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 An Open Label Multi-center Extension Study to Evaluate Long-term Safety/ Tolerability of Dovitinib in Patients With Solid Tumors Who Continue to Receive Treatment With Dovitinib (TKI258) in Novartis-sponsored Single Agent Dovitinib Studies Which Fulfilled the Requirements for the Primary Objective (NCT02116803), a non-randomized phase 2, phase 3 study. The primary outcome is Number of Participants With Adverse Events of Grades 3 and 4 Severity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02116803 |
| Phase | Phase 2, Phase 3 |
| Condition | Solid Tumors |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
People with solid tumors who had continued treatment with dovitinib, either alone or with fulvestrant, in a Novartis-sponsored single-agent dovitinib study that had fulfilled its primary-objective requirements. The extension included people considered by the investigator to be benefiting from continued dovitinib treatment. The registry reports enrollment of 12 participants.
Intervention
Continued dovitinib at the last assigned dose and regimen from the parent study, with further dose modifications at the investigator’s discretion under protocol and investigative-brochure guidance. For participants in the combination group, dovitinib continued with fulvestrant at the last assigned regimen, with dose modification also at investigator discretion.
Comparator
The registry lists a dovitinib group and a dovitinib-plus-fulvestrant group. This was not a randomized, like-for-like comparison: participants continued the treatment they had received in their parent study, and the record does not describe a control group assigned for this extension.
Primary question
The primary outcome was the number of participants with grade 3 or grade 4 adverse events, assessed until the last patient discontinued dovitinib, up to 30 months. The clinical question was about long-term safety and tolerability during continued treatment, rather than whether one regimen was more effective than another. The registry record does not report the endpoint count for grade 3 or grade 4 events.
3. Trial Design
This was an open-label, multicenter extension study with non-randomized allocation and a parallel-group model. Its purpose was to allow continued safety follow-up for participants who remained on dovitinib, alone or with fulvestrant, in earlier Novartis-sponsored studies. Eligibility for continued participation was tied to the parent study having fulfilled its primary-objective requirements and the investigator judging the participant to be benefiting from treatment. The extension therefore describes a selected group who continued treatment, not a newly assembled group representing all people with solid tumors.
The registry lists phase 2 and phase 3. Enrollment was 12. The study began on 2014-05-28, had primary completion on 2016-11-28, and is marked completed. Participants in the single-agent group continued their last assigned dovitinib dose and regimen from the parent study. The combination group continued dovitinib and fulvestrant from the parent study. Further dose modifications were at investigator discretion, guided by the protocol and investigative brochure.
Open-label means treatment assignment was not masked from participants or investigators. Non-randomized means the record does not describe random allocation to the two treatment groups. Because group membership followed prior treatment and participation in parent studies, differences between the groups cannot be interpreted as effects caused by adding fulvestrant. The registry record does not report more detail about the parent studies, the criteria used to judge ongoing benefit, or a separate control strategy for the extension.
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 | Dovitinib | Dovitinib + Fulvestrant |
|---|---|---|
| STARTED | 10 | 2 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 10 | 2 |
Reasons for not completing this period:
| Reason | Dovitinib | Dovitinib + Fulvestrant |
|---|---|---|
| Adverse Event | 2 | 1 |
| Physician Decision | 1 | 0 |
| Progressive disease | 4 | 0 |
| Study terminated by sponsor | 2 | 1 |
| Death | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety set: the Safety set included all patients who received at least one dose of study medication. Safety set was identical to Full Analysis Set for this study.
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: Full analysis set (FAS): all patients who received at least one dose of study medication.
| Characteristic | Unit | Dovitinib | Dovitinib + Fulvestrant | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 2 | 12 | |
| Age, Continuous | Years | 60.3 (SD 10.55) | 72.0 (SD 14.14) | 62.3 (SD 11.40) |
| Sex: Female, Male: Female | Participants | 3 | 2 | 5 |
| Sex: Female, Male: Male | Participants | 7 | 0 | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events of Grades 3 and 4 Severity, measured over Until the last patient discontinued dovitinib up to 30 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the number of participants with adverse events of grade 3 or grade 4 severity. Severity was assessed using CTCAE Version 4.03, unless otherwise specified. Events were organized by System Organ Class, and a participant with multiple events within one primary system organ class was counted once in the total row. The endpoint therefore concerns participants experiencing qualifying events, rather than the total number of event episodes.
As a general statistical point, a participant-level count can summarize how commonly severe events occurred within the safety population while avoiding repeated counting of one person for multiple events in the same category. It does not, by itself, describe how long events lasted, how often they recurred, or the total burden of all event episodes. The registry defines the assessment window as lasting until the last patient discontinued dovitinib, up to 30 months.
The endpoint is relevant to a study focused on long-term safety and tolerability because it captures serious degrees of severity during continued exposure. However, the posted record does not give the number of participants meeting this grade 3 or grade 4 endpoint. The serious adverse-event figures listed elsewhere in the record are not interchangeable with this severity endpoint: seriousness and severity are distinct classifications, and the record does not establish that every serious event was grade 3 or grade 4.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes 12 enrolled participants across two continuing-treatment groups: dovitinib and dovitinib plus fulvestrant. The posted adverse-event counts identify 10 participants at risk in the dovitinib group and 2 in the combination group. For serious adverse events, 4 participants in the dovitinib group and 2 in the combination group were affected. In the registry’s other-adverse-event category, 9 participants in the dovitinib group and 2 in the combination group were affected. These are descriptive counts from a small extension population, not estimates from a randomized comparison.
The denominators differ between the groups, and the treatment groups were not formed by random allocation. Participants continued the regimens they had received in parent studies, and enrollment depended on ongoing treatment and investigator judgment that participants were benefiting. As a result, the group counts should not be read as evidence that one regimen caused more or fewer adverse events than the other. The record does not provide an adjusted comparison, a test of group differences, or a confidence interval for these counts.
The registry’s primary endpoint is the number of participants with grade 3 or grade 4 adverse events. Its posted results do not include that endpoint count. The serious-event counts therefore do not fill this gap: seriousness is a separate classification from severity grade. Nor should the other-adverse-event counts be assumed to mean events below grade 3, because the record does not make that mapping.
The listed serious-event terms include acute myocardial infarction and adenocarcinoma of colon, each reported as 50.0%, as well as bradycardia, coronary artery disease, myocardial ischaemia, and pneumonia, each reported as 10.0%. These percentages are registry-listed event-term figures; the record does not give the participant counts underlying each term or enough detail to determine how categories may overlap. They should not be added together or treated as a summary rate.
There is no inferential analysis reported in the registry record. Thus, the posted counts describe events among participants who continued treatment in this extension; they do not establish comparative treatment effects, event rates in a broader population, or the relationship between treatment and any individual event. The small, selected, non-randomized sample and lack of a reported primary endpoint count limit how precisely safety can be characterized from this record.
9. Statistical Methods Explained
The registry describes a participant-count endpoint: the number of people with grade 3 or grade 4 adverse events. A count of participants differs from a count of event episodes. If one person has multiple events within a primary system organ class, the registry says that person is counted once in the total row for that class. This avoids treating repeated events in the same class as if they came from separate participants. It also means the endpoint does not communicate the full number of episodes or their duration.
What does a confidence interval add?
As a general statistical explanation, a confidence interval expresses the uncertainty around an estimated quantity. It helps readers distinguish a relatively precise estimate from one that could plausibly vary widely because the amount of information is limited. The registry record does not report confidence intervals for the adverse-event counts, and no interval can be inferred from the listed counts alone without choosing and applying an analysis method.
Why does the study design matter?
Random assignment can make treatment groups more comparable on average by distributing known and unknown baseline characteristics through the assignment process. This extension was non-randomized. Participants entered while continuing regimens received in parent studies, and the investigator’s assessment that they were benefiting was part of the setting described in the record. The groups may therefore differ for reasons other than regimen. A direct numerical contrast between them would not isolate a treatment effect, even if a statistical test were calculated.
Open-label status means participants and investigators knew the treatment being received. In general, this can influence decisions and reporting related to care or event assessment. The registry identifies CTCAE Version 4.03 as the severity framework, unless otherwise specified, but does not report masking of event assessment or additional procedures intended to reduce assessment bias.
What can event counts establish?
Counts convey how many participants were recorded with an event in the stated groups. They do not automatically account for differences in time on treatment. Although the endpoint timeframe extends until the last patient discontinued dovitinib, up to 30 months, the record does not provide individual exposure durations or person-time. A count alone consequently cannot be interpreted as an exposure-adjusted rate. The registry also does not report a time-to-event analysis for these safety outcomes.
The serious adverse-event count and the grade 3 or grade 4 primary endpoint represent different classifications. An event may be classified by seriousness and separately assigned a severity grade. Since the registry does not provide a cross-tabulation or say that the categories coincide, the serious-event counts cannot be substituted for the missing primary endpoint result. The listed serious-event terms also do not give a complete account of the primary endpoint.
How should the planning illustration be understood?
The record’s stated planning assumptions describe an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are hypothetical planning exercises, not observed trial results or evidence of the study’s actual power. The sample-size assumptions explicitly distinguish planning from the trial’s own design. The registry record does not report a sample-size justification for the extension, or a statistical analysis plan supporting a confirmatory comparison.
More broadly, a small count of participants can make estimates sensitive to the experience of individual participants. That general limitation is especially important when one group contains only 2 participants at risk. The record reports counts but no inferential analysis; statistical significance, precision, or equivalence between groups should not be inferred from these descriptive figures.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure and reports no analyses. It does not report a multiplicity-control procedure, a hierarchy of hypotheses, or an adjustment for examining multiple outcomes or event categories. Since no inferential results are posted, there are no reported p-values whose interpretation would depend on a stated multiplicity strategy. The record does not say whether any additional analyses were planned or performed outside the posted results.
The safety population is defined as all patients who received at least one dose of study medication. The registry says this population was identical to the Full Analysis Set for this study. That definition clarifies who was intended to contribute to the reported safety summaries. It does not, by itself, explain how missing event information, incomplete follow-up, or withdrawal was handled.
Missing-data procedures are not reported in the registry record. The record does not state whether participants with incomplete follow-up were excluded from particular summaries, how missing assessments were treated, or whether sensitivity analyses were conducted. The endpoint timeframe runs until the last patient discontinued dovitinib, up to 30 months, but no participant-level follow-up details are given. The number and timing of discontinuations are not reported in the registry record.
With no reported analysis plan or inferential results, readers cannot assess whether analysis decisions were prespecified, whether all planned outcomes were posted, or how uncertainty was quantified. These omissions do not change the descriptive counts, but they limit interpretation beyond those counts.
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 |
|---|---|---|---|
| Dovitinib | 4 | 10 | 40.0% |
| Dovitinib+Fulvestrant | 2 | 2 | 100.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dovitinib | 9 of 10 |
| Dovitinib+Fulvestrant | 2 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | Dovitinib | Dovitinib+Fulvestrant |
|---|---|---|---|
| ACUTE MYOCARDIAL INFARCTION | Cardiac disorders | 0 of 10 | 1 of 2 |
| BRADYCARDIA | Cardiac disorders | 1 of 10 | 0 of 2 |
| CORONARY ARTERY DISEASE | Cardiac disorders | 1 of 10 | 0 of 2 |
| MYOCARDIAL ISCHAEMIA | Cardiac disorders | 1 of 10 | 0 of 2 |
| PNEUMONIA | Infections and infestations | 1 of 10 | 0 of 2 |
| ADENOCARCINOMA OF COLON | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 10 | 1 of 2 |
| PLEURAL EFFUSION | Respiratory, thoracic and mediastinal disorders | 1 of 10 | 0 of 2 |
| PNEUMOTHORAX | Respiratory, thoracic and mediastinal disorders | 1 of 10 | 0 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dovitinib | Dovitinib+Fulvestrant |
|---|---|---|---|
| DECREASED APPETITE | Metabolism and nutrition disorders | 5 of 10 | 0 of 2 |
| DIARRHOEA | Gastrointestinal disorders | 3 of 10 | 1 of 2 |
| ANGINA PECTORIS | Cardiac disorders | 2 of 10 | 1 of 2 |
| CONSTIPATION | Gastrointestinal disorders | 3 of 10 | 0 of 2 |
| FATIGUE | General disorders | 2 of 10 | 1 of 2 |
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | 3 of 10 | 0 of 2 |
| RASH | Skin and subcutaneous tissue disorders | 3 of 10 | 0 of 2 |
| ANAEMIA | Blood and lymphatic system disorders | 2 of 10 | 0 of 2 |
| NAUSEA | Gastrointestinal disorders | 1 of 10 | 1 of 2 |
| OEDEMA PERIPHERAL | General disorders | 2 of 10 | 0 of 2 |
Serious events with the highest arm-level rate: acute myocardial infarction (50.0%), adenocarcinoma of colon (50.0%), bradycardia (10.0%), coronary artery disease (10.0%), myocardial ischaemia (10.0%).
The serious adverse-event group counts list 10 participants at risk in the dovitinib group, of whom 4 were affected, and 2 at risk in the dovitinib-plus-fulvestrant group, of whom 2 were affected. In the other-adverse-event category, 9 of the 10 participants at risk in the dovitinib group and 2 of the 2 at risk in the combination group were affected. These are counts within the registry’s safety summaries, not comparative estimates from randomized groups.
The serious-event terms listed are acute myocardial infarction (50.0%), adenocarcinoma of colon (50.0%), bradycardia (10.0%), coronary artery disease (10.0%), myocardial ischaemia (10.0%), and pneumonia (10.0%). The registry record does not provide the participant counts behind each term or clarify overlap among terms. The percentages therefore should be read as the posted term-specific figures, not added into a combined percentage.
Seriousness should not be treated as synonymous with grade 3 or grade 4 severity. The primary endpoint’s grade 3 or grade 4 count is not reported. Deaths are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The posted safety data show that adverse events were recorded among participants who continued dovitinib, either alone or with fulvestrant, in an extension study. The registry provides group counts for serious adverse events and for its other-adverse-event category, along with several serious-event terms and percentages. These figures describe the participants included in the safety summaries; they are not estimates from a controlled comparison.
The figures do not establish that one regimen is safer than the other. Treatment was not randomly assigned, the groups were drawn from participants continuing different parent-study regimens, and the group sizes were unequal. Differences in underlying participant characteristics, prior treatment, follow-up, or exposure could contribute to differences in recorded counts. The record does not provide an adjusted analysis to address such factors.
The counts also do not show that treatment caused any listed event, nor do they establish that an event was unrelated to treatment. The registry does not report the primary endpoint count for grade 3 or grade 4 adverse events, and serious adverse events cannot be substituted for that result. It also does not provide enough information to estimate exposure-adjusted event rates or describe the timing and duration of events.
In general, a safety extension can document events during continued treatment in the participants who remain eligible and enrolled. Its findings are most directly descriptive of that selected group and follow-up period. The posted data do not establish safety for all people with solid tumors, for people who did not continue treatment, or for people receiving other regimens. No medical decision should be based on these counts alone.
13. Why This Trial Matters Statistically
This record illustrates why study design and endpoint definitions matter when interpreting safety data. The extension addresses long-term safety and tolerability in participants who continued treatment after earlier studies had met their primary-objective requirements. That context helps explain what the observed counts represent: ongoing exposure in a selected group, rather than a new randomized comparison among all potentially eligible patients.
It also highlights the distinction between an event count and an inferential result. The registry posts descriptive counts for serious and other adverse events, but no analyses. It names a primary endpoint based on grade 3 or grade 4 severity without posting the endpoint count. Reporting a clearly defined outcome is valuable, but interpretation remains limited when the corresponding result is absent.
The separate concepts of seriousness and severity are statistically and clinically important. Treating them as interchangeable would risk answering a different question from the one named as primary. Likewise, percentages attached to serious-event terms cannot be combined without knowing the underlying counts and overlap.
Finally, non-randomized extension studies provide a useful record of what occurred among continuing participants, but their group comparisons are vulnerable to selection and baseline differences. The registry’s small enrollment and unequal group sizes make caution particularly important. The study is informative as descriptive follow-up, while the posted record does not support a causal comparison between the regimens.
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.
This extension enrolled 12 participants, with 10 at risk in the dovitinib group and 2 at risk in the dovitinib-plus-fulvestrant group. The small groups limit the amount of information available, and the combination group’s counts are especially sensitive to the experience of individual participants. The registry does not report confidence intervals or other measures of uncertainty for the posted safety counts.
Allocation was non-randomized, and participants continued regimens from parent studies. Entry also depended on investigator judgment that treatment was still benefiting the participant. The resulting population is selected, and the groups are not suitable as like-for-like controls. The registry record does not describe baseline characteristics that might help readers assess group comparability.
The primary endpoint count for grade 3 or grade 4 adverse events is not reported, even though the endpoint is defined. The serious adverse-event counts do not resolve this omission because seriousness and severity are distinct. The record does not report event-level counts behind the serious-event percentages, exposure-adjusted rates, participant-level time on treatment, or the handling of incomplete follow-up.
The registry also does not report a statistical analysis plan, inferential analyses, multiplicity procedures, or details of missing-data handling. Further details about the parent studies and the basis for investigator assessments of ongoing benefit are not reported in the registry record. These limitations constrain both precision and generalizability, and they prevent a causal interpretation of differences between the posted groups.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Open Label Multi-center Extension Study to Evaluate Long-term Safety/ Tolerability of Dovitinib in Patients With Solid Tumors Who Continue to Receive Treatment With Dovitinib (TKI258) in Novartis-sponsored Single Agent Dovitinib Studies Which Fulfilled the Requirements for the Primary Objective — NCT02116803.
- Registry record last updated 2018-03-01; status last verified 2018-01.
- Results first posted 2018-02-01.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT02116803 is a completed, open-label, multicenter extension study listed as phase 2 and phase 3. It enrolled 12 participants with solid tumors who continued dovitinib alone or with fulvestrant after treatment in Novartis-sponsored parent studies. The study began on 2014-05-28, with primary completion on 2016-11-28.
The primary endpoint was the number of participants with grade 3 or grade 4 adverse events, assessed until the last patient discontinued dovitinib, up to 30 months. The registry record does not report that endpoint count. It does post descriptive counts for serious and other adverse events, but no inferential analyses. Because allocation was non-randomized and the groups were not like-for-like controls, the counts should not be interpreted as a causal comparison between regimens.