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 NEXT: Subsequent Exposure to Tyrosine Kinase Inhibition at Recurrence After Adjuvant Therapy in Renal Cell Carcinoma (NCT01649180), a na phase 2 study. The primary outcome is Progression-free Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01649180 |
| Phase | Phase 2 |
| Condition | Renal Cell Carcinoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | PrECOG, LLC. |
| Results posted | Yes |
2. Clinical Question
Population
Participants had renal cell carcinoma that had recurred or spread after initial surgery. Eligibility required prior participation in a clinical trial involving sunitinib, sorafenib, pazopanib, or placebo after surgery. The registry record describes the endpoint population as all participants. It does not give further eligibility details in the information recorded for this analysis.
Intervention
The study intervention was axitinib, an oral tyrosine kinase inhibitor. The arm description says treatment would continue until disease progression. The study examined axitinib in the first-line recurrent or metastatic setting after prior adjuvant therapy.
Comparator
There was no concurrent comparator arm. The study is recorded as single-group, with no allocation to separate study arms. Prior treatment history is part of the population definition; it is not a randomized comparison within this study.
Primary question
The primary endpoint was progression-free survival: the time from registration to disease progression or death, whichever occurred first. The clinical question was how long participants remained alive without recorded progression while receiving axitinib after prior adjuvant therapy. The endpoint was assessed every 12 weeks up to 36 months. Although this defines what the study set out to measure, the median progression-free survival and its 95% confidence interval are not reported in the registry record. Consequently, the record does not provide a numerical estimate of the primary outcome for this study.
3. Trial Design
This was a phase 2, single-group study sponsored by PrECOG, LLC. The registry record identifies axitinib as the intervention and describes oral treatment continuing until disease progression. It lists no allocation to a randomized comparison and no masking. The design therefore describes outcomes among participants receiving axitinib, rather than an estimate of the difference between axitinib and a concurrent control group.
The study concerned recurrent or metastatic renal cell carcinoma after initial surgery and prior participation in a clinical trial involving sunitinib, sorafenib, pazopanib, or placebo as adjuvant therapy. Its stated aim was to examine the effect of prior adjuvant tyrosine kinase inhibition on subsequent axitinib exposure in the first-line recurrent or metastatic setting. Because the study is single-group, any interpretation involving prior treatment history would require relevant outcome data and a suitable analysis; those details are not reported in the registry record.
The registry record gives enrollment as 3 and status as terminated. It lists a start of 2012-07 and primary completion of 2016-01. It does not report why the study was terminated or provide enough information to establish whether all enrolled participants completed the planned follow-up. The protocol’s sample-size justification, stopping rules, and any interim analyses are not reported in the registry record.
The primary endpoint was progression-free survival, assessed every 12 weeks up to 36 months. Secondary outcomes listed include overall response rate and biospecimen banking for IL-8 and VEGF-A, SNPs analysis, and tumor tissue. The registry record lists no primary outcome estimate or analysis results, so the study’s planned design can be described, but its primary endpoint findings cannot be quantified from this 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 | 3 |
| COMPLETED | 3 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: all participants
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.
| Characteristic | Unit | Axitinib |
|---|---|---|
| Participants analysed | 3 | |
| Age, Continuous | years | 54 (52 to 55) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 3 |
| 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 | 0 |
| Race (NIH/OMB): White | Participants | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival, measured over Assessed every 12 weeks up to 36 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 registration until the first of disease progression or death. It combines these events into a time-to-event outcome: a participant is counted as having reached the endpoint when either event occurs. In this study, progression was defined using RECIST v1.0 criteria, including a 20% increase in the sum of the longest diameters of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions.
This endpoint is used in clinical trials because it captures how long participants remain alive without documented worsening according to the stated disease criteria. It can incorporate both the timing and occurrence of events, rather than reducing follow-up to a simple count of participants with progression at a single time point. The registry record says assessment was scheduled every 12 weeks up to 36 months; the timing of assessments can therefore affect when progression is detected and recorded.
The planned summary was the median progression-free survival with a 95% confidence interval, for all participants. The median is a summary of the event-time distribution, while its confidence interval conveys uncertainty about the estimated median. Neither the median nor its confidence interval is reported in the registry record. The endpoint definition alone does not establish what outcomes occurred or how precisely they were estimated.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes a small, single-group phase 2 study of axitinib after prior adjuvant therapy for renal cell carcinoma. Enrollment was 3, and the registry status is terminated. Those design and enrollment details set the context for interpreting the record, but they do not provide an estimate of the primary endpoint.
Progression-free survival was the primary endpoint, defined from registration to progression or death, whichever occurred first. The planned summary was a median and 95% confidence interval. Neither is reported in the registry record. The record also does not provide participant-level event times, the number of progression or death events, or a description of censoring. Therefore, no account of the observed progression-free survival distribution or its precision can be drawn from the registry information.
The study has no concurrent comparator arm. Its outcomes, if reported, would describe participants treated with axitinib in this study; by themselves, they would not establish how outcomes differ from those under another treatment or from outcomes without axitinib. Prior adjuvant therapy is clinically relevant to the stated research question, but it does not function as a randomized control group. The registry record does not report a comparative analysis by prior therapy.
The enrollment count is especially important when considering precision. In general, estimates based on few participants can be highly uncertain, and time-to-event estimates depend on how many events occur and how follow-up is distributed. These are general statistical considerations, not additional findings about this study. The record does not report the number of endpoint events or the completeness of follow-up, so the uncertainty of the intended endpoint estimate cannot be assessed from the listed information.
Safety information is also limited. The record lists serious adverse events affecting 1 of 3 participants and other adverse events affecting 3 of 3 participants. Retinal vascular disorder is listed among the serious adverse event terms at 33.3%. These figures describe recorded events in this small group; they do not establish a comparative risk or characterize all possible harms. The record does not report deaths in the safety entry.
Overall, the registry record gives the study’s question, design, endpoint definition, enrollment, and selected safety counts, but not the primary outcome result. This distinction matters: a registered endpoint and a defined analysis do not substitute for the observed estimate. Statistical interpretation should remain limited to what the record actually reports.
9. Statistical Methods Explained
The study’s primary endpoint is a time-to-event outcome. Such outcomes record how long it takes for a defined event to occur, rather than only whether the event happened by a fixed visit. Here, the event is the first occurrence of disease progression or death after registration. The registry record defines progression using RECIST v1.0 and states that the endpoint was assessed every 12 weeks up to 36 months.
What does the median represent?
A median time-to-event estimate describes the point at which the estimated event-time distribution reaches its midpoint. It is not the average time for every participant, and it does not mean that all participants experience the event at that time. Participants whose event has not been observed by the end of their available follow-up can contribute information up to that point without being counted as having an event. This is commonly called censoring. The registry record does not report the censoring details or the number of events for this endpoint.
What does a confidence interval communicate?
A confidence interval expresses uncertainty around an estimated quantity, under the assumptions of the statistical method used. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. The intended summary was a median with a 95% confidence interval, but neither estimate is reported in the registry record. Without the estimate and interval, the precision of the primary endpoint cannot be evaluated.
Why can time-to-event estimates be uncertain?
In general, the information available for a time-to-event estimate depends not only on the number enrolled but also on the number and timing of events and on follow-up. A small group may yield few events, which can make an estimate unstable or imprecise. This is a general statistical point, not a calculation about the study. Enrollment was 3, but the number of progression or death events and the pattern of follow-up are not reported in the registry record.
What does the single-group design allow?
A single-group study can describe outcomes among the participants who received the intervention. It does not directly estimate a treatment contrast against a concurrent control group. Differences between participants with different treatment histories can reflect characteristics beyond treatment history, so a comparative conclusion would require a design and analysis that address those differences. The record lists no randomized comparison and does not report an analysis comparing prior adjuvant treatment groups.
The registry record notes no masking. In general, masking can reduce the influence of knowledge about assigned treatment on some aspects of trial conduct or assessment. Its relevance depends on the outcome and procedures. The record does not describe additional safeguards for outcome assessment, so these should not be inferred.
How should planning calculations be understood?
In general, sample-size planning calculations illustrate the amount of information that might be needed under stated assumptions. They are not observed results and do not show that a study had a particular probability of finding an effect. The planning assumptions recorded for illustrative calculations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a fraction of an observed effect. For time-to-event illustrations, the stated quantity is a total number of events. These are planning assumptions, not the design of this single-group study, and the record does not report the study’s own sample-size justification. No planning illustration should be read as observed power or as evidence that the primary endpoint result was statistically significant.
What is over-dispersion?
In general, over-dispersion occurs when observed variability in count data exceeds what a statistical model assumes. If unaccounted for, this can make uncertainty estimates too small. This concept may matter for some analyses of event counts, but the registry record does not report a statistical model for such an analysis. It should not be assumed that an over-dispersion adjustment was used.
The registry record lists no analysis results. It therefore does not identify the estimation procedure used for the primary endpoint, any statistical model for secondary outcomes, or whether any adjusted analyses were performed. The endpoint definition and the planned median summary explain what was intended to be measured, but the missing analysis details and outcome estimate limit independent statistical interpretation.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary endpoint, progression-free survival, and several secondary outcomes: overall response rate; biospecimen banking for IL-8 and VEGF-A; biospecimen banking for SNPs analysis; and tumor tissue banking. It also lists five outcome measures, but does not report analysis results. The statistical plan for handling multiple outcomes or multiple tests is not reported in the registry record.
In general, testing several hypotheses can increase the chance of observing at least one apparently notable result by chance. Statistical plans sometimes address this multiplicity through prespecified testing sequences or adjustment methods. No such approach is reported in the registry record, so it is not possible to determine whether or how multiplicity was handled. This limitation is particularly relevant to interpreting secondary analyses, if any were conducted.
The registry record identifies the primary endpoint population as all participants but does not report details about the analysis population, exclusions, or how participants with incomplete follow-up were treated. The number of endpoint events, censoring rules, and missing-data procedures are also not reported in the registry record. These details matter because the treatment of missing assessments and incomplete observation can affect time-to-event estimates and their uncertainty.
The record lists no analyses. It does not report whether the primary endpoint was analyzed according to a prespecified plan, whether analyses were conducted at interim points, or whether the analysis population differed from enrollment. These absences prevent assessment of the relationship between the intended analysis and any observed result. They should not be interpreted as evidence that a particular method was or was not used beyond what the registry record states.
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 | 1 | 3 | 33.3% |
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 |
|---|---|
| Axitinib | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | Axitinib |
|---|---|---|
| Retinal vascular disorder | Eye disorders | 1 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Axitinib |
|---|---|---|
| Hypertension | Vascular disorders | 3 of 3 |
| Fatigue | General disorders | 2 of 3 |
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | 2 of 3 |
| Anorexia | Metabolism and nutrition disorders | 1 of 3 |
| Pain in Extremity | Musculoskeletal and connective tissue disorders | 1 of 3 |
Serious events with the highest arm-level rate: retinal vascular disorder (33.3%).
The registry record lists serious adverse events for the axitinib group: 1 of 3 participants at risk was affected. It also lists other adverse events affecting 3 of 3 participants. These are counts within the enrolled group, not comparisons with another treatment group. Because the study has no concurrent comparator, the figures cannot estimate a difference in adverse-event frequency between treatments.
Retinal vascular disorder is listed among the top serious adverse event terms at 33.3%. This percentage is reported as recorded; it should be read alongside the small group size and the count of participants affected. A percentage based on a small group can change substantially with a single participant, so it should not be treated as a precise estimate of frequency in a broader population.
These registry entries do not describe event severity beyond the serious-event categorization, timing, duration, relationship to treatment, or whether events led to treatment discontinuation. The record does not report deaths in the safety entry. The listed counts are a limited account of recorded safety events, not a complete characterization of all potential adverse effects or a comparative safety assessment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase 2, single-group study evaluated oral axitinib for recurrent or metastatic renal cell carcinoma after prior adjuvant therapy. It defines progression-free survival as the primary endpoint and describes how progression was assessed. It also records enrollment of 3, termination status, and selected adverse-event counts. These registry entries describe the study and its recorded information.
The record does not report a median progression-free survival estimate or its 95% confidence interval. It therefore does not show how long participants remained alive without documented progression, nor how precise such an estimate would be. The absence of a reported estimate is not itself evidence that the intervention did or did not affect the endpoint.
Because there was no concurrent control group, any reported outcome from this design would describe the treated participants rather than establish a causal difference relative to another treatment. The study’s stated interest in prior adjuvant exposure does not remove this limitation. The registry record does not report comparative results by prior treatment history.
The safety entries show that serious adverse events were recorded in 1 of 3 participants and other adverse events in 3 of 3. The listed serious term retinal vascular disorder is reported at 33.3%. These counts are specific to the study group and do not provide a comparative risk estimate. Small enrollment also limits how precisely these observations can characterize a wider population.
Accordingly, the most defensible interpretation is descriptive: the registry record documents the study’s design, intended endpoint, enrollment, status, and selected safety information, but not the primary outcome result. No conclusion about treatment benefit, lack of benefit, or comparative safety can be drawn from the information recorded.
13. Why This Trial Matters Statistically
This study raises a statistical question about outcomes after prior adjuvant therapy: how to describe time to progression or death when participants later receive axitinib in the recurrent or metastatic setting. The endpoint definition makes explicit which events count and the time origin used. Clear definitions are essential for interpreting time-to-event results, because different event rules or time origins can lead to different quantities.
The single-group design also illustrates the distinction between describing an outcome and estimating a treatment effect. A cohort’s progression-free survival can be summarized, but without a concurrent comparator it does not by itself quantify how outcomes differ under another treatment. The study’s interest in prior therapy history is therefore not equivalent to a randomized comparison of those histories.
The registry record’s enrollment of 3 underscores why sample size and event information matter to precision. In time-to-event analysis, enrollment alone is not enough to assess the information available: the number and timing of events and the duration and completeness of follow-up also matter. Those event and follow-up details, as well as the primary estimate and confidence interval, are not reported in the registry record.
The contrast between a specified endpoint and an unreported endpoint result is another important statistical lesson. A registry can document what investigators intended to measure without supplying the estimate needed to judge its magnitude or uncertainty. The listed safety counts provide limited descriptive information, but cannot replace a comparative analysis or a fuller account of adverse events.
For readers assessing clinical evidence, this record is a reminder to separate protocol features, observed results, and causal interpretation. The design and endpoint are described, while the primary outcome analysis is not reported. That boundary determines what can be concluded statistically.
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.
Several limitations are specific to interpreting this study’s registry record. Enrollment was 3, and the study is recorded as terminated. The reason for termination and whether the planned follow-up was completed are not reported in the registry record. The record also does not report the number of progression or death events, participant-level follow-up, or censoring information. Without these details, the amount of information supporting the intended time-to-event estimate cannot be assessed.
The primary endpoint was specified, but its median and 95% confidence interval are not reported in the registry record. No primary analysis result is listed. The record does not state which statistical estimator or analysis procedures were used, whether the protocol’s intended analysis changed, or whether interim analyses occurred.
The single-group design has no concurrent control, limiting causal comparisons. The study’s question involves prior adjuvant exposure, but comparative outcomes by prior treatment history are not reported in the registry record. It also does not describe enough about participant characteristics or eligibility to assess how closely the enrolled group represents a broader population with recurrent or metastatic disease.
Safety information is limited to recorded counts and a listed serious adverse event term. Details such as timing, duration, treatment relationship, and outcomes of adverse events are not reported in the registry record. The analysis plan for secondary outcomes, multiplicity, missing observations, and analysis populations is also not reported. These limitations constrain interpretation of both efficacy and safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: NEXT: Subsequent Exposure to Tyrosine Kinase Inhibition at Recurrence After Adjuvant Therapy in Renal Cell Carcinoma — NCT01649180.
- Registry record last updated 2021-08-12; status last verified 2017-04.
- Results first posted 2017-04-20.
- 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 record describes NEXT, a phase 2, single-group study of oral axitinib for recurrent or metastatic renal cell carcinoma after prior adjuvant therapy. The intervention was to continue until disease progression. Enrollment was 3, and the study status is terminated.
The primary endpoint was progression-free survival from registration to progression or death, assessed every 12 weeks up to 36 months. The planned summary was a median with a 95% confidence interval, but the estimate and analysis results are not reported in the registry record.
The record lists serious adverse events affecting 1 of 3 participants, other adverse events affecting 3 of 3, and retinal vascular disorder at 33.3% among the top serious terms. These are descriptive counts without a concurrent control group. The record does not report the reason for termination or the primary endpoint result.