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 A Phase II Study of Axitinib in Patients With Metastatic Renal Cell Cancer Unsuitable for Nephrectomy (NCT01693822), a na phase 2 study. The primary outcome is Freedom From Progression at 6 Months.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01693822 |
| Phase | Phase 2 |
| Condition | Clear-cell Metastatic Renal Cell Carcinoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 65 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Institute of Cancer Research, United Kingdom |
| Results posted | Yes |
2. Clinical Question
The clinical question concerns the activity of axitinib in people with clear-cell metastatic renal cell carcinoma whom their treating clinician judged unsuitable for nephrectomy. The study record identifies freedom from progression at six months as the primary endpoint, and describes additional outcomes concerning response, survival, safety, toxicity, and whether participants became suitable for nephrectomy during therapy.
Population
People with clear-cell metastatic renal cell carcinoma judged by the treating clinician to be unsuitable for nephrectomy. The registry record lists enrollment of 65 participants.
Intervention
Axitinib, described as an oral tablet taken twice daily. The arm description gives a starting dose of 5mg and says treatment continued until disease progression; the broader summary describes treatment according to tolerability for as long as participants were deriving clinical benefit.
Comparator
No comparator arm is listed. The study is recorded as single group, with allocation marked NA and masking marked none. It is therefore not a randomized comparison against another treatment or a control group.
Primary question
What proportion of participants were alive and progression free at six months after study entry? Progression was defined using confirmed progressive disease according to RECIST v1.1, or death, with progression-free participants censored at their last follow-up.
The registry record describes evaluation of efficacy, safety, toxicity, and biomarker changes during therapy. Blood and tumour tissue sampling before and during therapy is mentioned in the study summary, but the record does not report biomarker results. The primary clinical objective is described as defining axitinib activity in this population. Because there is no concurrent comparator, the study can describe outcomes observed among participants receiving axitinib, but it cannot isolate the treatment effect from other explanations for those outcomes.
3. Trial Design
This is a Phase II, single-group study of axitinib in metastatic renal cell carcinoma. The registry record lists the condition as clear-cell metastatic renal cell carcinoma, enrollment as 65, and the study status as completed. It records a start date of 2012-10 and a primary completion date of 2017-03. The sponsor is the Institute of Cancer Research, United Kingdom.
The record lists no allocation and no masking. The single-group design means participants were not assigned within this study to axitinib versus a control arm. Consequently, there is no randomized within-trial estimate of the difference between axitinib and another treatment or no treatment. Outcomes can be reported for the treated group, but interpretation must account for the absence of a like-for-like control group.
Axitinib is described as an oral tablet taken twice daily. The arm description specifies a starting dose of 5mg and says treatment continued until disease progression. The broader study summary says dosing was according to tolerability and treatment continued for as long as participants were deriving clinical benefit. These descriptions state the registry’s treatment information; further dose-modification rules and the exact operational stopping criteria are not reported in the registry record.
The primary endpoint is freedom from progression at six months. The record defines progression from study entry until the first of death or confirmed progressive disease according to RECIST v1.1. Participants alive and without progression were to be censored at last follow-up. Progression-free survival was also described as being presented using the Kaplan Meier product limit method, with median progression-free survival reported. A blinded central review of CT scans is described as a verification procedure.
Other outcomes listed include best overall response, progression-free survival, overall survival, safety and toxicity graded using NCI CTC Grading Version 4, and the number of participants who became suitable for nephrectomy as a consequence of therapy. The registry record does not report the numerical results for these outcomes in the information available for this analysis. Further design details, including the sample-size justification and a full statistical analysis plan, are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Axitinib |
|---|---|
| STARTED | 65 |
| COMPLETED | 65 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Reporting group
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: ITT
| Characteristic | Unit | Axitinib |
|---|---|---|
| Participants analysed | 65 | |
| Age, Continuous | years | 63.5 (56.7 to 69.0) |
| Age, Customized: 40-49 years | Participants | 8 |
| Age, Customized: 50-59 years | Participants | 19 |
| Age, Customized: 60-69 years | Participants | 26 |
| Age, Customized: 70+ years | Participants | 12 |
| Sex: Female, Male: Female | Participants | 22 |
| Sex: Female, Male: Male | Participants | 43 |
| Race and Ethnicity Not Collected | Participants | — |
| Histological type: Clear cell | Participants | 62 |
| Histological type: Clear cell and chromophobe | Participants | 2 |
| Histological type: Clear cell and sarcomatoid component | Participants | 1 |
| Fuhrman grade: G1 - inconspicuous nucleoli at ×400 magnification and basophilic (low-grade) | Participants | 2 |
| Fuhrman grade: G2 - clearly visible nucleoli at ×400 magnification and eosinophilic (low-grade) | Participants | 26 |
| Fuhrman grade: G3 - clearly visible nucleoli at ×100 magnification (high grade) | Participants | 21 |
| Fuhrman grade: G4 - extreme pleomorphism or rhabdoid and/or sarcomatoid morphology (high grade and most aggressive) | Participants | 2 |
| Fuhrman grade: Unobtainable | Participants | 14 |
| Motzer Score: Intermediate risk (1-2 risk factors) | Participants | 50 |
| Motzer Score: High risk (3+ risk factors) | Participants | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Freedom From Progression at 6 Months, measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage |
| Endpoint classification | not reduced to a single comparison |
Freedom from progression at six months is the proportion of study participants who were alive and had not experienced disease progression at the specified time point. The registry record identifies the assessment as the day 1 week 25 visit. It defines the progression-free interval from study entry, using the first occurrence of death or confirmed progressive disease according to RECIST v1.1. Participants still alive and free from progression were to be censored at the date of their last follow-up.
This endpoint combines two clinically important events—death and disease progression—into a time-to-event outcome. A fixed-time proportion offers a readily interpretable description of the share of the study group meeting the endpoint at a stated follow-up point. The accompanying confidence interval is intended to express uncertainty about that estimated proportion. In general, a confidence interval describes the range of values compatible with the observed data under the method’s assumptions; it does not guarantee that the true value lies within a particular interval.
The record also describes a Kaplan Meier presentation of progression-free survival, with a median to be reported. In general, a Kaplan Meier estimate uses each participant’s observed follow-up time and accounts for censoring, rather than treating everyone as if they had the same length of observation. The six-month proportion and the full time-to-event curve answer related but distinct questions: one focuses on a specified time point, while the other describes estimated event-free survival over follow-up.
The registry record does not report the six-month estimate, its 95% confidence interval, the median progression-free survival, or the underlying event and censoring counts. The endpoint definition and planned method can therefore be described, but the observed efficacy result cannot be interpreted from this record alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a defined primary endpoint and describes how progression and censoring were to be handled, but it does not report the endpoint estimate. In particular, the numerical proportion alive and progression free at six months and its 95% confidence interval are not reported in the registry record. No conclusion about the observed level or precision of six-month freedom from progression can be drawn from the information. The record also does not give the median progression-free survival or numerical results for best overall response and overall survival.
Design is central to interpretation. The study is listed as single group, with no allocation and no masking. As a result, its outcomes are observations among participants treated with axitinib, rather than a direct randomized comparison. Without a concurrent control group, differences between participants’ outcomes and what might have happened under another treatment or no study treatment cannot be estimated within this trial. Patient selection, disease course, follow-up, and other factors may also contribute to observed outcomes. These are general limitations of interpreting an uncontrolled treatment group; the registry does not quantify their contribution.
The six-month endpoint is framed as a proportion, with a 95% confidence interval specified in the endpoint description. A confidence interval would communicate statistical uncertainty around the estimate, but neither the estimate nor the interval is reported. The intended Kaplan Meier analysis of progression-free survival would incorporate varying follow-up and censoring, but the registry record does not supply a survival curve, a median, or sufficient event and follow-up details to assess the resulting estimate.
The safety information is separate from evidence of efficacy. In the Axitinib group, 64 participants are listed as at risk for serious adverse events and 26 as affected. For other adverse events, 64 are listed as at risk and 64 as affected. The record lists 62 deaths. These counts do not establish why events occurred, whether they were caused by axitinib, or how they relate to disease progression. The record does not provide the timing, duration, individual participant histories, or a comparison group needed to interpret those counts as comparative risks.
The listed serious adverse event terms include Pyrexia, Dyspnoea, Back pain, Fatigue, Pain, and Diarrhoea, with percentages attached to each term. Those percentages describe the registry’s reported entries; they do not, by themselves, establish causation or provide a complete account of each participant’s experience. The registry record’s stated primary objective was to define activity, but the absent endpoint result means that the objective’s numerical outcome is unavailable. The posted information supports a description of the design, endpoint definition, and selected safety counts—not a claim that axitinib did or did not produce a particular benefit or harm.
9. Statistical Methods Explained
The study record identifies a proportion alive and progression free at six months as its primary endpoint. The outcome is defined using time from study entry to the first of death or confirmed progressive disease according to RECIST v1.1. In general, an endpoint definition matters because it specifies which events count, when observation begins, and how follow-up is treated. A clear definition makes it possible to distinguish the intended outcome from other measures such as response at a single assessment or overall survival.
What does censoring mean?
The registry says participants who were alive and free from progression were censored at their last follow-up. In general, censoring means that the exact time to an event is not observed for a participant during the available follow-up, even though the participant contributes information up to the last known observation. A censored participant is not automatically treated as having experienced progression or death. The interpretation of a time-to-event analysis depends on the assumptions behind censoring, including whether the reason follow-up ends is related to the participant’s unobserved future event time. The record states the censoring rule, but it does not report follow-up distributions or reasons for loss of observation.
How should the six-month proportion be read?
A proportion at a fixed time point describes the share of participants estimated to be alive and progression free at that point. The registry specifies a 95% confidence interval for this proportion. In general, a confidence interval represents uncertainty in an estimate under a statistical method and its assumptions. A narrower interval indicates greater statistical precision than a wider interval, but precision is not the same as freedom from bias. The numerical estimate and interval are not reported in the registry record, so neither the magnitude nor precision of the result can be assessed.
What does Kaplan Meier add?
The record describes presenting progression-free survival with the Kaplan Meier product limit method and reporting a median. In general, Kaplan Meier estimation uses the timing of events and accommodates censored observations when estimating the probability of remaining event free over time. This differs from simply dividing the number of participants without an event at the endpoint by the original group size, because participants may have different lengths of follow-up. A median time-to-event is the time by which the estimated event-free proportion has reached one half, if the observed curve permits that value to be estimated. The registry record does not report the curve or median, so it is not possible to describe how those estimates turned out.
Why is central review mentioned?
The record says a blinded central review of CT scans would be conducted for verification. In general, independent or blinded review can help assess consistency in image-based disease evaluations, because reviewers who are unaware of other information may be less influenced by expectations. The registry describes this as a verification procedure; it does not report the central review’s findings, agreement with local assessments, or whether the review changed endpoint classifications.
What does the study design allow?
The design is listed as single group, with allocation marked NA and masking marked none. A single-group study can describe outcomes among participants receiving the intervention, but it does not create a randomized counterfactual group. Randomization in a comparative trial is generally used to balance measured and unmeasured prognostic factors across treatment groups in expectation. Without that comparison, observed outcomes cannot alone show what would have happened to the same participants under an alternative. This is a general design limitation, not a numerical finding about this trial.
The registry includes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. For time-to-event outcomes, the illustration is described as using a total event count, while other outcomes are described in terms of participants per arm. Such planning calculations are hypothetical illustrations, not observed power, and their assumptions do not convert this single-group study into a two-arm randomized trial. The underlying planning outputs and the trial’s own sample-size justification are not reported in the registry record.
Over-dispersion is a general issue for count outcomes when variation exceeds what a simple count model expects; if present and ignored, uncertainty can be understated. The record identifies the primary measure as a percentage and does not report a count-model analysis for it, so over-dispersion is not a reported feature of this endpoint. More generally, a method should match the outcome type and design. The registry information does not provide enough detail to assess model diagnostics, alternative analyses, or sensitivity analyses.
Statistical significance, if reported, would not by itself convey the clinical importance or precision of an effect. Estimates, uncertainty intervals, endpoint definitions, and study design need to be considered together. In this record, the central endpoint estimate and interval are absent, and no randomized comparison is available. The supported interpretation is therefore limited to the prespecified endpoint description and the analysis approach described in the registry.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint of freedom from progression at six months and also names secondary outcomes: best overall response, progression-free survival, overall survival, safety and toxicity using NCI CTC Grading Version 4, and the number of participants who became suitable for nephrectomy as a consequence of axitinib therapy. It records six outcome measures and zero analyses. The numerical results for these outcomes are not reported in the registry record.
When a study examines multiple outcomes or multiple statistical tests, the chance of at least one apparently unusual result can increase. This is the general multiple-comparisons problem. Researchers may address it through a prespecified testing hierarchy, adjustment procedures, or by treating secondary findings as exploratory. The registry record does not report a multiplicity strategy, a testing hierarchy, or which outcomes, if any, were formally tested. It is therefore not possible to determine how any unreported secondary findings would have been handled statistically.
The endpoint description specifies censoring at last follow-up for participants alive and free from progression. That is the only missing-follow-up detail given for the primary endpoint. The record does not report a broader missing-data plan, the number of participants with incomplete endpoint information, reasons for missing assessments, imputation methods, or sensitivity analyses. These omissions matter because incomplete observation can affect estimates when the likelihood or timing of missingness is related to prognosis or outcome.
The registry record does not specify analysis populations, such as whether results were to use all registered participants, a treated group, or another defined set. Nor does it report exclusions from analysis or how treatment discontinuations were handled. Such details are important for understanding who contributes to each estimate and whether the analysis corresponds to the study’s intended population. The record’s endpoint definition and censoring statement provide some methodological information, but they do not replace a complete statistical analysis plan.
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 |
|---|---|---|---|
| Axitinib | 26 | 64 | 40.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Axitinib | 62 of 64 |
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 |
|---|---|
| Axitinib | 64 of 64 |
Most frequent serious adverse event terms
| Event term | Organ system | Axitinib |
|---|---|---|
| Pyrexia | General disorders | 4 of 64 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 4 of 64 |
| Back pain | Musculoskeletal and connective tissue disorders | 4 of 64 |
| Fatigue | General disorders | 3 of 64 |
| Pain | General disorders | 3 of 64 |
| Diarrhoea | Gastrointestinal disorders | 3 of 64 |
| Pneumonia | Infections and infestations | 3 of 64 |
| Nausea | Gastrointestinal disorders | 2 of 64 |
| Infection | Infections and infestations | 2 of 64 |
| Sepsis | Infections and infestations | 2 of 64 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Axitinib |
|---|---|---|
| Fatigue | General disorders | 61 of 64 |
| Hypertension | Vascular disorders | 60 of 64 |
| Decreased appetite | Metabolism and nutrition disorders | 45 of 64 |
| Diarrhoea | Gastrointestinal disorders | 38 of 64 |
| Nausea | Gastrointestinal disorders | 38 of 64 |
| Proteinuria | Renal and urinary disorders | 38 of 64 |
| Back pain | Musculoskeletal and connective tissue disorders | 37 of 64 |
| Mucosal inflammation | General disorders | 32 of 64 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 29 of 64 |
| Weight decreased | Investigations | 28 of 64 |
Serious events with the highest arm-level rate: pyrexia (6.2%), dyspnoea (6.2%), back pain (6.2%), fatigue (4.7%), pain (4.7%).
The registry lists safety counts for the Axitinib group. It records 64 participants at risk for serious adverse events and 26 affected. For other adverse events, it records 64 at risk and 64 affected. The death count is 62. The record does not state in this information the observation window for these totals, the timing of individual events, or the causes of death. The counts should therefore be read as registry-reported safety figures, not as a comparison of risk between treatments.
Listed serious adverse event terms and percentages are Pyrexia, 6.2%; Dyspnoea, 6.2%; Back pain, 6.2%; Fatigue, 4.7%; Pain, 4.7%; and Diarrhoea, 4.7%. These entries identify reported serious-event terms; they do not show whether a term was judged related to axitinib, how long it lasted, how severe it was for an individual, or whether participants experienced more than one event. The registry record does not report those details.
Serious adverse events and all other adverse events are distinct reporting categories. The counts do not establish that the intervention caused an event, and without a comparator they cannot show whether event frequency was higher or lower than under another treatment. They also should not be used alone to infer treatment benefit or overall safety. Complete interpretation would require fuller event definitions, follow-up, attribution, and participant-level context, which are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The study record establishes that a Phase II, single-group study evaluated axitinib in people with clear-cell metastatic renal cell carcinoma considered unsuitable for nephrectomy. It defines freedom from progression at six months as the primary endpoint and describes the event definition, censoring rule, confidence interval, and intended Kaplan Meier presentation. Those details clarify what the study was designed to measure and how the endpoint was framed.
The record does not report the numerical primary endpoint result or its 95% confidence interval. It also does not report numerical findings for the other listed efficacy outcomes. Consequently, the available information cannot establish the observed six-month progression-free proportion, its precision, or the duration of progression-free survival. It cannot support a claim that axitinib did or did not provide a particular level of benefit.
The single-group design also sets a limit on causal interpretation. Any outcomes among participants receiving axitinib would describe that group, but no randomized comparison is listed to estimate what would have happened under an alternative. General factors such as participant selection and the natural course of disease can influence outcomes in an uncontrolled study. The registry information does not quantify these factors or separate their contribution from treatment effects.
The reported safety counts provide selected information about adverse events and deaths, but do not establish causation or comparative safety. The serious event terms and percentages are not a substitute for participant-level timelines, attribution, and a control group. Biomarker sampling is mentioned in the study summary, but biomarker results are not reported in the registry record. Overall, the record supports understanding the study question and its stated methods, while the absent outcome results and comparator restrict conclusions about efficacy and comparative harms.
13. Why This Trial Matters Statistically
This trial is statistically notable as a single-group Phase II study with a time-to-event primary endpoint framed at a fixed follow-up point. It illustrates the distinction between defining an outcome and reporting its result: the registry gives the six-month freedom-from-progression definition, event rules, and intended uncertainty measure, but not the estimate or confidence interval. A clearly specified endpoint is useful for interpreting a result, but it cannot substitute for the result itself.
The endpoint also shows how fixed-time and time-to-event summaries complement one another. A six-month proportion focuses on status at a particular point, while a Kaplan Meier analysis is intended to use event times and censoring across follow-up. In general, this can make use of follow-up information that a single fixed-time count does not capture. Their interpretation still depends on complete reporting of estimates, follow-up, events, and censoring; those numerical details are not reported in the registry record.
The design highlights why a treatment group’s observed outcomes are not equivalent to an estimate of comparative treatment effect. With no randomized control group, the study can describe outcomes in its participants but cannot use within-trial randomization to balance prognosis across treatment strategies. This distinction is important when reading reports from early-phase or single-group studies, especially when the stated objective concerns treatment activity.
The record also separates efficacy questions from safety summaries. Serious and other adverse event counts, event terms, and deaths can describe reported experience, but interpretation requires context about follow-up and attribution. In this case, the record gives selected counts without a concurrent comparator or full event-level context. The statistical lesson is to keep the endpoint, design, uncertainty, and reporting completeness in view together, and not infer more than the available estimates allow.
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 interpreting efficacy is that the registry record does not report the numerical result for freedom from progression at six months, despite specifying that the proportion and a 95% confidence interval would be reported. The record also does not give the median progression-free survival, survival estimates, response results, or numerical findings for the other listed outcomes. As a result, the study’s observed efficacy cannot be assessed from this information.
The single-group design has no concurrent comparator. It cannot provide a randomized estimate of how outcomes would differ under another treatment or no study treatment. Participant selection and disease course may influence outcomes, and the record does not quantify the role of such factors. Masking is listed as none; the record describes blinded central CT review for verification, but does not report its results or how it affected endpoint classification.
Important analysis details are also absent. The registry does not report the sample-size justification, complete analysis plan, multiplicity approach, analysis populations, missing-data strategy beyond censoring at last follow-up, or sensitivity analyses. Follow-up duration and event counts for the primary endpoint are not reported. The number of participants with incomplete assessments and reasons for any missing observations are also not reported in the registry record.
Safety interpretation is limited by the lack of event timing, attribution, and participant-level context in the listed figures, as well as the absence of a control group. The record describes both treatment until progression and treatment for as long as clinical benefit was derived; additional operational details are not reported. Biomarker sampling is mentioned, but biomarker findings are not included. These limitations restrict conclusions to the described design, endpoint definitions, and reported safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase II Study of Axitinib in Patients With Metastatic Renal Cell Cancer Unsuitable for Nephrectomy — NCT01693822.
- Registry record last updated 2024-11-21; status last verified 2024-11.
- Results first posted 2024-11-21.
- 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
NCT01693822 is a completed Phase II, single-group study of axitinib in people with clear-cell metastatic renal cell carcinoma considered unsuitable for nephrectomy. The record lists enrollment of 65, no allocation, and no masking. Axitinib is described as an oral tablet taken twice daily, with a starting dose of 5mg.
The primary endpoint is freedom from progression at six months, defined using death or confirmed progressive disease from study entry, with censoring at last follow-up for participants alive and progression free. A 95% confidence interval and Kaplan Meier progression-free survival analysis are described. The numerical primary endpoint result and other efficacy results are not reported in the registry record.
The record lists safety counts of 26 affected among 64 at risk for serious adverse events, 64 affected among 64 at risk for other adverse events, and 62 deaths. These figures do not establish causation or comparative risk. The single-group design and absence of reported efficacy estimates limit conclusions about treatment effects.