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 Study of JI-101 in Patients With Advanced Low Grade Endocrine Tumors, Ovarian Cancers or K-RAS Mutant Colon Cancers (NCT01149434), a non-randomized phase 1, phase 2 study. The primary outcome is Effect of JI 101 on Pharmacokinetics Area Under Curve (AUC) (0-inf) of RAD001.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01149434 |
| Phase | Phase 1, Phase 2 |
| Condition | Cancer, Neuroendocrine, Ovarian Cancer |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 19 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Utah |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled patients with advanced solid tumors. Its pharmacodynamic part focused on three groups: patients with advanced low grade endocrine tumors, ovarian cancers, or K-RAS mutant colon cancers. The registry lists an enrollment of 19 across the study; it does not report how many participants in each disease group completed treatment or contributed to each outcome.
Intervention
The pharmacodynamic arm received JI-101 alone, as oral capsules at 200 mg twice daily in 28 day treatment cycles. The pharmacokinetic arm included four patients and used JI-101 with everolimus. That part examined everolimus exposure when given alone and in the presence of JI-101.
Comparator
There was no randomized control group. In the pharmacokinetic assessment, the record describes measurements of everolimus after dosing alone and after dosing with JI-101. The pharmacodynamic arm had no separate comparator arm. Because allocation was non-randomized, differences between the two arms would not be interpreted as a like-for-like treatment comparison.
Primary question
The structured primary outcome asks how JI-101 affects the area under the concentration-time curve of everolimus, also called RAD001 in the record. Separately, the study summary describes progression-free survival at 2 moths as the primary objective of the pharmacodynamic part, assessed separately in each of the three cohorts. These are distinct questions: one concerns drug exposure, while the other concerns disease progression over time. The registry record does not report results for either question.
3. Trial Design
This study combined a pharmacokinetic drug-interaction assessment with a pharmacodynamic study. The registry lists phase 1 and phase 2, non-randomized allocation, no masking, and a parallel model. Enrollment was 19. The study began in 2010-09, had a primary completion date of 2012-08, and is listed as terminated. The reason for termination is not reported in the registry record.
In the pharmacokinetic arm, four patients were to receive everolimus and JI-101. The summary describes a single 10 mg oral everolimus dose on Day 1 and Day 8, with JI-101 capsules at 200 mg on Day 8 and Day 15. Measurements were planned before dosing and at specified times after dosing to assess everolimus exposure with and without JI-101. The structured primary outcome focuses on the area under the concentration-time curve, or AUC.
The pharmacodynamic arm received JI-101 alone, orally at 200 mg twice daily in 28 day treatment cycles. The study summary identifies three cohorts: advanced low grade endocrine tumors, ovarian cancers, and K-RAS mutant colon cancers. Its stated pharmacodynamic objective was progression-free survival at 2 moths, evaluated separately within each cohort. Tumor response using RECIST criteria and ephrinB4 expression in blood samples were also described, alongside safety and tolerability objectives.
The record describes different purposes and treatment arrangements across the two arms, rather than a randomized comparison between JI-101 and a control. It does not report a protocol rationale for the enrollment, a sample-size justification, or a detailed statistical analysis plan.
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 | Pharmacokinetic Arm Phase 1 | Pharmacodynamic Arm Phase 2 |
|---|---|---|
| STARTED | 4 | 15 |
| COMPLETED | 4 | 10 |
| NOT COMPLETED | 0 | 5 |
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 | Pharmacokinetic Arm - Phase 1 | Pharmacokinetic Arm-Phase II | Total |
|---|---|---|---|---|
| Participants analysed | 4 | 15 | 19 | |
| Age, Continuous | years | 72 (65 to 80) | 60 (35 to 79) | 60 (35 to 80) |
| Sex: Female, Male: Female | Participants | 0 | 12 | 12 |
| Sex: Female, Male: Male | Participants | 4 | 3 | 7 |
6. Primary Endpoint
The registry lists the primary outcome as Effect of JI 101 on Pharmacokinetics Area Under Curve (AUC) (0-inf) of RAD001, measured over pre-dose and at 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after dosing (Cycle 1 Day 1 for RAD001 alone and Cycle 1 Day 8 for RAD001 + JI-101.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | percentage change |
| Endpoint classification | not reduced to a single comparison |
The structured primary outcome measures the effect of JI-101 on the AUC from zero to infinity of RAD001, the name used in the record for everolimus. AUC represents drug exposure over time, rather than a single concentration at one measurement time. Comparing exposure after everolimus alone with exposure after everolimus plus JI-101 is intended to assess whether co-administration is associated with a change in everolimus pharmacokinetics.
The endpoint is described as a mean percentage change, with full range as the dispersion measure. Blood sampling was planned before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after dosing on Cycle 1 Day 1 for RAD001 alone and Cycle 1 Day 8 for RAD001 plus JI-101. The record's description also refers to determining peak concentration through AUC, although AUC and a peak concentration are different pharmacokinetic summaries. The registry does not clarify that wording.
Drug-exposure outcomes are useful in a drug-interaction study because they characterize how exposure changes when drugs are administered together. However, the registry record contains no reported AUC estimate, percentage change, range, or uncertainty measure. It therefore permits a description of the intended measurement, but not a conclusion about the size or precision of any observed pharmacokinetic change.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the intended study questions, but it does not provide outcome estimates. Its structured primary outcome is the mean percentage change in RAD001 AUC from zero to infinity with JI-101, and its summary also describes progression-free survival at 2 moths in each pharmacodynamic cohort. No numerical results for either objective are reported in the registry record. The record lists 0 analyses, so there is no posted statistical analysis to interpret for these outcomes.
This distinction matters because an endpoint description is not itself a result. The planned sampling times and the stated measurement method explain what investigators intended to assess; they do not establish what exposure was observed. Likewise, a stated progression-free survival objective does not indicate how many participants experienced progression, how long they were followed, or what the survival estimate was. Those results are not reported in the registry record.
The two study parts also address different questions. The pharmacokinetic arm examines everolimus exposure with and without JI-101 in four patients. The pharmacodynamic arm gives JI-101 alone and describes disease-related outcomes in three disease cohorts. These arms are not randomized treatment groups, and the record explicitly characterizes allocation as non-randomized. They therefore should not be read as a controlled comparison of JI-101 against everolimus, or of JI-101 against no treatment.
Enrollment was 19 overall, but the record does not give outcome-specific denominators, cohort-specific enrollment, or the number of participants with evaluable measurements. The pharmacokinetic arm is described as including four patients, while the adverse-event record identifies 4 at risk in that arm and 15 in the pharmacodynamic arm. Those safety denominators do not substitute for endpoint-specific analysis populations.
In general, estimates are more informative when accompanied by uncertainty intervals and a clear account of who contributed data. Neither an estimate nor a confidence interval for the primary outcomes is reported in the registry record. The record also does not report whether the planned assessments were completed, how missing observations were handled, or whether all intended analyses were carried out. Consequently, the posted information supports interpretation of the study's structure and aims, but not of the magnitude or precision of its clinical or pharmacokinetic findings.
The status is listed as terminated, and the primary completion date is 2012-08. The reason for termination and any effect of termination on follow-up or outcome availability are not reported in the registry record. Termination alone does not explain why results are absent, nor does it establish what the results would have shown.
9. Statistical Methods Explained
The registry describes a study with two parts and more than one outcome purpose. The structured primary outcome concerns RAD001 AUC, while the study summary assigns a progression-free survival objective to the pharmacodynamic part. The methods and interpretation therefore need to keep the pharmacokinetic and pharmacodynamic questions separate. The record does not report a statistical analysis plan explaining how the two objectives were prioritized or analyzed.
What does AUC measure?
In general, area under the concentration-time curve summarizes drug concentration across a period of time. It is a measure of overall exposure, while a peak concentration describes the highest measured or estimated concentration. The registry specifies AUC from zero to infinity and calls the outcome a mean percentage change. It also describes sampling at pre-dose and at 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after dosing. The record does not provide the individual concentrations, the AUC estimates, the method used to extend the curve beyond observed sampling, or the resulting percentage change.
The comparison in this arm is within the pharmacokinetic question: everolimus is assessed alone and with JI-101. The record describes everolimus dosing on Day 1 and Day 8, and JI-101 dosing on Day 8 and Day 15. Four patients are identified for the pharmacokinetic arm. The registry does not state whether each participant contributed complete paired measurements or how incomplete measurements were treated. Without those details and the observed estimates, the planned within-person exposure assessment cannot be quantitatively interpreted.
How should progression-free survival be understood?
In general, progression-free survival is a time-to-event outcome. It concerns the time until disease progression or another event defined by the study, with participants who have not experienced the event handled according to the analysis method. The registry summary identifies progression-free survival at 2 moths as an objective in each of three cohorts. It does not report the event definition in detail, the date or method used to assess progression, the number of events, censoring rules, or a cohort-specific estimate. No survival analysis method is reported in the registry record.
Assessing cohorts separately means the question is not a single pooled estimate across all tumor types. In general, separate cohort results can differ in precision because the number of participants and events in each cohort may differ. Here, cohort-specific enrollment and outcome denominators are not reported, so precision cannot be evaluated. The registry also does not state whether the cohort-specific assessments were planned as formal hypothesis tests or descriptive summaries.
Why do non-randomized arms matter?
Random allocation is a method for balancing measured and unmeasured participant characteristics across treatment groups on average. This study is listed as non-randomized, and its arms have distinct roles: one evaluates a drug interaction and the other evaluates pharmacodynamic outcomes with JI-101. They are not like-for-like control groups. General comparisons between them would be difficult to interpret because both the assigned regimen and the purpose of the arm differ. The record does not describe adjustment methods that would support a comparative causal analysis.
The masking entry is none. In general, lack of masking can matter when outcomes depend on assessment or reporting, although its relevance varies by endpoint. The registry mentions RECIST tumor response and safety outcomes but does not report who assessed them, whether assessments were independently reviewed, or any procedures intended to limit assessment bias. No specific conclusion about the impact of masking can be drawn from the available record.
What do mean and full range convey?
The primary outcome is specified as a mean with full range. In general, a mean describes the arithmetic center of observed values, while a range describes the minimum and maximum. A range gives some information about spread but does not, by itself, quantify the precision of the mean. A confidence interval is a statistical interval intended to convey uncertainty around an estimate under an analysis model. No confidence interval or other uncertainty interval is reported for the primary endpoint.
In general, pharmacokinetic measures may vary substantially among participants, and a small arm can make estimates sensitive to individual observations. This is a methodological consideration, not a claim about the variability observed in this study: the registry reports no AUC values or range. The study's enrollment and arm descriptions do not establish how precise any estimated drug interaction would be.
What is not available about the analysis?
The registry does not report the statistical model, test, confidence level, covariate adjustment, missing-data method, or analysis population for the primary outcomes. It also does not report a sample-size justification. A planning illustration based on an observed effect is not evidence of the trial's original design rationale, and the registry record does not report observed effects from which to interpret such a calculation. Any planning figures should be treated as illustrations, not as observed power or as a description of the trial's actual design.
In general, over-dispersion occurs when observed variability is greater than a statistical model assumes; if ignored, uncertainty can be understated. The registry does not identify a count model or report count outcomes requiring an over-dispersion assessment, so this concept cannot be connected to a reported analysis in this study. More broadly, method choices need to be judged against the actual endpoint definitions and data, which are not reported for the primary outcomes.
10. Multiplicity, Missing Data and Analysis Populations
The study summary names several outcomes and objectives: everolimus AUC in the drug-interaction part; progression-free survival separately in three pharmacodynamic cohorts; tumor response using RECIST criteria; ephrinB4 expression in blood samples; and safety and tolerability. Considering multiple endpoints or cohorts can create multiplicity: in general, testing several hypotheses increases the chance that at least one result appears statistically noteworthy by chance if no adjustment or prespecified hierarchy is used.
The registry record does not report whether these outcomes were treated as confirmatory or exploratory, whether a hierarchy was specified, or whether any multiplicity adjustment was planned or used. It also does not report p-values or estimates for these outcomes. As a result, the effect of multiplicity on any claimed statistical evidence cannot be assessed. The stated objectives should not be interpreted as proof that each outcome was formally tested.
Missing-data handling is not reported in the registry record. The record does not describe participant flow, the number completing treatment or follow-up, reasons for missing measurements, or methods for handling missing outcome values. It also does not specify analysis populations such as an intention-to-treat or evaluable population. The total enrollment of 19 does not establish how many participants contributed to each endpoint.
For time-to-event outcomes, general methods account for participants whose event time is not observed during follow-up, but the registry does not state the censoring rules or the analysis population for progression-free survival. For the pharmacokinetic endpoint, the record does not say how incomplete sampling or unavailable concentration measurements were handled. These omissions limit interpretation of both the potential bias and the precision of the intended analyses.
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 |
|---|---|---|---|
| Pharmacokinetic Arm | 1 | 4 | 25.0% |
| Pharmacodynamic Arm | 4 | 15 | 26.7% |
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 |
|---|---|
| Pharmacokinetic Arm | 4 of 4 |
| Pharmacodynamic Arm | 12 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Pharmacokinetic Arm | Pharmacodynamic Arm |
|---|---|---|---|
| Small bowel obstruction | Gastrointestinal disorders | 0 of 4 | 3 of 15 |
| Hypertension | Vascular disorders | 1 of 4 | 1 of 15 |
| Constipation | Gastrointestinal disorders | 0 of 4 | 1 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pharmacokinetic Arm | Pharmacodynamic Arm |
|---|---|---|---|
| Hypertension | Vascular disorders | 3 of 4 | 10 of 15 |
| abdominal pain | Gastrointestinal disorders | 1 of 4 | 5 of 15 |
| fatigue | Investigations | 2 of 4 | 4 of 15 |
| nausea | Gastrointestinal disorders | 1 of 4 | 5 of 15 |
| diarrhea | Gastrointestinal disorders | 1 of 4 | 4 of 15 |
| Anorexia | Gastrointestinal disorders | 1 of 4 | 3 of 15 |
| lymphopenia | Blood and lymphatic system disorders | 1 of 4 | 3 of 15 |
| vomiting | Gastrointestinal disorders | 1 of 4 | 2 of 15 |
| Elevated ALT | Metabolism and nutrition disorders | 0 of 4 | 2 of 15 |
| Elevated AST | Metabolism and nutrition disorders | 0 of 4 | 2 of 15 |
Serious events with the highest arm-level rate: hypertension (25.0%), small bowel obstruction (20.0%), constipation (6.7%).
The adverse-event record separates serious events from other adverse events and reports the number at risk and the number affected in each arm. In the pharmacokinetic arm, 4 participants were at risk for serious adverse events and 1 was affected; 4 were at risk for other adverse events and 4 were affected. In the pharmacodynamic arm, 15 were at risk for serious adverse events and 4 were affected; 15 were at risk for other adverse events and 12 were affected.
These counts describe the registry's safety entries, not a randomized comparison. The arms differ in purpose and treatment regimen, and the study was non-randomized. The counts therefore should not be used to attribute differences to a treatment effect. The registry lists hypertension at 25.0%, small bowel obstruction at 20.0%, and constipation at 6.7% among its top serious terms. It does not provide enough context in these entries to interpret those percentages as comparative risks between arms.
Deaths are listed as null, so death information is not reported in the registry record. The entries also do not establish event timing, duration, severity grading beyond the serious-event classification, or causal attribution. The adverse-event figures should be read as recorded counts within the stated at-risk groups, not as a complete account of safety or proof of causation.
12. What the Result Does, and Does Not, Mean
The record establishes that the study was designed to address a drug-interaction question and a separate pharmacodynamic question. For the former, it planned to measure everolimus AUC with and without JI-101. For the latter, it described progression-free survival at 2 moths in each of three tumor cohorts, as well as tumor response and ephrinB4 expression. It also listed safety and tolerability objectives.
What the registry does not establish is the magnitude of any observed change in AUC, progression-free survival, tumor response, or ephrinB4 expression. No numerical results for those endpoints are reported in the registry record. There are no posted estimates or confidence intervals with which to judge precision, and the listed outcome descriptions cannot be treated as findings.
The safety entries provide counts of participants affected within each arm, but they do not support a causal comparison. The study was non-randomized, and the two arms served different purposes. Event counts alone do not establish that JI-101 caused an event, nor do they show how risk would compare with a control group. Death data are not reported in the registry record.
In general, a clinical study's results are most useful when the endpoint definitions, analysis populations, missing-data handling, and uncertainty estimates are available alongside the numerical estimates. Those details are not reported for the primary outcomes. The registry record therefore supports a careful account of what investigators intended to study and the design features that constrain comparisons, but it does not support conclusions about the size, direction, or precision of treatment-related effects.
The study is listed as terminated. The registry does not report the reason for termination or explain whether this affected the completion of planned assessments. Termination does not, on its own, indicate whether an intervention was beneficial, harmful, or ineffective.
13. Why This Trial Matters Statistically
This study is statistically notable because it combines a pharmacokinetic interaction assessment with a pharmacodynamic investigation in distinct cancer cohorts. These questions require different outcome definitions and analytic approaches. Drug exposure measured through AUC is not interchangeable with progression-free survival, tumor response, or safety. Treating them as one overall comparison would obscure what each part was intended to assess.
The record also illustrates why a stated primary objective and a reported result must be distinguished. The structured primary outcome concerns the effect of JI-101 on RAD001 AUC, while the summary describes progression-free survival at 2 moths as the pharmacodynamic objective, evaluated separately by cohort. The registry does not report numerical results for either. Recognizing the separate objectives prevents an endpoint description from being mistaken for evidence about an outcome.
Non-randomized allocation is another important feature. The pharmacokinetic and pharmacodynamic arms differ in purpose, participants, and regimen, so they are not control and treatment groups in a randomized comparison. This constrains what can be inferred from differences between their recorded counts or outcomes.
Finally, the record identifies enrollment of 19 and a terminated status but does not report outcome-specific denominators, analysis methods, missing-data handling, or uncertainty estimates. These omissions are consequential for judging the reliability and precision of any result. The record is therefore useful for understanding the study's design and intended measurements, while also demonstrating how limited interpretation becomes when endpoint results and analytic details are unavailable.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record leaves several trial-specific limitations unresolved. Although total enrollment is 19, it does not report enrollment by tumor cohort, the number who completed treatment, or endpoint-specific analysis populations. The pharmacokinetic arm is described as including four patients, but the record does not say how many had complete measurements at all planned sampling times. This prevents assessment of the amount of information available for the AUC outcome.
The listed structured primary outcome and the summary's pharmacodynamic objective address different questions. The registry does not explain the relationship or priority between the AUC endpoint and progression-free survival at 2 moths. Nor does it report the operational definition of progression-free survival, the event assessment schedule, censoring rules, or cohort-specific estimates. The reason for termination and its effect on outcome collection are not reported in the registry record.
The pharmacodynamic arm includes three different cancer cohorts, but cohort sizes and separate results are not reported. Pooling these conditions could obscure differences, while separate analyses could be imprecise if group sizes were small; the actual group sizes and precision cannot be assessed from the registry record. No adjustment strategy or comparative analysis is reported.
The record does not report details about who assessed tumor response, how ephrinB4 expression was analyzed, or how missing values were handled. It also does not provide a statistical analysis plan or sample-size justification. Finally, adverse-event counts lack information on timing and attribution, and death data are not reported. These limitations concern the information available in the registry record; they do not establish what occurred during the study.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of JI-101 in Patients With Advanced Low Grade Endocrine Tumors, Ovarian Cancers or K-RAS Mutant Colon Cancers — NCT01149434.
- Registry record last updated 2014-10-06; status last verified 2014-09.
- Results first posted 2014-09-25.
- 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
NCT01149434 is a phase 1 and phase 2, non-randomized, unmasked study listed as parallel, with enrollment of 19. It studied JI-101 in a pharmacokinetic arm with everolimus and a pharmacodynamic arm in patients with advanced low grade endocrine tumors, ovarian cancers, or K-RAS mutant colon cancers. The pharmacokinetic question concerned the effect of JI-101 on RAD001 AUC; the summary also identified progression-free survival at 2 moths as the pharmacodynamic objective for each cohort.
The record lists the study as terminated, with a start date of 2010-09 and primary completion date of 2012-08. It reports no analyses and no numerical results for the primary outcomes. The reason for termination, outcome-specific analysis populations, missing-data methods, and statistical analysis plan are not reported in the registry record. Safety entries include affected-participant counts by arm, while death information is not reported.