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 Daily Oral Regorafenib for Chemotherapy-Refractory, Metastatic and Locally Advanced Angiosarcoma (NCT02048722), a na phase 2 study. The primary outcome is Progression-Free Survival (PFS) at 4 Months.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02048722 |
| Phase | Phase 2 |
| Condition | Adult Angiosarcoma, Recurrent Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 31 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Northwestern University |
| Results posted | Yes |
2. Clinical Question
The study asks whether daily oral regorafenib merits evaluation in people with angiosarcoma that has progressed after chemotherapy. The registry describes the treatment’s purpose as assessing whether it might be effective; it does not report an estimate of the primary outcome or a treatment effect.
Population
Adults with angiosarcoma described as chemotherapy-refractory, metastatic, or locally advanced. The registry also lists recurrent adult soft tissue sarcoma and stage III and stage IV adult soft tissue sarcoma among the conditions.
Intervention
Daily oral regorafenib. The treatment description specifies dosing on days 1-21, with courses repeating every 28 days while disease progression or unacceptable toxicity has not occurred.
Comparator
There is no concurrent comparator group: the study is single-group, open-label, and has no masking. Its allocation is listed as not applicable. The results therefore do not provide a randomized comparison with another treatment or a control.
Primary question
What is progression-free survival at 4 months among evaluable study patients? The endpoint is defined around the absence of progression at that time, with progression or death—whichever occurs first—counted as an event from treatment start.
The registry lists progression-free survival at 3 and 6 months, median progression-free survival, overall survival, response rate, tumor control, and related adverse events among secondary outcomes. These are additional questions, but their estimates are not reported in the registry record. Without outcome estimates, the clinical question can be described, but the magnitude and precision of any observed outcome cannot be assessed from this record.
3. Trial Design
This was a multicenter, open-label phase II study with a single treatment group. The registry lists 31 enrolled participants and identifies Northwestern University as the sponsor. The study status is completed. The registry records a start date of 2014-06-13 and a primary completion date of 2019-10-14.
All participants were assigned to the treatment group described as receiving oral regorafenib. The regimen was daily dosing on days 1-21, with courses repeating every 28 days in the absence of disease progression or unacceptable toxicity. No masking was used. Allocation is listed as not applicable because the design is not a randomized, multi-arm comparison.
The single-group structure is important for interpretation. Outcomes can describe what happened among participants receiving the study treatment, subject to the endpoint definitions and available follow-up. They cannot, by themselves, separate a treatment effect from other explanations for the observed course. There is no concurrent control group in the registry record against which to compare progression-free survival, response, or safety.
The primary endpoint is progression-free survival at 4 months. Secondary outcomes include progression-free survival at 3 and 6 months, median progression-free survival, overall survival, response rate, tumor control, and counts of related adverse events by grade. Although the registry lists seven outcome measures, it lists no analyses. Estimates for the primary and secondary outcomes are not reported in the registry record.
The registry does not report a sample-size justification, detailed statistical analysis plan, or interim-analysis plan. The enrollment count alone does not establish how the study’s size was chosen or what precision was expected. Planning illustrations based on an observed effect are not the study’s design justification and should not be interpreted as observed power.
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.
2 Cycles of Treatment
| Stage | Treatment (Regorafenib) |
|---|---|
| STARTED | 31 |
| Attempted 1st Cycle | 31 |
| Attempted 2nd Cycle | 23 |
| COMPLETED | 23 |
| NOT COMPLETED | 8 |
Reasons for not completing this period:
| Reason | Treatment (Regorafenib) |
|---|---|
| Adverse Event | 2 |
| Withdrawal by Subject | 4 |
| Progressive Disease | 2 |
Reached 1st Response/Continued Treatment
| Stage | Treatment (Regorafenib) |
|---|---|
| STARTED | 23 |
| Assessed for First Response | 23 |
| Went on to Cycle 3 and Beyond | 13 |
| COMPLETED | 13 |
| NOT COMPLETED | 10 |
Reasons for not completing this period:
| Reason | Treatment (Regorafenib) |
|---|---|
| Progressive Disease | 10 |
Follow up 5 Years or Cut of Timepoint
| Stage | Treatment (Regorafenib) |
|---|---|
| STARTED | 31 |
| COMPLETED | 4 |
| NOT COMPLETED | 27 |
Reasons for not completing this period:
| Reason | Treatment (Regorafenib) |
|---|---|
| Death | 24 |
| Withdrawal by Subject | 3 |
Analysis population for the primary outcome, as defined in the registry: 8 Patients were not included due to the following reasons: progressive disease, patient refused further treatment (withdrawal of consent for further treatment), toxicity. This was due to data having either missing time points or "cycle 1" or "Cycle 1: follow up" missing from the dataset at the time of the analysis.
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: This includes patients that started study treatment. Any patients who signed consent but never initiated treatment (screenfails) are not included.
| Characteristic | Unit | Treatment (Regorafenib) |
|---|---|---|
| Participants analysed | 31 | |
| Age, Customized | years | 64.32 (SD 14.58) |
| Sex: Female, Male: Female | Participants | 16 |
| Sex: Female, Male: Male | Participants | 15 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 31 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| 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 | 3 |
| Race (NIH/OMB): White | Participants | 27 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | participants | 31 |
| Type of disease: Metastatic | Participants | 21 |
| Type of disease: Locally advanced/Unresectable | Participants | 9 |
| Type of disease: Not reported | Participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-Free Survival (PFS) at 4 Months, measured over At 4 months (of treatment).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of patients alive |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is progression-free survival at 4 months. The registry defines it as the number of evaluable study patients without progression at that time divided by the total number of evaluable patients. It also states that the time-to-event measure begins at treatment start and ends at progression or death, whichever occurs first, and that the survival probability will be estimated using Kaplan-Meier methods.
Progression is assessed using RECIST v1.1. As described in the record, progressive disease includes a > 20% increase in the sum of target-lesion diameters relative to the smallest sum while on study, together with an absolute increase of 5 mm. The appearance of one or more new lesions also qualifies as progression. The record describes RECIST measurements as based on changes in the largest diameter of tumor lesions.
Progression-free survival is used to represent time until disease progression or death, rather than response alone. General statistical explanation: a time-to-event endpoint can incorporate both when an event occurs and the follow-up available for participants who have not yet had an event. Kaplan-Meier estimation is a method for estimating survival probabilities over time in that setting. Its interpretation depends on adequate follow-up and appropriate handling of censoring; those details are not reported in the registry record.
The registry’s unit wording refers to a percentage of patients alive, while its endpoint title and definition describe progression-free survival and specify progression or death as the event. The result estimate and confidence interval are not reported in the registry record, so the observed 4-month outcome and its precision cannot be evaluated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary question and the planned method, but it does not report the primary progression-free survival estimate or its 95% confidence interval. It also lists no analyses. Consequently, the available record does not establish the observed 4-month progression-free survival, its precision, or how the result relates to the study’s intended question.
The distinction between a planned endpoint and a reported result matters. A definition specifies what investigators intended to measure; it is not evidence of the outcome. In this study, progression-free survival is defined from treatment start until progression or death, whichever occurs first, and is to be estimated with Kaplan-Meier methods. The record does not give the resulting survival probability, an event count for that endpoint, or a confidence interval.
The primary outcome’s population is described as evaluable patients, but the size and detailed definition of that population are not reported. The record says 8 patients were not included for reasons involving progressive disease, refusal of further treatment or withdrawal of consent, and toxicity. It also notes missing time points or missing “cycle 1” or “Cycle 1: follow up” entries in the dataset at the time. These statements do not provide a complete accounting of the primary analysis population or explain how each reason affected inclusion.
The design also limits what an outcome could show. This was a single-group, open-label study, with no randomized comparator. A measured outcome in this group would describe participants treated in the study, but it would not provide a like-for-like estimate of what would have happened under another treatment or under a control condition. The registry does not report an adjusted or comparative analysis.
The registry lists secondary outcomes, including progression-free survival at 3 and 6 months, median progression-free survival, overall survival, response rate, tumor control, and related adverse events. Their estimates are not reported in the registry record. There is also no listed analysis plan to clarify how those endpoints were calculated, how missing observations were treated, or whether any multiplicity procedure was planned.
Safety information is available as counts of participants affected and serious-event terms with percentages. These are descriptive registry entries, not a comparison against another group. The serious-event listings do not establish that an event was caused by regorafenib, and the record does not provide enough detail to reconstruct event timing, duration, or participant-level overlap.
Overall, the registry supports a description of the study design, treatment schedule, endpoint definition, and selected safety counts. It does not provide the outcome estimates needed to judge the observed progression-free survival or the precision of that estimate. Neither the design nor the listed safety counts establish a causal treatment effect.
9. Statistical Methods Explained
The primary analysis is described as a time-to-event analysis. The starting point is treatment initiation. The event is progression or death, whichever occurs first. The target time point is 4 months, and the planned summary is a survival probability estimated using Kaplan-Meier methods. The registry additionally describes the endpoint as the number of patients without progression at 4 months divided by the total number of evaluable patients.
What does Kaplan-Meier estimation represent?
General statistical explanation: Kaplan-Meier estimation uses the observed timing of events to estimate the probability of remaining event-free over time. Participants who have not had an event by their last known follow-up may contribute information up to that point without being treated as if an event occurred. This is commonly called censoring. The method relies on assumptions about the relationship between censoring and the chance of the event. The registry identifies Kaplan-Meier as the planned method, but censoring rules, follow-up procedures, and diagnostics are not reported in the registry record.
The endpoint’s wording combines a fixed-time proportion with a time-to-event estimate. A simple fraction of evaluable patients without progression at 4 months and a Kaplan-Meier estimate can differ when follow-up is incomplete or participants are censored before that time. The registry says the outcome will be estimated using Kaplan-Meier methods but does not explain how the stated fraction and the time-to-event estimator are reconciled in the analysis. No estimate is available to clarify which value was reported.
How is progression defined?
The record cites RECIST v1.1 and says that measurements use changes in the largest diameter of tumor lesions. Progressive disease is defined as a > 20% increase in the sum of target-lesion diameters, taking the smallest sum on study as the reference, with an absolute increase of 5 mm also required. One or more new lesions also qualifies as progressive disease. These criteria determine when a progression event is counted for the primary endpoint, according to the registry description.
Death is also an event for progression-free survival, even if progression has not been recorded first. This means the endpoint captures time to the first of the two specified events; it is not simply a measure of tumor shrinkage or response. Response rate and tumor-control rate are listed separately as secondary outcomes, but their definitions and estimates are not reported in the registry record.
What does the confidence interval add?
The primary endpoint is described as a survival probability with a 95% confidence interval. General statistical explanation: a confidence interval communicates the uncertainty around an estimate under the method’s assumptions. A narrower interval generally indicates greater statistical precision, while a wider interval indicates less precision. It does not resolve limitations in the study design, missing data, or the absence of a comparator. The registry record does not report the interval’s endpoints, so the precision of the primary estimate cannot be assessed.
The registry does not report the planned sample-size justification, the expected event count, or a target precision for the primary endpoint. It lists 31 enrolled participants, but enrollment alone does not show how many were evaluable, how many had progression or death, or how much follow-up was available. It also does not establish the statistical power of the study.
Planning illustrations based on an observed effect use assumptions stated for those calculations: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The registry study itself is single-group, so those two-arm assumptions do not describe its design. For time-to-event illustrations, the stated quantity is total events; for other illustrations, it is participants per arm. Such planning values are hypothetical design calculations, not observed participant counts and not observed power. The registry does not report the study’s own sample-size rationale.
What analyses are available?
The record lists seven outcome measures but no analyses. It does not report an analysis population for each endpoint, a statistical model beyond the stated Kaplan-Meier method for the primary outcome, covariate adjustment, subgroup analyses, or sensitivity analyses. These details matter because analytic choices can affect estimates and uncertainty. In their absence, interpretation should stay with the design and endpoint definitions actually described.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes: progression-free survival at 4 months as the primary endpoint, along with progression-free survival at 3 and 6 months, median progression-free survival, overall survival, response rate, tumor control, and related adverse events by grade. The registry record does not report a multiplicity plan, such as whether the secondary outcomes were treated as exploratory or whether any adjustment for multiple statistical tests was planned. It also lists no analyses or outcome estimates. Therefore, the record does not support an assessment of how multiple endpoints were handled or how any reported statistical evidence would have been interpreted across them.
Information about missing data and analysis populations is limited. The primary endpoint refers to evaluable study patients, but the number evaluable and the operational definition of evaluability are not reported. The record states that 8 patients were not included, citing progressive disease, refusal of further treatment or withdrawal of consent, and toxicity. It also attributes this to data with missing time points or missing “cycle 1” or “Cycle 1: follow up” entries in the dataset at the time. The registry does not specify the number excluded for each reason, how the reasons map to the missing entries, or whether the exclusions applied to the primary endpoint alone or to other outcomes as well.
The record does not report how missing follow-up or missing outcome measurements were handled, whether participants were censored, or what assumptions were used for the Kaplan-Meier analysis. It also does not identify an intention-to-treat population or other named analysis population. These omissions limit assessment of potential bias from participant exclusions or incomplete follow-up. No sample-size justification, interim-analysis plan, or detailed statistical analysis plan is reported in the registry record.
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 |
|---|---|---|---|
| Treatment (Regorafenib) | 15 | 31 | 48.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (Regorafenib) | 24 of 31 |
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 |
|---|---|
| Treatment (Regorafenib) | 31 of 31 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment (Regorafenib) |
|---|---|---|
| Disease progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 2 of 31 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 31 |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | 1 of 31 |
| Intractable pain | General disorders | 1 of 31 |
| Vascular Disorder | Vascular disorders | 1 of 31 |
| Intra-abdominal hemorrhage | Gastrointestinal disorders | 1 of 31 |
| Peripheral sensory neuropathy | Nervous system disorders | 1 of 31 |
| Fever | General disorders | 1 of 31 |
| Nausea | Gastrointestinal disorders | 1 of 31 |
| Nausea | Gastrointestinal disorders | 1 of 31 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Regorafenib) |
|---|---|---|
| Fatigue | General disorders | 23 of 31 |
| Hypertension | Vascular disorders | 17 of 31 |
| Diarrhea | Gastrointestinal disorders | 16 of 31 |
| Nausea | Gastrointestinal disorders | 16 of 31 |
| Lymphocyte count decreased | Investigations | 16 of 31 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 16 of 31 |
| Anemia | Blood and lymphatic system disorders | 14 of 31 |
| Anorexia | Metabolism and nutrition disorders | 13 of 31 |
| Hypocalcemia | Metabolism and nutrition disorders | 13 of 31 |
| Constipation | Gastrointestinal disorders | 12 of 31 |
Serious events with the highest arm-level rate: disease progression (6.5%), dyspnea (3.2%), pleural effusion (3.2%), intractable pain (3.2%), vascular disorder (3.2%).
The safety entries describe the treatment group, with 31 participants at risk for both serious and other adverse events. The registry lists 15 participants affected by serious adverse events and 31 affected by other adverse events. It also lists 24 deaths. These are separate registry counts; the record does not explain overlap among categories or establish the timing or cause of each event.
The listed serious-event terms include Disease progression at 6.5%, and Dyspnea, Pleural Effusion, Intractable pain, Vascular Disorder, and Intra-abdominal hemorrhage, each at 3.2%. These percentages are presented as registry entries; the record does not provide term-specific participant counts or further detail for interpreting the percentages.
General statistical explanation: an adverse event recorded during a study is not automatically an event caused by the study treatment. The registry lists related adverse events as a secondary outcome, but the serious-event counts and terms do not, by themselves, establish causality. Nor can these single-group counts be compared with an untreated or alternative-treatment rate. The entries are descriptive and should be read alongside the limited reporting of timing, severity detail, and participant-level overlap.
12. What the Result Does, and Does Not, Mean
The record establishes that a multicenter, open-label phase II study evaluated daily oral regorafenib in a single group of people with chemotherapy-refractory angiosarcoma. It specifies the dosing schedule and identifies progression-free survival at 4 months as the primary endpoint. It also describes the endpoint’s event definition and planned Kaplan-Meier estimation.
The record does not report the primary endpoint estimate or its 95% confidence interval. It therefore does not show the observed 4-month progression-free survival or how precisely it was estimated. The listed secondary outcomes likewise have no reported estimates in the registry record. A planned measurement is not a reported finding, and the endpoint definition cannot substitute for outcome data.
Even if an outcome estimate were available, the single-group design would constrain its interpretation. Without a concurrent comparator, a descriptive result could not establish how outcomes would differ under another treatment or control condition. The open-label design also means masking was not used. This description does not determine whether any particular result is biased, but it underscores that the registry does not offer a randomized comparative estimate.
The safety counts indicate that serious and other adverse events were recorded among participants, and the registry lists several serious-event terms. Those entries do not demonstrate that regorafenib caused an event, nor do they establish a comparative safety profile. The number of deaths is reported, but the record does not supply the information needed to attribute them to treatment or to characterize their relationship to disease progression.
Accordingly, the registry supports a careful account of study conduct and selected safety reporting, not a conclusion about treatment benefit or harm. The observed clinical outcomes, their uncertainty, the analysis population, and important analysis details are not reported in the registry record. Statistical interpretation should remain bounded by those missing results and the absence of a control group.
13. Why This Trial Matters Statistically
This study illustrates why the endpoint definition, analysis population, and outcome estimate need to be read together. The primary question concerns progression-free survival at 4 months, but the record’s definition refers to evaluable patients while also specifying a Kaplan-Meier estimate. The number evaluable is not reported, and the stated exclusions and missing dataset entries leave uncertainty about who contributed to the primary analysis.
The endpoint also depends on how progression is assessed. The registry gives RECIST v1.1 criteria, including the required increase in target-lesion diameters and the role of new lesions, and it counts death as an event alongside progression. Those details make the endpoint more interpretable than a label alone. However, without the estimated survival probability and confidence interval, the outcome itself and its precision remain unknown.
The single-group design is another central statistical feature. It permits description of outcomes among treated participants but does not provide a randomized control comparison. The enrollment count and adverse-event counts can be reported descriptively; neither creates a treatment contrast. Planning illustrations based on an observed effect likewise cannot replace a trial-specific sample-size rationale or be interpreted as observed power.
Finally, the registry lists several secondary outcomes but no analyses or estimates and does not report a multiplicity plan. This prevents evaluation of how the wider set of outcomes was analyzed. The example highlights a general statistical principle: a detailed protocol question is not enough to judge evidence without results, uncertainty, population accounting, and a clear account of analysis choices.
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 registry record does not report the primary progression-free survival estimate or its 95% confidence interval, and it lists no analyses. As a result, neither the observed endpoint nor its precision can be reviewed. Estimates for the listed secondary outcomes are also not reported.
The primary endpoint population is described as evaluable, but its size and definition are not given. The record says 8 patients were not included and cites progressive disease, refusal of further treatment or withdrawal of consent, and toxicity, as well as missing time points or missing “cycle 1” or “Cycle 1: follow up” entries in the dataset at the time. It does not give a reason-by-reason accounting or explain the impact on each endpoint.
The registry does not report detailed follow-up, censoring rules, missing-data methods, analysis populations, or sensitivity analyses. It gives the primary endpoint’s Kaplan-Meier method but not enough detail to assess its implementation. The sample-size justification and interim-analysis plan are not reported in the registry record.
The single-group, open-label design has no concurrent randomized comparator. Thus, the record cannot provide a like-for-like comparison with another treatment or control. Safety entries are also descriptive: the record does not establish event causality, timing, overlap, or a comparative rate. These limitations restrict what can be concluded from the posted information, independently of the endpoint’s clinical importance.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Daily Oral Regorafenib for Chemotherapy-Refractory, Metastatic and Locally Advanced Angiosarcoma — NCT02048722.
- Registry record last updated 2022-04-25; status last verified 2022-03.
- Results first posted 2020-07-29.
- 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
The registry describes a completed, multicenter, open-label phase II study sponsored by Northwestern University. It enrolled 31 participants in a single treatment group receiving daily oral regorafenib on days 1-21, with courses repeating every 28 days while progression or unacceptable toxicity had not occurred. Masking was not used.
The primary endpoint was progression-free survival at 4 months, defined from treatment start to progression or death and planned for estimation using Kaplan-Meier methods. The registry lists secondary outcomes covering progression-free survival at 3 and 6 months, median progression-free survival, overall survival, response, tumor control, and related adverse events. It lists no analyses, and outcome estimates are not reported in the registry record.
Safety entries list 15 participants affected by serious adverse events, 31 by other adverse events, and 24 deaths. The design has no concurrent comparator, and the record’s information about exclusions, missing data, and analysis populations is limited.