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 Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma (NCT01030783), a randomized phase 3 study. The primary outcome is Progression-free Survival (PFS) of Subjects With Advanced Renal Cell Cancer (RCC) Randomized to Treatment With Tivozanib or Sorafenib.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01030783 |
| Phase | Phase 3 |
| Condition | Advanced Renal Cell Carcinoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 517 |
| Arms in the primary outcome | 2 |
| Lead sponsor | AVEO Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
The trial enrolled subjects with advanced renal cell carcinoma. The primary outcome was defined for the intention-to-treat population, meaning the registry identifies the randomized population as the basis for that outcome. The record does not give further eligibility details in the information summarized for this comparison.
Intervention
The experimental arm received tivozanib (AV-951). The registry identifies the drug but does not report the dosing schedule or other treatment-delivery details in the information. The trial was open-label, so masking was not used.
Comparator
The comparison arm received sorafenib. Both arms were part of a randomized, controlled, parallel-arm study. The registry lists 260 participants in the tivozanib arm and 257 in the sorafenib arm for the primary endpoint.
Primary question
The primary question was whether progression-free survival differed between participants randomized to tivozanib and those randomized to sorafenib. Progression-free survival was measured from randomization until documented disease progression or death from any cause, whichever came first. The posted primary results are arm-specific median times with 95% confidence intervals. A sponsor-reported hazard ratio or formal between-arm test is not reported in the registry record, so the posted medians alone do not provide a complete inferential comparison.
3. Trial Design
This was a phase 3, randomized, controlled, multinational, multicenter, open-label, parallel-arm trial comparing tivozanib (AV-951) with sorafenib in subjects with advanced renal cell carcinoma. The registry records enrollment of 517 participants. For the primary endpoint, 260 participants are listed in the tivozanib arm and 257 in the sorafenib arm. The primary outcome population is identified as the intention-to-treat population.
The registry gives a start date of 2009-12 and a primary completion date of 2012-07, and lists the study status as completed. AVEO Pharmaceuticals, Inc. is identified as the sponsor. The trial planned to compare progression-free survival as its primary outcome, alongside overall survival, objective response rate, duration of response, safety and tolerability, kidney-specific symptoms and health outcomes, and tivozanib pharmacokinetics.
Open-label means participants and study personnel were not masked to the assigned treatment, according to the registry's masking classification. Random allocation supports a planned comparison between groups, but the record does not describe the randomization procedure or allocation concealment. It also does not report treatment doses, schedules, adherence, crossover, or subsequent treatments in the information summarized for these outcomes. Those details should not be inferred from the trial title or general knowledge about the drugs.
The registry lists two treatment arms and a parallel design. It does not report a detailed protocol description, the planned sample-size justification, or a statistical analysis plan. It also does not list sponsor-reported comparative analyses in the posted results. These absences limit how fully the design and the intended inferential approach can be reconstructed from the registry record alone.
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 | Tivozanib (AV-951) | Sorafenib |
|---|---|---|
| STARTED | 260 | 257 |
| COMPLETED | 211 | 231 |
| NOT COMPLETED | 49 | 26 |
Analysis population for the primary outcome, as defined in the registry: ITT Population
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: All randomized subjects
| Characteristic | Unit | Tivozanib (AV-951) | Sorafenib | Total |
|---|---|---|---|---|
| Participants analysed | 260 | 257 | 517 | |
| Age, Continuous | Years | 59 (23 to 83) | 59 (23 to 85) | 59 (23 to 85) |
| Sex: Female, Male: Female | Participants | 75 | 68 | 143 |
| Sex: Female, Male: Male | Participants | 185 | 189 | 374 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival (PFS) of Subjects With Advanced Renal Cell Cancer (RCC) Randomized to Treatment With Tivozanib or Sorafenib, measured over From date of randomization until the date of first documented progression or date of death from any cause, whichever came first. Disease progression was assessed every 8 weeks..
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint was progression-free survival, measured in months. For each participant, the interval began at randomization and ended at the first documented tumor progression or death from any cause, whichever occurred first. Disease progression was assessed every 8 weeks. The registry describes progression using RECIST 1.0 criteria: an 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.
The reported summary is the median progression-free survival for each arm, accompanied by a 95% confidence interval. In general, a median time-to-event value is the point at which an estimated event-free proportion reaches one half; it describes the middle of the event-time distribution rather than the experience of every participant. The confidence interval conveys uncertainty around the estimated median.
Progression-free survival is used in clinical trials because it captures time until progression or death, rather than only whether an event occurred by a single fixed assessment time. It does not by itself establish how the full event-time distributions compare. A hazard ratio, an appropriate confidence interval, or another sponsor-reported between-arm analysis would help quantify that comparison; such a result is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary endpoint results are median progression-free survival of 11.9 months for tivozanib, with a 95% confidence interval of 9.3 to 14.7 months, and 9.1 months for sorafenib, with a 95% confidence interval of 7.3 to 9.5 months. These are arm-specific summaries for the intention-to-treat population. The observed median is numerically higher in the tivozanib arm, but the medians alone do not quantify the relative event rate over follow-up or establish the strength of evidence for a between-arm difference.
The confidence intervals describe uncertainty around each arm's median estimate. They are not a direct confidence interval for the difference between arms. Comparing the endpoints of two separate intervals is not a substitute for a formal comparative analysis. The registry record does not report a hazard ratio, confidence interval for a hazard ratio, log-rank test, or other sponsor-reported primary comparison. It therefore does not support a statement about the statistical significance of the primary endpoint based on sponsor analysis.
The outcome was defined as time to progression or death, whichever occurred first, and disease progression was assessed every 8 weeks. Thus, the event-time endpoint combines two types of event and depends on the timing and ascertainment of progression. The registry record does not describe censoring rules, handling of missed assessments, or the number of events contributing to the analysis. Those details matter when interpreting a time-to-event result.
The arm sizes listed for the primary outcome are 260 and 257. The similar allocation is consistent with the randomized parallel-arm design, but arm size alone does not determine precision: the amount and timing of observed follow-up and events also matter. Those data are not reported in the registry record.
Because the record lists no sponsor-reported analyses, the primary medians should be read as descriptive posted results rather than a complete inferential comparison. They characterize the recorded outcomes in the two randomized arms, but do not by themselves show whether any observed separation could plausibly reflect sampling variation or how the relative event experience changed over time.
9. Statistical Methods Explained
Progression-free survival is a time-to-event endpoint. Each participant contributes time from randomization until progression or death, if one of those events is recorded. Participants without a recorded event by the end of their observed follow-up are generally treated as censored in time-to-event methods. Censoring is not the same as an event: it indicates that the event time is not known beyond the last relevant observation. The registry record does not report the censoring rules or explain how incomplete follow-up was handled.
What does the median describe?
The median is a summary of the estimated event-time distribution. In general, it marks the time by which half of the estimated population has experienced the event, under the analysis method used. The posted medians are 11.9 months for tivozanib and 9.1 months for sorafenib. A median focuses on one point in the distribution. It does not show whether the two arms had similar or different event patterns throughout follow-up, and it does not describe the experience of each participant.
Time-to-event analysis commonly uses an estimated survival curve to account for participants with different follow-up lengths and censored observations. A hazard ratio can summarize the relative event rate over time under assumptions of the chosen model. Neither an analysis method for the posted medians nor a sponsor-reported hazard ratio is included in the registry results. The registry record therefore does not establish which comparative model was used for the primary endpoint.
How should the confidence intervals be read?
The 95% confidence interval gives a range of values compatible with the observed data under the method and assumptions used to calculate it. The primary interval is 9.3 to 14.7 months for tivozanib, and 7.3 to 9.5 months for sorafenib. These intervals relate separately to each arm's median. They are not a confidence interval for the difference between medians, nor do they directly test whether the arms differ. A formal comparative estimate with its uncertainty is needed for that purpose.
In general, confidence intervals reflect sampling uncertainty, not every source of uncertainty. They do not automatically account for limitations such as missing outcome assessments, deviations from the analysis plan, or unmeasured differences in care after randomization. The registry does not report enough detail to assess those issues for this endpoint.
What does the intention-to-treat population mean?
The registry identifies the primary population as intention-to-treat. In general, intention-to-treat analysis groups participants according to randomized assignment, regardless of later treatment changes, and aims to preserve the advantages of randomization. The record does not describe how participants with missing or unavailable outcome data were handled, or whether the analysis included every randomized participant as assigned. The endpoint arm counts listed are 260 and 257, but those counts do not by themselves establish the full analysis procedures.
Why are time-to-event details important?
Progression was assessed every 8 weeks. This schedule means the date progression is documented may not be the exact date biological progression began. The registry specifies that the endpoint runs to first documented progression or death, but does not explain how assessment timing, missed visits, or deaths occurring without a recent tumor assessment were handled. The definition of progression refers to RECIST 1.0 criteria, including changes in target and non-target lesions and new lesions.
In general, time-to-event precision depends on the number and timing of events as well as the number enrolled. A larger number of events can provide more information about the event-time comparison, while censoring and unequal follow-up can affect precision. The registry does not report the primary event count or follow-up distribution in the outcome details. Enrollment of 517 participants cannot substitute for those quantities.
No multiplicity plan, interim monitoring approach, or sample-size justification for the primary endpoint is reported in the registry record. These omissions make it impossible to determine from the registry alone whether the posted primary estimate corresponds to a prespecified analysis, whether any adjustment was planned for multiple comparisons, or what assumptions informed trial planning. The registry also does not report a sponsor analysis of the primary between-arm contrast. The posted median estimates remain interpretable as arm-level summaries, but the missing analysis details limit conclusions about comparative uncertainty.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a statistical analysis plan describing how multiple outcomes or comparisons were to be handled. The trial lists a primary endpoint and several secondary outcomes, including overall survival, response, duration of response, safety, kidney-specific health outcomes, and pharmacokinetics. Testing or estimating many outcomes creates a multiplicity issue: in general, the chance of observing at least one apparently unusual result can increase as the number of comparisons grows. A prespecified hierarchy or adjustment can help control interpretation, but none is reported in the registry record.
The record does not report whether interim analyses were planned or performed, whether any stopping rules were used, or what significance threshold was specified for the primary comparison. The sample-size justification is also not reported. These omissions prevent assessment of how the trial's design related to its planned precision and inferential claims.
The primary population is identified as the intention-to-treat population. However, the record does not describe the handling of missing outcome assessments, loss to follow-up, censoring, protocol deviations, or participants who stopped or changed treatment. For progression-free survival, these details can affect how event times and censored observations are represented. The record specifies progression assessment every 8 weeks, but does not describe how missed or delayed assessments were handled.
For secondary outcomes, the registry does not provide analysis populations or missing-data procedures in the information. The posted objective response estimates use arm counts, but those counts do not explain how unavailable assessments were classified. No sponsor-reported analyses are listed. The available record therefore gives some outcome summaries but does not provide enough methodological detail to verify the treatment of multiplicity, missingness, or analysis populations across outcomes.
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 |
|---|---|---|---|
| Tivozanib (AV-951) | 74 | 259 | 28.6% |
| Sorafenib | 56 | 257 | 21.8% |
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 |
|---|---|
| Tivozanib (AV-951) | 238 of 259 |
| Sorafenib | 249 of 257 |
Most frequent serious adverse event terms
| Event term | Organ system | Tivozanib (AV-951) | Sorafenib |
|---|---|---|---|
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 9 of 259 | 2 of 257 |
| Anaemia | Blood and lymphatic system disorders | 4 of 259 | 4 of 257 |
| Cerebrovascular accident | Nervous system disorders | 4 of 259 | 3 of 257 |
| Myocardial infarction | Cardiac disorders | 2 of 259 | 4 of 257 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 3 of 259 | 2 of 257 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 2 of 259 | 3 of 257 |
| Hypertension | Vascular disorders | 3 of 259 | 2 of 257 |
| Acute myocardial infarction | Cardiac disorders | 2 of 259 | 2 of 257 |
| Fatigue | General disorders | 3 of 259 | 1 of 257 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 0 of 259 | 4 of 257 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tivozanib (AV-951) | Sorafenib |
|---|---|---|---|
| Hypertension | Vascular disorders | 116 of 259 | 91 of 257 |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | 36 of 259 | 139 of 257 |
| Diarrhoea | Gastrointestinal disorders | 63 of 259 | 85 of 257 |
| Weight decreased | Investigations | 49 of 259 | 54 of 257 |
| Fatigue | General disorders | 53 of 259 | 41 of 257 |
| Asthenia | General disorders | 44 of 259 | 44 of 257 |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | 55 of 259 | 12 of 257 |
| Alopecia | Skin and subcutaneous tissue disorders | 6 of 259 | 55 of 257 |
| Back pain | Musculoskeletal and connective tissue disorders | 38 of 259 | 21 of 257 |
| Nausea | Gastrointestinal disorders | 34 of 259 | 19 of 257 |
Serious events with the highest arm-level rate: neoplasm progression (3.5%), myocardial infarction (1.6%), pleural effusion (1.6%), anaemia (1.6%), cerebrovascular accident (1.5%).
The registry lists serious adverse events for 74 of 259 participants at risk in the tivozanib group and 56 of 257 at risk in the sorafenib group. It also lists other adverse events for 238 of 259 and 249 of 257 participants, respectively. These are counts of participants recorded as affected, not measures of event severity across all possible outcomes or of comparative risk adjusted for follow-up.
The listed serious adverse event terms include neoplasm progression at 3.5%, myocardial infarction at 1.6%, pleural effusion at 1.6%, anaemia at 1.6%, cerebrovascular accident at 1.5%, and dyspnoea at 1.2%. The registry listing does not specify an arm for these term percentages in the information, so they should not be assigned to either treatment group. Death counts are not reported in the registry record.
In general, adverse-event summaries depend on definitions, observation time, attribution practices, and completeness of reporting. The record does not provide those details here, and the raw counts should not be treated as a formal between-arm safety comparison.
12. What the Result Does, and Does Not, Mean
The posted primary results describe median time without documented progression or death in the two randomized groups. The median was 11.9 months in the tivozanib arm and 9.1 months in the sorafenib arm. Each estimate has a 95% confidence interval, reflecting uncertainty around that arm's median. The numerical pattern is descriptive; the registry does not report a sponsor-reported hazard ratio or formal primary comparison to quantify the evidence for a between-arm difference.
These results do not mean that every participant experienced the median duration, and they do not describe what happened to every participant after progression or censoring. A median is one summary of a time-to-event distribution. It does not reveal the shape of the full event-time curves, the relative event rates across follow-up, or differences in outcomes not captured by progression-free survival.
The trial was randomized, which is intended to support a fair comparison of assigned groups, but it was open-label. The registry record also lacks details about censoring, missing assessments, treatment delivery, and the primary comparative analysis. Those limits matter when moving from arm-level summaries to an interpretation of the treatment contrast.
The results should not be read as medical advice or as a guarantee of an individual outcome. Nor do the available registry summaries establish a definitive overall assessment of benefits and harms: the record contains a limited set of secondary results and does not report a complete sponsor analysis. A fuller interpretation would require the prespecified analysis, follow-up and event details, and complete results for relevant outcomes.
13. Why This Trial Matters Statistically
This trial illustrates why a randomized comparison is more than a comparison of two arm-level medians. Progression-free survival is a time-to-event outcome, and its interpretation depends on event timing, censoring, follow-up, and the statistical method used to compare groups. The registry reports median estimates and confidence intervals, but not the sponsor-reported hazard ratio or another formal comparison. That distinction separates descriptive summaries from a quantified treatment contrast.
The record also shows the importance of distinguishing endpoint-specific results from broader conclusions. The trial planned to evaluate multiple outcomes, including survival, response, safety, symptoms, health outcomes, and pharmacokinetics. These outcomes capture different questions. Without a reported multiplicity strategy and sponsor analyses, secondary findings require cautious interpretation and cannot be treated as a single body of confirmatory evidence.
For biostatistical interpretation, the missing details are consequential: the registry does not report the primary event count, censoring procedures, missing-data handling, interim analyses, or sample-size justification. Each can affect the precision and meaning of a time-to-event comparison. The posted record is therefore useful for identifying the trial structure and the reported arm summaries, while also demonstrating why complete analysis documentation matters.
The central statistical lesson is to match the strength of a claim to the evidence actually reported. Arm-specific medians and confidence intervals describe the observed summaries; they do not replace a comparative estimate with its uncertainty. Similarly, unadjusted secondary results can add exploratory context but do not automatically support confirmatory claims when many outcomes are considered.
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 trial from its registry record. The primary endpoint is summarized by arm-specific medians and confidence intervals, but a sponsor-reported hazard ratio, confidence interval for the between-arm effect, and formal test are not reported. The primary event count and follow-up distribution are also not reported, limiting assessment of time-to-event precision.
The record identifies progression assessment every 8 weeks and gives a RECIST 1.0-based progression definition, but does not explain how missed assessments, progression dates between visits, or censoring were handled. It does not describe the treatment of participants who discontinued assigned therapy, received subsequent treatment, or had incomplete outcome data. Those details are relevant to interpretation of progression-free survival and other outcomes.
The trial was open-label, and masking was recorded as none. The registry record does not describe any procedures that may have reduced bias in outcome assessment. It does not report treatment schedules or adherence details in the information summarized for these results. No protocol-level analysis plan, sample-size justification, multiplicity approach, or interim analysis details are reported.
Secondary outcome reporting is limited: the registry lists the planned outcome areas, but does not report numerical results for several of them in the information. Serious adverse event term percentages are listed without an arm assignment in the available details, and death counts are not reported. These gaps mean that the record alone cannot support a comprehensive comparison across all planned outcomes or a complete safety interpretation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma — NCT01030783.
- Registry record last updated 2019-10-28; status last verified 2019-10.
- Results first posted 2019-10-28.
- 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
NCT01030783 is a completed phase 3 randomized, controlled, multinational, multicenter, open-label, parallel-arm trial of tivozanib (AV-951) versus sorafenib in subjects with advanced renal cell carcinoma. The registry lists enrollment of 517, with a start date of 2009-12 and primary completion date of 2012-07.
The primary endpoint was progression-free survival in the intention-to-treat population, measured from randomization until documented progression or death. The posted median was 11.9 months for tivozanib and 9.1 months for sorafenib, with arm-specific 95% confidence intervals. A sponsor-reported comparative hazard ratio or formal primary analysis is not reported in the registry record.
Planned secondary outcomes included overall survival, objective response, duration of response, safety and tolerability, kidney-specific symptoms and health outcomes, and pharmacokinetics. Analysis-plan details, missing-data procedures, multiplicity handling, and the sample-size justification are not reported in the registry record.