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 LDE225 for Patients With PTCH1 or SMO Mutated Tumors (NCT02002689), a na phase 2 study. The primary outcome is Summary of Overall Response (ORR) and Clinical Benefit (CBR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02002689 |
| Phase | Phase 2 |
| Condition | PTCH1 or SMO Activated Solid and Hematologic Tumors |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Patients with PTCH1- or SMO-activated solid or hematologic tumors. The primary outcome population is identified as the full analysis set.
Intervention
LDE225, an oral drug, at 800 mg once daily on a continuous dosing schedule.
Comparator
There was no comparator arm. The registry record identifies a single-group study and no allocation.
Primary question
Whether investigator-assessed overall response and clinical benefit with LDE225 merited further study in tumors with the specified pathway mutations. Clinical benefit included complete response, partial response, or stable disease lasting at least 16 weeks.
The study was described as signal seeking: its purpose was to assess whether treatment showed sufficient efficacy to warrant further study. This is a screening question, not a randomized comparison of LDE225 against another treatment or against no treatment. The registry record names both solid tumors and hematologic malignancies, and describes response assessment by tumor type. For solid tumors, the stated response criteria were RECIST 1.1. The primary endpoint description does not give a single pooled response estimate or report how results were distributed across tumor types.
The record does not report the primary response or clinical-benefit results. It therefore does not establish how many participants met either outcome, nor how those outcomes varied by tumor type. The question can be described from the planned endpoint, but the posted results do not answer it numerically.
3. Trial Design
This was a phase II, single-group study of LDE225. The registry lists enrollment of 10 and identifies no allocation or masking. With no control group, the design can describe outcomes among participants receiving LDE225 but cannot directly compare those outcomes with a concurrent alternative. The registry record does not report a randomized treatment assignment, masking procedures, or a comparator regimen.
The listed treatment was LDE225 800 mg in hard gelatin capsules, taken orally once daily on a continuous dosing schedule. The primary outcome timeframe was 16 weeks. The registry lists progression-free survival as a secondary outcome, including timing and estimated rate, and describes Kaplan-Meier estimates in months. Numerical results for those outcomes are not reported in the registry record.
The study began in 2014-02, had a primary completion date of 2015-03, and is listed as terminated. The reason for termination is not reported in the registry record. The record does not state how many participants completed treatment or follow-up, or whether all enrolled participants contributed to every outcome.
The registry lists three outcome measures and zero analyses. Although the primary endpoint description identifies the full analysis set, the record does not provide the analysis methods or a participant flow by analysis population. Sample-size justification, planned interim analyses, and a detailed statistical plan are not reported in the registry record. The single-group design and limited enrollment are important when considering how much information the study could provide, but the absent outcome estimates prevent assessment of the observed response signal.
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 | Sonidegib |
|---|---|
| STARTED | 10 |
| COMPLETED | 0 |
| NOT COMPLETED | 10 |
Reasons for not completing this period:
| Reason | Sonidegib |
|---|---|
| Disease Progression | 7 |
| Adverse Event | 3 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set
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 | Sonidegib |
|---|---|---|
| Participants analysed | 10 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 |
| Age, Categorical: >=65 years | Participants | 6 |
| Age, Continuous | years | 63.2 (SD 7.64) |
| Sex: Female, Male: Female | Participants | 6 |
| Sex: Female, Male: Male | Participants | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Summary of Overall Response (ORR) and Clinical Benefit (CBR), measured over 16 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percent responders |
| Endpoint classification | Binary Endpoint |
The primary outcome is described as a summary of overall response rate and clinical benefit rate, assessed by the investigator. Clinical benefit rate includes participants with complete response, partial response, or stable disease lasting at least 16 weeks. Overall response rate concerns complete or partial responses; for solid tumors, the stated assessment criteria were RECIST 1.1. The registry also describes categories including stable disease, progressive disease, and not evaluable for solid tumors, with response categories to be reported for each applicable hematologic tumor type.
These measures answer related but distinct questions. Overall response focuses on tumor shrinkage meeting response criteria. Clinical benefit also counts stable disease when it persists for the specified duration. Both can be useful in a signal-seeking study because they describe observed tumor status under treatment, while the clinical-benefit definition includes sustained disease stability as well as response.
The registry description says counts, percentages, and 95% exact confidence intervals were to be reported for response rates. However, the actual counts, percentages, and confidence intervals are not reported in the registry record. The endpoint description therefore explains what was intended to be measured, not what participants experienced. The registry does not report a primary-outcome estimate that can be interpreted for magnitude or precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes that this was a small, single-group phase II study, with enrollment of 10, and that its stated purpose was to seek a treatment signal. It also describes the investigator-assessed response and clinical-benefit outcomes. It does not report the numerical results for those primary outcomes. Without the number of participants meeting the endpoint, an estimated response rate, or its confidence interval, the strength and precision of any observed response signal cannot be assessed from the posted results.
This is a distinction between a missing result and a result showing no responses. The record does not report a response estimate; that is not evidence that the response rate was zero. It is likewise not evidence that a response occurred. The endpoint counts and estimates are simply not reported in the registry record.
The lack of a comparator also limits interpretation. Any outcomes observed in a single group would describe participants treated in this study, but would not by themselves establish how outcomes compare with another treatment or what would have happened without LDE225. Differences in tumor type and response assessment may also matter: the record describes solid and hematologic tumors and sets out assessment approaches by type, but does not report the outcome results by type.
Confidence intervals were specified in the endpoint description, but their values are absent. An interval would communicate the uncertainty around an estimated response rate; without it, the precision of the primary estimate cannot be judged. The modest enrollment listed in the record also makes it important to avoid treating a potential signal as a definitive estimate. No sample-size justification is reported, and there is no basis in the record for concluding that the study was sized to detect a particular effect.
The registry lists progression-free survival outcomes as secondary measures, but numerical PFS estimates are not reported in the registry record. The record also lists zero analyses. Accordingly, the evidence available from the posted results supports description of the design and intended outcomes, but not a quantitative conclusion about efficacy, comparative benefit, or the consistency of outcomes across tumor types.
9. Statistical Methods Explained
The endpoint description calls for percentages and 95% exact confidence intervals for response rates. A response rate is a proportion: it relates the number of participants meeting a defined response criterion to the relevant analysis population. The registry record does not report the numerator, the resulting percentage, or the interval for the primary endpoint, so those quantities cannot be interpreted from the posted results.
What a confidence interval communicates
In general, a confidence interval expresses uncertainty around an estimate using a method with a stated long-run coverage property. It is not a guarantee that the true value lies within a particular calculated interval, and it is not a probability statement about the parameter after observing the data. A wider interval indicates less precision than a narrower interval. For a response proportion based on a limited number of participants, exact methods are often used because they are designed for binomial counts and do not rely on the same large-sample approximation used by some other approaches. The record specifies a 95% exact interval but does not report its result.
Exact intervals do not remove uncertainty caused by limited enrollment, nor do they address whether participants represent other patient groups. They quantify sampling uncertainty under the method's assumptions. They also do not correct for an uncontrolled design, differences among tumor types, missing outcome data, or choices made in defining and assessing response.
How to read the response definitions
Overall response and clinical benefit use different endpoint rules. For solid tumors, the stated RECIST 1.1 categories include complete and partial response for overall response; clinical benefit additionally includes stable disease lasting at least 16 weeks. The endpoint description says the investigator assessed response. Investigator assessment is the stated basis for the outcome; the registry does not report whether independent review was used or how disagreements were handled. The record describes reporting by solid tumor and applicable hematologic tumor type, but does not report the resulting category counts.
These definitions make classification dependent on both tumor assessment and timing. A participant's status must meet the relevant response category, and the clinical-benefit definition also requires the specified duration of stable disease. General statistical interpretation should therefore consider how response was assessed, how evaluability was determined, and whether follow-up was sufficient. Those operational details are not reported in the registry record.
Single-group estimation and comparison
A single-group study can estimate outcomes within the treated group if the relevant results and analysis population are reported. It cannot produce a randomized between-group treatment contrast when there is no comparator arm. A within-group response estimate is not equivalent to an estimate of the causal effect of treatment: it does not separate treatment effects from the natural course of disease, participant selection, or other influences. This is a general limitation of uncontrolled designs, not a claim about what occurred in this study.
The record lists enrollment of 10 and identifies the full analysis set for the primary outcome. It does not specify the full analysis set rules, the handling of participants without an assessment, or the handling of unevaluable outcomes. Those details matter because the denominator determines the response proportion and because different rules can lead to different estimates.
Planning calculations and power
The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. Such calculations are hypothetical planning exercises, not observed power. They do not describe a design actually used in this single-group study, which has no comparator allocation. The registry record does not report the numerical illustration results or a trial-specific sample-size justification. No planned sample-size target or calculation should therefore be inferred from those illustrations.
For time-to-event outcomes, general methods such as Kaplan-Meier estimation describe the estimated probability of remaining event-free over time while accounting for differing follow-up. The registry lists Kaplan-Meier estimates for progression-free survival, but does not report the estimates, event counts, censoring details, or analysis procedures. These omissions prevent statistical interpretation of the PFS results.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three outcome measures and zero analyses. It identifies overall response and clinical benefit as the primary outcome topic and progression-free survival as a secondary outcome. The endpoint description also encompasses response categories and, where applicable, distinct tumor types. Assessing several outcomes or subgroups can create multiplicity: when many statistical questions are considered, the chance of at least one apparently notable finding can increase. Whether and how that concern was addressed is not reported in the registry record. No multiplicity adjustment or hierarchy among outcomes is described.
The record identifies the full analysis set for the primary outcome, but does not define membership in that set. It does not state how missing assessments, participants who discontinued treatment, unevaluable responses, or incomplete follow-up were handled. These choices can affect both the numerator and denominator of a response estimate. The endpoint description includes a not-evaluable category for solid tumors, but the registry does not report how many participants were classified that way or how such cases were treated in any rate calculation.
The registry does not report whether an analysis plan specified in advance how these issues would be handled. Nor does it give a missing-data sensitivity analysis or a breakdown of participants included in each outcome analysis. Consequently, it is not possible to determine whether the posted analysis population and missing-data handling were consistent across outcomes or tumor categories. These are reporting gaps; they do not establish that data were missing or that any particular analysis choice was made.
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 |
|---|---|---|---|
| LDE225 | 7 | 10 | 70.0% |
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 |
|---|---|
| LDE225 | 10 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | LDE225 |
|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 2 of 10 |
| Dehydration | Metabolism and nutrition disorders | 2 of 10 |
| Dysphagia | Gastrointestinal disorders | 1 of 10 |
| Small intestinal obstruction | Gastrointestinal disorders | 1 of 10 |
| Pneumonia | Infections and infestations | 1 of 10 |
| Failure to thrive | Metabolism and nutrition disorders | 1 of 10 |
| Muscular weakness | Musculoskeletal and connective tissue disorders | 1 of 10 |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 1 of 10 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 10 |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | 1 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | LDE225 |
|---|---|---|
| Nausea | Gastrointestinal disorders | 8 of 10 |
| Fatigue | General disorders | 6 of 10 |
| Decreased appetite | Metabolism and nutrition disorders | 5 of 10 |
| Vomiting | Gastrointestinal disorders | 4 of 10 |
| Weight decreased | Investigations | 4 of 10 |
| Constipation | Gastrointestinal disorders | 3 of 10 |
| Diarrhoea | Gastrointestinal disorders | 3 of 10 |
| Urinary tract infection | Infections and infestations | 3 of 10 |
| Alanine aminotransferase increased | Investigations | 3 of 10 |
| Aspartate aminotransferase increased | Investigations | 3 of 10 |
Serious events with the highest arm-level rate: abdominal pain (20.0%), dehydration (20.0%), dysphagia (10.0%), small intestinal obstruction (10.0%), pneumonia (10.0%).
For the LDE225 group, the registry reports 10 participants at risk for serious adverse events and 7 affected. For other adverse events, it reports 10 at risk and 10 affected. Deaths are not reported in the registry record. These counts describe the safety summaries as recorded; they do not by themselves indicate whether an event was caused by treatment.
The listed serious adverse event terms and percentages are abdominal pain, 20.0%; dehydration, 20.0%; dysphagia, 10.0%; small intestinal obstruction, 10.0%; pneumonia, 10.0%; and failure to thrive, 10.0%. They should be read as reported event terms, not as mutually exclusive groups. The registry does not say whether participants could have experienced more than one listed event, and the percentages should not be added together to estimate the proportion with any serious event.
The record does not report event timing, duration, severity grades, treatment relatedness, exposure-adjusted rates, or the criteria used to classify events. Nor does it provide a detailed account of safety follow-up. The counts therefore describe the posted safety summary, but provide limited information about individual events or their relationship to LDE225. The absence of reported deaths should not be interpreted as evidence that no deaths occurred; the death value is not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The study record describes a phase II, signal-seeking investigation of LDE225 in patients with PTCH1- or SMO-activated tumors. It specifies a planned primary outcome based on investigator-assessed overall response and clinical benefit, with a clinical-benefit definition that includes sustained stable disease. It also reports safety counts and lists secondary progression-free survival outcomes.
What the record does not establish is the observed primary response rate or clinical-benefit rate. The outcome counts, percentages, and confidence intervals are not reported in the registry record. As a result, the study's primary efficacy question cannot be answered quantitatively from the posted results. Missing results must not be read as either a positive or a negative finding.
Even if within-group outcome estimates were available, the absence of a comparator would mean that they describe outcomes in this treated group rather than a randomized treatment effect. The registry also covers solid and hematologic tumors, but does not provide outcome estimates by tumor type. It is therefore not possible to determine from the record whether outcomes were similar across types or concentrated in a particular group.
The reported adverse-event counts identify participants affected in the registry's safety summaries, while the listed percentages identify specific serious adverse event terms. They do not establish causality, comparative safety, or the frequency of unlisted events. The record lacks important contextual details, including event timing and attribution.
Overall, the registry record documents the study question, treatment schedule, design, selected safety summaries, and planned outcomes. It does not provide the primary results or enough statistical detail to assess efficacy precision, subgroup consistency, or comparative effects. Any conclusion should remain within those limits.
13. Why This Trial Matters Statistically
This study illustrates why the design and completeness of outcome reporting matter as much as the endpoint definition. The registry describes a signal-seeking phase II study with enrollment of 10 and no comparator. Such a design can be used to characterize outcomes in a treated group, but it does not offer a randomized comparison that separates treatment effects from other explanations for observed outcomes.
The endpoint definitions are also consequential. Overall response counts complete and partial responses under the stated assessment approach, while clinical benefit includes stable disease maintained for at least 16 weeks. Reporting the criteria, analysis population, counts, and uncertainty together is necessary for readers to understand what a response estimate represents. Here, the registry describes the intended measures but does not report their numerical results or confidence intervals.
The record spans solid and hematologic tumors and describes reporting by tumor type. That makes transparent subgroup and category reporting important: an overall figure could conceal variation across clinically different groups. Since the registry does not report those outcome results, the consistency of any signal cannot be evaluated.
Finally, the registry's safety counts can be read only alongside their limitations. Participant counts and event terms are useful descriptive information, but event attribution, timing, and overlap are not reported. This study therefore provides a clear example of how a registry can document a design and outcome framework while leaving readers unable to assess the central efficacy estimate. Statistical interpretation depends on the results and analysis details being available, not only on the planned endpoint.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation for statistical interpretation is that the registry does not report the primary outcome counts, rates, or confidence intervals. The stated response and clinical-benefit definitions cannot substitute for observed results. Progression-free survival is listed as a secondary outcome, but its numerical estimates and event information are also not reported in the registry record.
The study has a single-group design and no comparator, so it cannot support a randomized between-group treatment contrast. Enrollment is listed as 10, but the record does not describe participant flow, treatment completion, follow-up completeness, or the number analyzed for each outcome. Although the full analysis set is named for the primary outcome, its membership rules are not reported.
Population breadth is another interpretive constraint: the registry includes solid and hematologic tumors and indicates that response categories were to be reported by tumor type. The results by type are not reported, so heterogeneity or consistency cannot be assessed. The registry also does not report details of response review, missing-data handling, multiplicity control, a sample-size justification, or interim analyses. These are not evidence that any specific procedure was or was not used; the details are not reported in the registry record.
The study is listed as terminated, but the reason is not reported. Safety summaries give affected-participant counts and selected serious adverse event terms, without reported attribution, timing, or overlap. These gaps limit interpretation of both efficacy and safety and should not be resolved by assuming unreported methods or outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: LDE225 for Patients With PTCH1 or SMO Mutated Tumors — NCT02002689.
- Registry record last updated 2016-05-02; status last verified 2016-04.
- Results first posted 2016-05-02.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT02002689 is a phase II, single-group study of LDE225 for patients with PTCH1- or SMO-activated solid and hematologic tumors. The registry lists enrollment of 10, oral LDE225 at 800 mg once daily, and a primary outcome covering investigator-assessed overall response and clinical benefit at 16 weeks. The study began in 2014-02, had a primary completion date of 2015-03, and is listed as terminated.
The registry describes the primary outcome definitions and reports safety counts, including 7 participants affected by serious adverse events among 10 at risk. It lists three outcome measures and zero analyses. Primary response results, progression-free survival estimates, the reason for termination, and several analysis details are not reported in the registry record.