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 Linifanib in Treating Patients With Advanced, Refractory Colorectal Cancer (NCT01365910), a na phase 2 study. The primary outcome is Overall Response Rate (Complete Response + Partial Response) With a Target of at Least 15%.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01365910 |
| Phase | Phase 2 |
| Condition | Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IVA Colon Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 30 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Vanderbilt-Ingram Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced, refractory colorectal cancer expressing mutated kRas. The listed conditions include recurrent colon or rectal cancer and stage IVA or IVB colon or rectal cancer. The registry record reports enrollment of 30.
Intervention
Linifanib, taken by mouth once daily. Treatment courses were to repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Comparator
There was no comparator group: the study is recorded as single-group, with allocation listed as NA. It therefore does not provide a randomized or concurrent control comparison.
Primary question
The primary endpoint asks whether complete or partial tumor responses were observed under RECIST criteria. The stated target was an overall response rate of at least 15%. The registry record does not report the response rate or its confidence interval.
The question is about tumor response in a selected clinical population, not a comparison of linifanib with another treatment. The registry identifies the study as phase II and describes the patients as having advanced, refractory disease with mutated kRas. It lists response assessment from baseline and every 8 weeks, up to 2 years, and defines the response window as starting at treatment and ending at progression or recurrence.
Progression-free survival, overall survival, and worst-grade toxicity are listed as secondary outcomes. Their numerical results are not reported in the registry record. Consequently, the record supports describing the intended clinical question and its outcome framework, but it does not establish the observed magnitude or precision of response, survival, or toxicity outcomes.
3. Trial Design
The registry describes an investigator-initiated phase II study of linifanib in patients with advanced, refractory colorectal cancer expressing mutated kRas. It is recorded as a single-group study with allocation listed as NA and masking listed as none. Enrollment is reported as 30. The listed conditions cover recurrent colon and rectal cancer and stage IVA and IVB colon and rectal cancer.
Patients in the treatment group received linifanib by mouth once daily. Courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. This describes the intended treatment schedule; the registry record does not report individual treatment duration or treatment exposure.
The primary outcome is overall response rate, defined as complete response plus partial response. The stated target was at least 15%. Response was to be assessed at baseline and every 8 weeks, up to 2 years. Listed secondary outcomes are progression-free survival, overall survival, and the number of patients with each worst-grade toxicity.
The study began in 2011-06, had a primary completion date of 2012-05, and is recorded as terminated. The reason for termination is not reported in the registry record. These dates and status do not, by themselves, explain whether the study reached its planned endpoint assessments or why it ended.
Because the design has no control group, its results would describe outcomes observed among patients treated in this study; they would not estimate a randomized treatment contrast. The registry record does not report a detailed statistical analysis plan, an enrollment justification, or the reason for selecting the stated response target. It also does not report numerical primary efficacy results, although it lists four outcome measures and no analysis entries.
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.
Before assignment: Thirty-five patients consented to be on this study. Four patients were considered ineligible, and 1 patient withdrew prior to treatment.
Overall Study
| Stage | Treatment (Enzyme Inhibitor) |
|---|---|
| STARTED | 30 |
| COMPLETED | 0 |
| NOT COMPLETED | 30 |
Reasons for not completing this period:
| Reason | Treatment (Enzyme Inhibitor) |
|---|---|
| Withdrawal by Subject | 7 |
| disease progression | 18 |
| Adverse Event | 3 |
| other complicating disease | 1 |
| pt did not get tx, nausea/vomiting | 1 |
Analysis population for the primary outcome, as defined in the registry: All patients are included in the analysis on intention-to-treat basis. Analysis is by Kaplan-Meier method, where death is an event, with censoring for non-expired patients at greater of off-study date or last known alive date.
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 | Treatment (Enzyme Inhibitor) |
|---|---|---|
| Participants analysed | 30 | |
| Age, Customized: Age 20-29 | participants | 1 |
| Age, Customized: Age 40-49 | participants | 4 |
| Age, Customized: Age 50-59 | participants | 10 |
| Age, Customized: Age 60-69 | participants | 10 |
| Age, Customized: Age 70-79 | participants | 5 |
| Sex: Female, Male: Female | Participants | 14 |
| Sex: Female, Male: Male | Participants | 16 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| 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 | 24 |
| Race (NIH/OMB): More than one race | Participants | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 24 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 4 |
| Region of Enrollment: United States | participants | 30 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response Rate (Complete Response + Partial Response) With a Target of at Least 15%, measured over Baseline and every 8 weeks, up to 2 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of target lesions |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is overall response rate, defined as complete response plus partial response. In the registry description, complete response means disappearance of target lesions. Partial response means a decrease of more than 30% in the sum of the longest diameters of target lesions. The description also defines progressive disease as an increase of more than 20% in that sum or the appearance of new lesions; stable disease is neither a sufficient decrease nor increase. These definitions are attributed to RECIST criteria version 1.1.
Response rate is used to describe the proportion of patients who meet a prespecified tumor-response definition during the stated assessment period. It is a measure of tumor change, rather than a direct measure of how long patients live or how long they remain free of progression. The registry names progression-free survival and overall survival as secondary outcomes, which address different clinical questions.
The stated response target is at least 15%. The registry says response is recorded from the start of treatment until progression or recurrence, with assessments at baseline and every 8 weeks, up to 2 years. It also says exact two-sided 95% confidence intervals will be reported. However, the primary outcome’s listed unit is “percentage of target lesions,” while the outcome title calls it an overall response rate. The registry record does not clarify this distinction, and it does not report the observed response estimate or its confidence interval.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes the intent and design of a phase II study, but it does not give the numerical primary outcome. In particular, no observed overall response rate or confidence interval is reported. The stated target of at least 15% is a design or evaluation target, not an observed result. Without a reported estimate, it is not possible to determine from the registry record whether the target was met, how many patients had complete or partial responses, or how precise an estimate would have been.
The study is single-group and has no listed comparator. Any response observed in this group would therefore describe outcomes during treatment in the enrolled study population. It would not, by itself, separate a treatment effect from other explanations for tumor change or provide a randomized comparison with another treatment. The record’s allocation entry is NA, consistent with the absence of a comparative allocation.
The registry identifies several secondary outcomes: progression-free survival, overall survival, and the number of patients with each worst-grade toxicity. Their numerical results are not reported in the registry record. The record also lists four outcome measures but no analysis entries. Thus, the posted information does not support an interpretation of survival estimates, response timing, or the distribution of toxicity grades.
The primary outcome description contains a methodological ambiguity. Its title identifies overall response rate, while its unit is described as percentage of target lesions. The accompanying population description refers to a Kaplan-Meier method, death as an event, and censoring of non-expired patients at the greater of the off-study date or last known alive date. That wording is characteristic of a time-to-event analysis, but the registry does not explain how it applies to the response-rate endpoint. The record therefore does not make the primary analysis method clear.
The adverse-event record does report counts for the treatment group: 16 of 30 participants are listed as affected by serious adverse events, and 29 of 30 by other adverse events. These are distinct categories in the record and should not be combined. Serious adverse event terms and percentages are also listed, but the record does not provide a treatment-versus-control comparison or enough context to attribute an event to linifanib. The safety information is descriptive.
The trial is recorded as terminated, but the reason is not reported in the registry record. Termination status alone does not reveal whether the planned response assessments were completed or why the trial ended. The record also does not report the planned sample-size justification or explain whether recruitment, follow-up, or analysis differed from the original intentions. Interpretation should therefore remain limited to the stated design, outcome definitions, and posted safety counts, without treating absent efficacy estimates as evidence for or against an effect.
9. Statistical Methods Explained
The registry describes a single-group phase II study. In a single-group design, outcomes are assessed among participants receiving the study treatment, without a concurrent comparison group. This can describe what happened in the studied group, but it does not directly estimate the difference between treatments. In this study, allocation is listed as NA and masking as none. The record does not describe a randomized allocation process or a blinded assessment process.
What does the response-rate endpoint represent?
Overall response rate combines complete and partial responses according to the stated RECIST criteria. The criteria translate changes in measurable target lesions into response categories. Complete response is disappearance of target lesions; partial response is a decrease of more than 30% in their summed longest diameters. Progressive disease is an increase of more than 20% in that sum or new lesions, while stable disease meets neither the response nor progression description. These categories provide a standardized way to classify tumor change, although the registry record does not provide the observed category counts.
The title of the primary outcome specifies complete response plus partial response and gives a target of at least 15%. That target is not a reported response estimate. The registry also lists the endpoint unit as percentage of target lesions. Because that wording differs from the usual patient-level description implied by “overall response rate,” the exact calculation unit is not clear from the record. The endpoint description says exact two-sided 95% confidence intervals will be reported, but no interval is posted.
How should a confidence interval be understood?
In general, a confidence interval expresses the uncertainty around an estimate under a specified statistical procedure. A narrower interval indicates greater precision under that procedure; a wider interval indicates more uncertainty. It does not guarantee that the estimate is free of bias, and it does not resolve limitations caused by the design or by missing information. Here, the registry states that an exact two-sided 95% interval is planned for the primary response outcome, but it does not report either the estimate or interval. There is consequently no basis in the registry record for judging the response estimate’s precision.
What does the record say about time-to-event methods?
The population description says the analysis is by Kaplan-Meier method, with death as an event and censoring for non-expired patients at the greater of off-study date or last known alive date. In general, Kaplan-Meier methods estimate the distribution of time until an event while accommodating participants whose event time is not observed during follow-up through censoring. Censoring uses their observed follow-up without treating them as having had the event. The validity of such estimates depends on assumptions about follow-up and censoring.
That method description does not clearly match the primary outcome title, which is response rate, rather than a time-to-event endpoint. The registry does not explain whether the Kaplan-Meier wording applies to a secondary outcome, how it relates to response, or whether the analysis description was updated. The stated secondary outcomes include progression-free survival and overall survival, for which time-to-event methods may be relevant in general, but the record does not give their analysis details or estimates. This is an ambiguity in the registry description, not a basis for inferring an unreported method.
How should safety counts be interpreted?
The adverse-event record distinguishes serious adverse events from other adverse events. It reports the number at risk and affected in each category for the treatment group. These counts describe what is recorded in the registry; they do not indicate comparative risk because there is no control group. The record lists selected serious adverse event terms with percentages, but it does not provide definitions of attribution or a complete account of how events were collected. General interpretation of adverse-event frequencies should consider the observation period and ascertainment process, neither of which is fully detailed in the posted safety summary.
What is absent from the statistical description?
The registry does not report a detailed statistical analysis plan, an explanation of the sample-size justification, or an approach to multiplicity across outcomes. It lists four outcome measures and no analysis entries. It also does not report a missing-data strategy for response assessments. The primary description says all patients are included on an intention-to-treat basis, but it does not explain how participants without an evaluable response assessment are classified. Those omissions limit reproducibility and make it difficult to assess whether the stated analysis methods were followed.
General planning calculations based on an observed effect, if presented separately, are illustrations under assumptions rather than evidence that the original study had that power. The record describes planning assumptions involving a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions do not describe this single-group trial’s design, and the registry does not report that they were its own design calculations. Planning illustrations are not observed power and do not substitute for reported results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists overall response rate as the primary outcome and progression-free survival, overall survival, and the number of patients with each worst-grade toxicity as secondary outcomes. It reports four outcome measures and no analysis entries. A strategy for handling multiplicity across outcomes is not reported in the registry record. Without such a strategy, the posted information does not establish how any multiple statistical tests or outcome assessments were intended to affect interpretation.
The primary outcome description states that all patients are included in the analysis on an intention-to-treat basis. This identifies the intended analysis population, but the record does not explain how patients without a response assessment would be handled or whether any participants were excluded from a particular analysis. A method for handling missing response data is not reported in the registry record. Nor does the record provide details on missingness in the secondary outcomes.
The description also mentions Kaplan-Meier analysis, death as an event, and censoring non-expired patients at the greater of the off-study date or last known alive date. It does not make clear which outcome this procedure applies to. The stated rule offers some information about censoring for a time-to-event analysis, but does not explain how censoring, loss to follow-up, or incomplete assessment would be addressed for the primary response endpoint.
The absence of analysis entries means that planned methods and numerical estimates cannot be checked against posted analyses. The reason the trial was terminated is not reported in the registry record, and the record does not indicate whether termination affected assessment completion or analysis populations.
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 (Enzyme Inhibitor) | 16 | 30 | 53.3% |
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 |
|---|---|
| Treatment (Enzyme Inhibitor) | 29 of 30 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment (Enzyme Inhibitor) |
|---|---|---|
| General disorders and administration site conditions Pain | General disorders | 3 of 30 |
| Urinary tract infection | Infections and infestations | 3 of 30 |
| dehydration | Metabolism and nutrition disorders | 3 of 30 |
| diarrhea | Gastrointestinal disorders | 2 of 30 |
| nausea | Gastrointestinal disorders | 2 of 30 |
| Vomiting | Gastrointestinal disorders | 2 of 30 |
| Abdominal pain | Gastrointestinal disorders | 1 of 30 |
| Ascites | Gastrointestinal disorders | 1 of 30 |
| colonic obstruction | Gastrointestinal disorders | 1 of 30 |
| constipation | Gastrointestinal disorders | 1 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Enzyme Inhibitor) |
|---|---|---|
| fatigue | General disorders | 24 of 30 |
| hypertension | Vascular disorders | 20 of 30 |
| anemia | Blood and lymphatic system disorders | 20 of 30 |
| proteinuria | Renal and urinary disorders | 18 of 30 |
| diarrhea | Gastrointestinal disorders | 17 of 30 |
| abdominal pain | Gastrointestinal disorders | 15 of 30 |
| nausea | Gastrointestinal disorders | 15 of 30 |
| alkaline phosphatase increased | Investigations | 15 of 30 |
| aspartate aminotransferase increased | Investigations | 15 of 30 |
| anexoria | Metabolism and nutrition disorders | 14 of 30 |
Serious events with the highest arm-level rate: general disorders and administration site conditions pain (10.0%), urinary tract infection (10.0%), dehydration (10.0%), diarrhea (6.7%), nausea (6.7%).
The registry reports serious adverse events and other adverse events separately for the treatment group. For serious adverse events, 30 participants are listed at risk and 16 as affected. For other adverse events, 30 are listed at risk and 29 as affected. These are registry counts, not a comparison between linifanib and another treatment, because the study has no control group.
The record lists these serious adverse event terms with percentages: General disorders and administration site conditions Pain, 10.0%; urinary tract infection, 10.0%; dehydration, 10.0%; diarrhea, 6.7%; nausea, 6.7%; and vomiting, 6.7%. These entries describe the reported serious-event terms. They should not be read as proof that linifanib caused each event or as a complete account of all safety findings. The record does not report the event-attribution process, exposure-adjusted rates, or a comparative safety analysis.
“At risk” and “affected” describe the counts recorded for these categories; the registry summary does not provide enough detail to infer event duration, recurrence, or the timing of events. It also does not report numerical worst-grade toxicity results, although that outcome is listed as secondary.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase II, single-group study of linifanib was conducted in patients described as having advanced, refractory colorectal cancer expressing mutated kRas. It states the intended dosing schedule, primary response endpoint, response criteria, and secondary outcomes. It also reports selected adverse-event counts and serious-event terms. These registry entries characterize the study, but they do not supply a numerical primary efficacy result.
The registry’s target of at least 15% is not evidence that the observed response rate reached that level. The response estimate and its confidence interval are not reported in the registry record. As a result, the record does not show how many complete or partial responses occurred, whether the target was met, or how precisely response was estimated. Numerical results for progression-free survival and overall survival are also not reported.
The safety entries are descriptive observations in a group receiving linifanib. Without a control group, they cannot establish how the event frequency compares with another treatment or with a counterfactual outcome. The record also does not provide enough information to determine whether the listed events were judged related to treatment. A list of events and affected counts is not, by itself, a causal assessment.
The single-group design cannot provide the protection against confounding that a randomized comparison is intended to offer. Any observed outcome in the group could reflect multiple influences, and the registry does not offer a comparative estimate that would isolate the contribution of linifanib. This does not negate the descriptive value of a phase II study, but it sets limits on what can be inferred.
The registry’s statistical description is incomplete and includes an unexplained reference to Kaplan-Meier analysis in connection with the primary outcome. The reason for termination, missing-data procedures, and detailed analysis plan are not reported. Accordingly, the most defensible reading is that the record documents the design and some safety observations while leaving the central efficacy result and several analytic details unavailable. It does not establish that linifanib works or does not work.
13. Why This Trial Matters Statistically
This trial is statistically notable for the gap between a clearly stated response target and the absence of a posted response estimate. A target of at least 15% gives the endpoint a benchmark, but interpreting a study against that benchmark requires the observed response rate and its uncertainty. Neither is reported in the registry record. The design and endpoint description alone cannot answer whether the benchmark was reached.
The single-group structure is also central to interpretation. It can provide descriptive information about outcomes in the treated study population, but it does not estimate a randomized comparison. The distinction matters because an outcome observed during treatment is not the same quantity as a treatment effect relative to a control condition. The study’s phase II designation does not remove this limitation.
There is also a reporting issue in the primary outcome description. Overall response rate is named as the endpoint, yet the listed unit is percentage of target lesions, and the population description refers to Kaplan-Meier analysis with death as an event and censoring. The registry does not explain how these elements fit together. Clear alignment among endpoint, analysis population, estimand, and statistical method is important for reproducibility and for understanding what an estimate would mean.
The registry additionally lists survival and toxicity outcomes but does not post numerical analyses for them. The stated termination status, without a reported reason or results, leaves questions about the completeness of planned follow-up and analysis unanswered. Taken together, these features make the record useful for understanding the intended study question, while limiting what can be concluded about efficacy, precision, and comparative safety.
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 principal limitation in interpreting this particular registry record is that the primary response estimate and its confidence interval are not reported. The stated target of at least 15% cannot substitute for the observed endpoint. Numerical results for the listed secondary outcomes are also not reported, and the registry lists no analysis entries.
The study is recorded as single-group, with allocation listed as NA and masking as none. There is no concurrent comparator in the registry description, so comparative treatment effects cannot be estimated from this design alone. The record does not detail how response assessments were adjudicated or whether assessors were independent of treatment knowledge.
The endpoint description is not fully consistent: it names overall response rate, lists “percentage of target lesions” as the unit, and includes a Kaplan-Meier analysis description involving death and censoring. The registry record does not clarify how these descriptions relate. It also does not report the statistical analysis plan, the rationale for the response target, or the sample-size justification.
Missing-data handling for the response endpoint is not reported in the registry record. Although the description says the analysis includes all patients on an intention-to-treat basis, it does not say how participants lacking an evaluable assessment would be treated. Details about follow-up completeness and analysis populations for secondary outcomes are also not reported.
The reason for termination is not reported in the registry record. Without that information or posted outcome analyses, the record does not establish whether termination affected recruitment, follow-up, or endpoint completion. The safety summary is limited to reported counts and selected serious-event terms; the registry does not provide a comparative safety analysis or all details needed to assess event attribution and timing.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Linifanib in Treating Patients With Advanced, Refractory Colorectal Cancer — NCT01365910.
- Registry record last updated 2014-08-26; status last verified 2014-08.
- Results first posted 2014-08-26.
- 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 phase II, single-group study of linifanib in patients with advanced, refractory colorectal cancer expressing mutated kRas. Enrollment is reported as 30, and the study is recorded as terminated. Patients were to receive linifanib by mouth once daily in repeating 28-day courses, absent progression or unacceptable toxicity.
The primary endpoint is overall response rate, defined as complete response plus partial response, with a stated target of at least 15%. Response assessments were planned at baseline and every 8 weeks, up to 2 years. The registry lists progression-free survival, overall survival, and worst-grade toxicity as secondary outcomes.
The registry record does not report a numerical primary response result, its confidence interval, or numerical analyses of the secondary outcomes. It reports serious adverse events affecting 16 of 30 participants and other adverse events affecting 29 of 30. The reason for termination and the detailed statistical analysis plan are not reported in the registry record.