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 Copanlisib (BAY 80-6946) in Combination With Gemcitabine and Cisplatin in Advanced Cholangiocarcinoma (NCT02631590), a na phase 2 study. The primary outcome is Progression Free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02631590 |
| Phase | Phase 2 |
| Condition | Biliary Carcinoma, Gall Bladder Carcinoma, Cholangiocarcinoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | n/a |
| Lead sponsor | H. Lee Moffitt Cancer Center and Research Institute |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns adults with advanced cholangiocarcinoma, according to its brief summary and title. The registry record also lists biliary carcinoma, gall bladder carcinoma, cholangiocarcinoma, and gastrointestinal tumor among the conditions. It records enrollment of 24, but eligibility criteria and participant characteristics are not reported in the registry record.
Intervention
The registered combination is copanlisib with gemcitabine and cisplatin. The treatment plan specifies cisplatin (25 mg/m²), gemcitabine (1000 mg/m²), and copanlisib (60 mg) on days 1 and 8, with day 15 off, on an every 21-days schedule. The record does not describe how many participants received each planned dose or how long they received treatment.
Comparator
There is no separate comparison group in this single-group study. Allocation is listed as NA and masking as none. Results therefore describe participants in the combination group; they do not provide a randomized comparison with another treatment or a control group.
Primary question
The primary outcome is progression-free survival (PFS), with a six-month timeframe and a registered measure of median PFS with a 95% confidence interval. The outcome description defines PFS from study entry until documented progression, death from any cause, or last follow-up, whichever occurs first. The numerical PFS result is not reported in the registry record, so the clinical question cannot be answered from the posted outcome results.
3. Trial Design
This is a phase II, single-group study registered as completed. Its title identifies the treatment as copanlisib (BAY 80-6946) in combination with gemcitabine and cisplatin for advanced cholangiocarcinoma. The registry record lists enrollment of 24. That enrollment figure does not establish how many participants were included in each outcome analysis, and the analysis population is not reported in the registry record.
The treatment plan describes cisplatin at 25 mg/m², gemcitabine at 1000 mg/m², and copanlisib at 60 mg on days 1 and 8, with day 15 off, on an every 21-days schedule. The record lists all three medicines as drug interventions. It does not report treatment modifications, adherence, or the duration of treatment received by participants.
Allocation is listed as NA, masking as none, and the model as single group. There is therefore no randomized, masked, parallel-arm comparison in the registered design. The posted outcomes should be read as descriptions of this treatment group, not as evidence of a difference relative to a control group. The record does not report a protocol-defined comparator.
The study start date is 2016-07-05, the primary completion date is 2019-10-25, and the status is completed. The primary outcome is PFS, described with a six-month timeframe. Response rate and overall survival are listed as secondary outcomes. The registry record does not report a detailed statistical analysis plan, sample-size justification, or interim-analysis plan. Those omissions limit what can be concluded about how the study was intended to estimate or test its 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.
Overall Study
| Stage | Combination Therapy |
|---|---|
| STARTED | 24 |
| COMPLETED | 24 |
| 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.
Population: All participants that received at least one dose of study drug
| Characteristic | Unit | Combination Therapy |
|---|---|---|
| Participants analysed | 24 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 12 |
| Age, Categorical: >=65 years | Participants | 12 |
| Sex: Female, Male: Female | Participants | 15 |
| Sex: Female, Male: Male | Participants | 9 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 3 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 21 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| 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 | 22 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | participants | 24 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival (PFS), measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival measures the time from study entry until a participant has documented disease progression or dies, whichever happens first. For this study, the registry outcome description also identifies the date of last follow-up as an endpoint for the calculation. The registered primary outcome has a six-month timeframe and specifies median PFS with a 95% confidence interval, but its numerical estimate is not reported in the registry record.
The outcome description says response and progression are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1. It defines progressive disease as at least a 20% increase in the sum of target-lesion diameters, using the smallest on-study sum as the reference, with an absolute increase of at least 5 mm. The appearance of one or more new lesions also counts as progression.
As a general statistical concept, PFS combines information about progression and death into a time-to-event outcome. It can describe how long participants remain without either event, while accounting for follow-up time. The median is the point at which half of the estimated event-time distribution lies on either side, when it can be estimated. A confidence interval conveys uncertainty around an estimate; its numerical limits are needed to judge precision. Neither a median PFS value nor its interval is reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record identifies median PFS as the primary outcome and describes a six-month timeframe. However, it does not report a numerical PFS estimate or its 95% confidence interval. As a result, the primary outcome cannot be interpreted quantitatively from the posted results. The absence of a numerical estimate is not evidence that PFS was favorable or unfavorable; it means the registry record does not provide the result needed to assess its size or precision.
The record lists response rate and overall survival as secondary outcomes, but their numerical results are not reported in the registry record. It lists three outcome measures and no analyses. Without endpoint estimates, event counts for PFS, or analysis details, readers cannot determine how outcomes were calculated, how many participants contributed to them, or how uncertain any estimated treatment-group outcomes would be.
The study has a single treatment group, with no randomized comparator. Therefore, even if an outcome estimate were available, it would describe the observed experience in that group. It could not by itself establish how that experience differs from a control or from another treatment. General statistical interpretation of a treatment effect requires a comparison that supports a difference estimate and its uncertainty; this design does not provide a randomized treatment contrast.
The safety record does contain group-level figures. It lists 12 participants at risk for serious adverse events and 12 affected, with 24 at risk for other adverse events and 24 affected; deaths are listed as 18. These figures should be read as registry entries for the combination group, not as comparative evidence. The record does not explain the relationship between the listed deaths and the PFS endpoint, nor does it give enough detail to infer causes or treatment attribution.
Several serious adverse-event terms are listed with percentages, including abdominal pain, ascites, sepsis, and increased blood bilirubin, each at 8.3%, and anemia and colitis, each at 4.2%. The record does not provide the definitions, event-level counts, or attribution details needed to interpret these percentages beyond their appearance as listed serious-event terms. They do not supply the missing primary PFS estimate.
Overall, the posted record gives the study design, treatment schedule, primary-outcome definition, and some safety summaries, but not the numerical efficacy outcomes. Any conclusion about the magnitude or precision of PFS, response rate, or overall survival would go beyond what is reported in the registry record.
9. Statistical Methods Explained
What does a time-to-event outcome describe?
As a general statistical concept, a time-to-event outcome records the time until a defined event occurs. For this study, the registered event definition for PFS includes documented disease progression or death from any cause, and the outcome description identifies last follow-up as the other endpoint in the calculation. Participants can have different lengths of follow-up, so a time-to-event analysis is designed to use information about both whether an event occurred and how long a participant was followed.
The registry record names median PFS as the primary measure. A median is a summary of the event-time distribution rather than a comparison of two treatments. To interpret it, readers need the estimate and its uncertainty. Although the record specifies a 95% confidence interval, it does not report the median or interval limits. The timeframe is listed as six months, while the measure is specified as median PFS; the numerical result and further explanation of that timeframe are not reported in the registry record.
What does a confidence interval contribute?
As a general statistical concept, a confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis. It is not a guarantee that the true value lies within the reported limits, and it does not on its own indicate whether an outcome is clinically important. A narrower interval generally conveys greater precision than a wider one, but the estimate and the interval must be available to make that assessment. Here, the interval is named in the outcome definition, but its bounds are not reported in the registry record.
How does progression get defined?
The registered description says progression is assessed using revised RECIST guidelines, version 1.1. It defines progression as at least a 20% increase in the sum of target-lesion diameters relative to the smallest sum on study, together with an absolute increase of at least 5 mm. The appearance of one or more new lesions also qualifies as progression. These criteria make the outcome definition more explicit than a general statement that disease worsened. The registry record does not report further details about assessment timing, independent review, or how disagreements in assessments were handled.
What does a single-group design allow?
The study is registered as single group, with allocation listed as NA and masking as none. In general, a single-group study can describe outcomes among people who receive a treatment plan. It does not provide a randomized control group for estimating a comparative treatment effect. Outcomes may also reflect factors other than the intervention, and a single-group result cannot separate those influences in the way a randomized comparison is designed to do.
The registry record lists enrollment of 24. Enrollment does not necessarily equal the number included in every endpoint analysis. The number analyzed for PFS, the number excluded from any analysis, and the reasons for exclusions are not reported in the registry record. Without these details, readers cannot assess whether the analysis population matches the enrolled group or how follow-up availability may affect the result.
What information about the analysis is missing?
The registry record lists no analyses. It does not report a detailed statistical analysis plan, a specific estimator for PFS, a censoring rule beyond the endpoint description's reference to last follow-up, or methods for calculating the confidence interval. In general, censoring occurs when an event time is not observed during available follow-up; appropriate handling matters because a participant with no recorded event is not necessarily known to remain event-free indefinitely. The exact approach used in this study is not reported in the registry record.
The record also does not report a hazard ratio or a comparative analysis. General methods for time-to-event comparisons can estimate relative event rates between groups, but such an estimate requires a comparison and method details. The study's registered design has no separate comparison group, and no hazard-ratio result is reported. It would be inappropriate to infer a comparative effect from the group-level information.
As a general statistical concept, over-dispersion matters when observed variability exceeds what a model assumes; accounting for it can affect uncertainty estimates and tests. The registry record does not describe a count model or an over-dispersion assessment, so this issue cannot be tied to a reported analysis in this study. More broadly, without methods and outcome estimates, readers cannot independently evaluate model assumptions, precision, or robustness.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists three outcome measures: PFS as the primary outcome, with response rate and overall survival as secondary outcomes. When a study evaluates multiple outcomes, a statistical plan may specify which result is primary and how the interpretation of additional tests will account for the number of questions considered. This is a general concern because examining multiple results can increase the chance of finding an apparently notable result by chance. The record does not report a multiplicity strategy, such as an adjustment, hierarchy, or other prespecified approach.
The record lists no analyses and does not report numerical results for PFS, response rate, or overall survival. It also does not provide p-values or a detailed analysis plan. Consequently, there is no basis in the registry record for assessing how multiplicity was handled in the reported findings, or whether a particular endpoint result was selected after examining other outcomes.
Missing-data information is also limited. The record does not describe the amount or pattern of missing outcome data, reasons for missingness, or any imputation method. As a general statistical concept, missing outcomes can affect estimates when participants with unavailable follow-up differ from those whose outcomes are observed. The registered PFS definition includes last follow-up in its time calculation, but this does not by itself explain how all incomplete follow-up was handled.
The analysis populations are not reported in the registry record. It is not stated how many participants were included in each outcome analysis, whether any participants were excluded, or how deaths and withdrawals were handled for outcomes other than PFS. These omissions prevent assessment of the relationship between the enrollment of 24 and the analyzed populations.
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 |
|---|---|---|---|
| Combination Therapy | 12 | 24 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Combination Therapy | 18 of 24 |
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 |
|---|---|
| Combination Therapy | 24 of 24 |
Most frequent serious adverse event terms
| Event term | Organ system | Combination Therapy |
|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | 2 of 24 |
| Ascites | Gastrointestinal disorders | 2 of 24 |
| Sepsis | Infections and infestations | 2 of 24 |
| Blood bilirubin increased | Investigations | 2 of 24 |
| Anemia | Blood and lymphatic system disorders | 1 of 24 |
| Colitis | Gastrointestinal disorders | 1 of 24 |
| Colonic obstruction | Gastrointestinal disorders | 1 of 24 |
| Dysphagia | Gastrointestinal disorders | 1 of 24 |
| Gastrointestinal disorders -Other | Gastrointestinal disorders | 1 of 24 |
| Nausea | Gastrointestinal disorders | 1 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Combination Therapy |
|---|---|---|
| Lymphocyte count decreased | Investigations | 18 of 24 |
| Platelet count decreased | Investigations | 18 of 24 |
| Fatigue | General disorders | 17 of 24 |
| White blood cell decreased | Investigations | 17 of 24 |
| Neutrophil count decreased | Investigations | 16 of 24 |
| Anemia | Blood and lymphatic system disorders | 16 of 24 |
| Hypertension | Vascular disorders | 15 of 24 |
| Hyperglycemia | Metabolism and nutrition disorders | 13 of 24 |
| Nausea | Gastrointestinal disorders | 12 of 24 |
| Diarrhea | Gastrointestinal disorders | 11 of 24 |
Serious events with the highest arm-level rate: abdominal pain (8.3%), ascites (8.3%), sepsis (8.3%), blood bilirubin increased (8.3%), anemia (4.2%).
The registry record lists one combination-therapy group, with 24 participants at risk for other adverse events and 24 affected. For serious adverse events, it lists 24 at risk and 12 affected. Deaths are listed as 18. These are separate registry entries; the record does not explain whether deaths were counted within any adverse-event category or provide their causes.
The serious adverse-event terms listed with percentages are abdominal pain, ascites, sepsis, and increased blood bilirubin, each at 8.3%, plus anemia and colitis, each at 4.2%. These percentages should be treated as the registry's reported values. The record does not provide additional context on event duration, severity grading, timing, repeat events, or whether an event was judged related to a study drug.
As a general statistical concept, adverse-event summaries describe observed events in the monitored group. Without a comparator and further attribution detail, they do not establish that the treatment caused an event or indicate how event frequency compares with another treatment. The figures also do not replace the missing numerical results for the primary PFS outcome.
12. What the Result Does, and Does Not, Mean
The record describes a phase II investigation of copanlisib combined with gemcitabine and cisplatin in advanced cholangiocarcinoma. It provides a single-group design, a treatment schedule, a primary PFS definition, and selected safety entries. It does not report the numerical primary outcome or the listed secondary outcome results. The central outcome question therefore remains unanswered by the posted results.
Even if the registry record had reported a PFS estimate, a result from this single-group study would describe outcomes among participants in that group. There is no randomized comparator from which to estimate a treatment difference. As a general statistical principle, a group outcome alone cannot establish what would have happened to comparable participants under a different treatment or control condition.
The absence of numerical PFS, response-rate, and overall-survival results also means that the size and precision of any observed outcomes cannot be evaluated. The registry record names a 95% confidence interval for median PFS, but does not give the estimate or interval limits. The safety entries provide some counts and listed event terms, but they do not establish attribution, comparative safety, or the reasons for the listed deaths.
These limits are about what the registry record reports, rather than proof that an analysis was never conducted or that an outcome was absent. The record's completed status and its planned outcome definitions do not supply the missing numerical results. Conclusions should therefore remain confined to the study design, registered measures, and safety summaries that are actually recorded.
13. Why This Trial Matters Statistically
This study raises an important statistical distinction between describing outcomes and estimating a comparative treatment effect. Its single-group design can characterize a treatment cohort, but it does not create a randomized contrast. That distinction matters when readers encounter an outcome label such as PFS: the endpoint may be clinically and statistically useful, but the design determines what inferences a result can support.
The primary outcome is time-to-event, with progression and death included in its definition. This kind of endpoint requires attention to follow-up and event ascertainment, not just a final event count. The registry record specifies a median and confidence interval but does not report their numerical values or analysis details. Thus, the endpoint's statistical structure is clear at a broad level, while the actual estimate and its precision cannot be assessed from the record.
The study also lists response rate and overall survival, illustrating why prespecified outcome priorities and multiplicity methods matter in clinical research. The registry record does not describe how results across these outcomes were to be interpreted together. Its safety entries add a separate descriptive dimension, but cannot fill the gap in efficacy outcome reporting or create a comparison group.
For biostatisticians and clinical researchers, the record underscores the value of transparent outcome reporting: numerical estimates, uncertainty intervals, analysis populations, missing-data handling, and analysis methods are all needed to judge the strength and limits of evidence. Without them, readers can understand the registered question and design, but cannot evaluate the magnitude or precision of the primary outcome.
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.
A key limitation for interpreting this specific record is that the numerical PFS result is not reported, despite PFS being the primary outcome. Its 95% confidence interval is named but not numerically presented. The record also lists response rate and overall survival as secondary outcomes without numerical results. Therefore, outcome magnitude and precision cannot be evaluated from the registry record.
The study is single group, with allocation listed as NA and no masking. There is no randomized comparator, so the record cannot support a randomized between-group treatment comparison. Enrollment is listed as 24, but the number of participants contributing to each outcome analysis and the analysis populations are not reported. Participant characteristics and detailed eligibility criteria are also not reported in the registry record.
The outcome description gives a progression definition based on revised RECIST guidelines, version 1.1, including a 20% relative increase and an absolute increase of at least 5 mm, or new lesions. However, details about assessment timing, review procedures, and handling of incomplete assessments are not reported. The registry record does not explain its statistical methods, missing-data procedures, multiplicity strategy, or sample-size justification.
Safety reporting is limited to group-level counts and selected serious-event terms with percentages. Attribution, timing, severity grading details, and causes of deaths are not reported. These limits do not establish that relevant information does not exist elsewhere; they define what can be interpreted from the registry record itself.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Copanlisib (BAY 80-6946) in Combination With Gemcitabine and Cisplatin in Advanced Cholangiocarcinoma — NCT02631590.
- Registry record last updated 2021-08-04; status last verified 2021-08.
- Results first posted 2020-11-02.
- 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
NCT02631590 is a completed phase II, single-group study of copanlisib with gemcitabine and cisplatin in advanced cholangiocarcinoma. Enrollment is listed as 24. The treatment plan specifies cisplatin (25 mg/m²), gemcitabine (1000 mg/m²), and copanlisib (60 mg) on days 1 and 8, with day 15 off, on an every 21-days schedule.
The primary outcome is median PFS, with a 95% confidence interval and a six-month timeframe. Response rate and overall survival are listed as secondary outcomes. Numerical results for these outcomes are not reported in the registry record. Safety entries list 12 participants affected by serious adverse events, 24 affected by other adverse events, and 18 deaths. The record does not report a comparative analysis, detailed analysis methods, or analysis populations.