 8 of 8 |
| Rogaratinib Dose Expansion (sqNSCLC) | 40 of 40 |
Most frequent serious adverse event terms
| Event term | Organ system | Rogaratinib Total Dose Escalation | Rogaratinib Dose Expansion (All Comers) | Rogaratinib Dose Expansion (BC) | Rogaratinib Dose Expansion (SCCHN) | Rogaratinib Dose Expansion (sqNSCLC) |
|---|---|---|---|---|---|---|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 3 of 23 | 1 of 23 | 1 of 74 | 0 of 8 | 5 of 40 |
| General physical health deterioration | General disorders | 0 of 23 | 0 of 23 | 5 of 74 | 1 of 8 | 1 of 40 |
| Pneumonia | Infections and infestations | 1 of 23 | 1 of 23 | 2 of 74 | 1 of 8 | 2 of 40 |
| Fatigue | General disorders | 1 of 23 | 1 of 23 | 2 of 74 | 0 of 8 | 1 of 40 |
| Urinary tract infection | Infections and infestations | 0 of 23 | 0 of 23 | 5 of 74 | 0 of 8 | 0 of 40 |
| Pyrexia | General disorders | 0 of 23 | 1 of 23 | 2 of 74 | 0 of 8 | 1 of 40 |
| Multiple organ dysfunction syndrome | General disorders | 0 of 23 | 2 of 23 | 2 of 74 | 0 of 8 | 0 of 40 |
| Hypercalcaemia | Metabolism and nutrition disorders | 1 of 23 | 2 of 23 | 1 of 74 | 0 of 8 | 0 of 40 |
| Acute kidney injury | Renal and urinary disorders | 0 of 23 | 0 of 23 | 2 of 74 | 0 of 8 | 2 of 40 |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | 0 of 23 | 1 of 23 | 0 of 74 | 1 of 8 | 2 of 40 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Rogaratinib Total Dose Escalation | Rogaratinib Dose Expansion (All Comers) | Rogaratinib Dose Expansion (BC) | Rogaratinib Dose Expansion (SCCHN) | Rogaratinib Dose Expansion (sqNSCLC) |
|---|---|---|---|---|---|---|
| Blood phosphorus increased | Investigations | 11 of 23 | 20 of 23 | 31 of 74 | 5 of 8 | 31 of 40 |
| Diarrhoea | Gastrointestinal disorders | 4 of 23 | 13 of 23 | 48 of 74 | 4 of 8 | 23 of 40 |
| Decreased appetite | Metabolism and nutrition disorders | 5 of 23 | 10 of 23 | 29 of 74 | 4 of 8 | 16 of 40 |
| Fatigue | General disorders | 7 of 23 | 7 of 23 | 28 of 74 | 2 of 8 | 11 of 40 |
| Nausea | Gastrointestinal disorders | 7 of 23 | 8 of 23 | 20 of 74 | 4 of 8 | 11 of 40 |
| Constipation | Gastrointestinal disorders | 2 of 23 | 10 of 23 | 25 of 74 | 3 of 8 | 7 of 40 |
| Anaemia | Blood and lymphatic system disorders | 2 of 23 | 4 of 23 | 17 of 74 | 3 of 8 | 12 of 40 |
| Dry mouth | Gastrointestinal disorders | 0 of 23 | 2 of 23 | 25 of 74 | 0 of 8 | 9 of 40 |
| Alopecia | Skin and subcutaneous tissue disorders | 1 of 23 | 6 of 23 | 20 of 74 | 0 of 8 | 8 of 40 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 2 of 23 | 5 of 23 | 17 of 74 | 1 of 8 | 5 of 40 |
Serious events with the highest arm-level rate: dyspnoea (13.0%), pain (12.5%), general physical health deterioration (12.5%), infection (12.5%), pneumonia (12.5%).
The registry reports serious adverse-event counts, other adverse-event counts and deaths separately for five groups. For Rogaratinib Total Dose Escalation, 9 of 23 participants were affected by serious adverse events, 22 of 23 by other adverse events, and 3 deaths were recorded. For Rogaratinib Dose Expansion (All Comers), the corresponding counts were 14 of 23, 23 of 23 and 6 deaths. For Rogaratinib Dose Expansion (BC), they were 44 of 74, 73 of 74 and 17 deaths. For Rogaratinib Dose Expansion (SCCHN), they were 5 of 8, 8 of 8 and 2 deaths. For Rogaratinib Dose Expansion (sqNSCLC), they were 24 of 40, 40 of 40 and 12 deaths.
The registry lists Dyspnoea at 13.0%, and Pain, General physical health deterioration, Infection, Pneumonia and Blood bilirubin increased each at 12.5%, among the top serious-event terms. These percentages are reproduced as recorded; the registry information does not specify their denominator or attribution details.
These are descriptive safety counts. They do not show whether events were judged related to treatment, how long participants were exposed, or whether an event occurred more than once in a participant. The death counts do not establish cause. Because the study was non-randomized, group counts should not be interpreted as comparative risks or as evidence that one group’s treatment was safer than another’s.
12. What the Result Does, and Does Not, Mean
The record describes an early-phase investigation of oral rogaratinib in people with advanced solid tumors. It establishes the study’s broad design, dose-escalation and expansion structure, the planned pharmacokinetic endpoint and the categories of safety and clinical outcomes collected. It also shows that the study was open-label and non-randomized, with no placebo group.
The primary endpoint is pharmacokinetic: maximum plasma concentration after a single dose on Cycle 1, Day -3. However, the numerical Cmax result and its geometric coefficient of variation are not reported in the registry record. Without those values, the posted information cannot describe the observed peak concentration, its variability or the precision of the estimate. The record also does not report numerical results for the listed secondary outcomes in the registry record for this analysis.
The safety figures describe the numbers of participants affected in each listed category and group. They are not a randomized comparison and should not be interpreted as evidence that differences among groups were caused by dose or cancer type. The record does not establish the cause of the reported deaths or whether the listed events were attributed to rogaratinib.
In general, a non-randomized dose-escalation study can provide descriptive information about exposure and tolerability across cohorts, but conclusions depend on complete outcome reporting and the analysis methods. The information in the registry record does not establish comparative clinical benefit, treatment efficacy, or a causal effect on tumor outcomes. It also does not permit an assessment of the uncertainty around the primary endpoint because its numerical estimate and interval are not reported. Interpretation should therefore remain limited to the study design, stated outcomes and descriptive safety counts actually recorded.
13. Why This Trial Matters Statistically
This trial is statistically important as a first-in-human, phase I study that combined dose escalation with expansion in selected tumor groups. Such studies involve questions about dose, formulation, pharmacokinetic exposure and tolerability before a controlled estimate of clinical effect is available. The study’s primary Cmax endpoint reflects that early pharmacology focus rather than a direct comparison of patient outcomes.
The design also illustrates why the structure of a trial shapes what its results can mean. Without randomization or a control group, comparisons among dose cohorts or cancer groups are descriptive and potentially confounded by differences in the participants and treatment context. The listed expansion groups are clinically distinct categories, so they should not be treated as interchangeable controls for one another.
The registry makes the distinction between endpoint definition and endpoint result especially important. It describes the Cmax measurement, units, summary statistic and sampling schedule, but the numerical estimate is not reported in the registry record. Similarly, it lists a broad set of secondary outcomes without the numerical findings in the registry record for interpretation. Listing an outcome demonstrates that it was specified for assessment; it does not, by itself, communicate the observed result or its precision.
The safety information is also an example of the limits of descriptive event counts. Counts can identify the recorded burden of events within study groups, but a causal safety comparison requires context about attribution, exposure and a suitable comparison design. The trial therefore demonstrates why readers should distinguish pharmacokinetic description, safety monitoring and controlled efficacy evaluation rather than treating them as interchangeable forms of evidence.
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 statistical interpretation is that the registry record does not report the numerical result for the primary Cmax endpoint. The record specifies the intended summary and analysis population but does not give the estimate, its variability, a confidence interval or the number of participants contributing valid data. The precision and distribution of the measured concentrations therefore cannot be assessed.
The design was non-randomized, open-label and without a placebo group. Dose escalation and expansion cohorts may differ in dose, formulation, cancer type and participant characteristics. These features limit direct comparison across groups and prevent interpretation of group differences as controlled treatment effects. The registry record does not report an adjusted comparison that would address these differences.
The record lists 42 outcome measures and 0 analyses. It does not report numerical findings for the listed clinical, biomarker and pharmacodynamic outcomes in the registry record. Nor does it report a detailed statistical analysis plan, multiplicity procedures, interim-analysis methods, missing-data rules or a formal sample-size justification. The analysis population for Cmax is described as participants with valid pharmacokinetic data on Cycle 1, Day -3, but the number and characteristics of those participants are not reported.
Safety counts are presented by group, but the registry entries do not detail exposure duration, event recurrence, seriousness criteria or attribution to study treatment. The record also reports deaths without establishing their causes. The percentages attached to serious-event terms do not have a denominator specified in the available information. These limitations mean that the reported counts can be described, but not converted into comparative risks or causal conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Dose Escalation Pan-FGFR (Fibroblast Growth Factor Receptor) Inhibitor (Rogaratinib) — NCT01976741.
- Registry record last updated 2021-05-06; status last verified 2021-04.
- Results first posted 2020-04-28.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes a completed, phase I, open-label, non-randomized study of rogaratinib (BAY1163877) in refractory, locally advanced or metastatic solid tumors. Bayer sponsored the study, which lists an enrollment of 168. The recorded dates are 2013-12-30 for study start and 2019-03-11 for primary completion.
The study used oral dose escalation followed by expansion groups, including all-comers and groups for bladder cancer, squamous cell carcinoma of the head and neck, and squamous non-small cell lung cancer. Its primary outcome was Cmax after a single dose on Cycle 1, Day -3, summarized as a geometric mean and geometric coefficient of variation. The numerical primary outcome is not reported in the registry record.
The registry lists 42 outcome measures and 0 analyses. It reports serious adverse-event counts, other adverse-event counts and deaths by group, along with selected serious-event terms. The design and reporting support descriptive interpretation, but not a randomized estimate of comparative treatment effect.