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 Dose Escalating Study of the Safety and Efficacy of Patupilone, q3w, in Patients With Non-small Cell Lung Cancer (NCT00171834), a non-randomized phase 1, phase 2 study. The primary outcome is Phase I: Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00171834 |
| Phase | Phase 1, Phase 2 |
| Condition | Carcinoma, Non-Small-Cell Lung |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 89 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with non-small cell lung cancer who had progressed after prior chemotherapy. For the Phase I primary endpoint, the MTD-determining population included patients who completed Cycle 1 according to protocol or discontinued because of a DLT. The registry record does not report further eligibility details for this endpoint population.
Intervention
The intervention was patupilone, administered every three weeks. In Phase I, dose escalation began at 6.5 mg/m^2 and proceeded through the dose steps described in the registry record, up to 13.0 mg/m^2. Phase II included a 10 mg/m^2 NSCLC cohort and a 10 mg/m^2 cohort for NSCLC with brain metastases.
Comparator
There was no randomized control group. The study was non-randomized and used a single-group model. Dose groups represent successive dose levels or study cohorts, not like-for-like randomized treatment arms; differences between them cannot be interpreted as randomized comparisons.
Primary question
The Phase I primary question was how many DLTs occurred during Cycle 1 at the explored patupilone doses, and whether any dose met the protocol definition for the MTD. The registry says no more than one DLT occurred at any explored dose level up to 13 mg/m^2, so the protocol-defined MTD was not reached. This endpoint addresses dose-limiting toxicity during dose escalation, not comparative efficacy.
3. Trial Design
This was a completed, open-label, non-randomized Phase I/II study sponsored by Novartis Pharmaceuticals. It enrolled 89 participants and investigated patupilone in non-small cell lung cancer. The study started in 2003-08, and primary completion was recorded as 2008-09. The registry describes a single-group model and no masking. There was no randomized comparator, so the dose cohorts should not be treated as controlled treatment arms.
The study objective was to evaluate the maximum tolerated dose, safety, and efficacy of patupilone in patients whose NSCLC had progressed after prior chemotherapy. Phase I used dose escalation to evaluate DLTs and determine whether the protocol-defined MTD was reached. The planned escalation began at 6.5 mg/m^2, with steps of 0.5 mg/m^2 until 12 mg/m^2 and then steps of 1 mg/m^2 through 13.0 mg/m^2. DLTs for the primary endpoint were assessed during Cycle 1, defined as 21 days.
The protocol description defines MTD as the highest dose administered every three weeks at which not more than one out of six patients experienced a DLT, using a standard 3+3 design. The record reports that no more than one DLT occurred at any explored dose level up to 13 mg/m^2; consequently, the protocol-defined MTD was not reached in this study.
Phase II included a 10 mg/m^2 NSCLC cohort and a 10 mg/m^2 cohort of patients with NSCLC and brain metastases. The registry lists outcomes concerning response, overall survival, time to progression, stable disease, and response duration. Results for those outcomes are not reported in the registry record. The record lists eight outcome measures and zero analyses. It does not report a statistical analysis plan or a sample-size justification.
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.
Only the first 6 of 7 groups are shown.
Overall Study
| Stage | Patupilone ≤7.0 mg/m^2 (Phase I) | Patupilone 7.5-8.0 mg/m^2 (Phase I) | Patupilone 8.5-9.5 mg/m^2 (Phase I) | Patupilone 10.0-11.5 mg/m^2 (Phase I) | Patupilone 12.0-13.0 mg/m^2 (Phase I) | Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort |
|---|---|---|---|---|---|---|
| STARTED | 6 | 12 | 12 | 12 | 8 | 35 |
| Completed 6 Cycles of Treatment | 0 | 0 | 1 | 0 | 2 | 1 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 12 | 12 | 12 | 8 | 35 |
Reasons for not completing this period:
| Reason | Patupilone ≤7.0 mg/m^2 (Phase I) | Patupilone 7.5-8.0 mg/m^2 (Phase I) | Patupilone 8.5-9.5 mg/m^2 (Phase I) | Patupilone 10.0-11.5 mg/m^2 (Phase I) | Patupilone 12.0-13.0 mg/m^2 (Phase I) | Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort |
|---|---|---|---|---|---|---|
| Adverse Event | 2 | 1 | 3 | 2 | 2 | 15 |
| Withdrawal by Subject | 0 | 2 | 0 | 1 | 1 | 1 |
| Death from study indication | 0 | 1 | 0 | 0 | 1 | 0 |
| Disease Progression | 4 | 8 | 8 | 9 | 2 | 18 |
| Treatment Duration Completed | 0 | 0 | 1 | 0 | 2 | 1 |
Analysis population for the primary outcome, as defined in the registry: Maximum tolerated dose (MTD) determining population.included all patients who completed the first treatment cycle (Cycle 1) according to protocol or discontinued due to a DLT. The first cycle data from this patient population were used to determine the MTD in the Phase I part of the study.
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.
Only the first 6 of 8 groups are shown.
| Characteristic | Unit | Patupilone ≤7.0 mg/m^2 (Phase I) | Patupilone 7.5-8.0 mg/m^2 (Phase I) | Patupilone 8.5-9.5 mg/m^2 (Phase I) | Patupilone 10.0-11.5 mg/m^2 (Phase I) | Patupilone 12.0-13.0 mg/m^2 (Phase I) | Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort |
|---|---|---|---|---|---|---|---|
| Participants analysed | 6 | 12 | 12 | 12 | 8 | 35 | |
| Age, Continuous | years | 58.3 (SD 12.01) | 59.4 (SD 8.98) | 57.8 (SD 9.31) | 57.6 (SD 9.07) | 56.3 (SD 13.31) | 63.3 (SD 8.04) |
| Sex: Female, Male: Female | Participants | 3 | 5 | 4 | 4 | 2 | 10 |
| Sex: Female, Male: Male | Participants | 3 | 7 | 8 | 8 | 6 | 25 |
| Race/Ethnicity, Customized: Caucasian | participants | 6 | 12 | 11 | 12 | 8 | 35 |
| Race/Ethnicity, Customized: Black or African American | participants | 0 | 0 | 1 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Phase I: Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD), measured over Cycle 1 (21 days).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Dose Limiting Toxicity (DLT) |
| Endpoint classification | not reduced to a single comparison |
The primary Phase I endpoint was the number of total dose-limiting toxicities during dose escalation to determine the maximum tolerated dose. DLTs were assessed during Cycle 1, defined as 21 days. The endpoint was restricted to the MTD-determining population: patients who completed the first treatment cycle according to protocol or discontinued because of a DLT. The registry says first-cycle data from this population were used to determine the MTD.
This endpoint is used in dose-escalation research because early treatment-cycle toxicity can identify dose levels at which treatment is not tolerable under the study's protocol definition. The registry describes a standard 3+3 design and defines MTD as the highest dose at which not more than one out of six patients experienced a DLT. That definition is a protocol rule for dose selection; it is not itself a test of efficacy or a comparison against another treatment.
The registry reports that no more than one DLT occurred at any explored dose level up to 13 mg/m^2. It therefore states that the MTD, as defined by the protocol, was not reached. This is a statement about the observed DLT counts and the study's dose-escalation rule. It does not establish that higher doses would be safe, nor does the registry record provide a comparative estimate of treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The main statistical finding is a dose-escalation result, not an efficacy comparison. The registry reports that, during the Cycle 1 assessment, no more than one DLT occurred at any explored dose level up to 13 mg/m^2. Under the protocol's stated definition, this meant that the MTD was not reached. The finding is limited to the doses explored, the DLT definition, and the MTD-determining population specified in the record.
The protocol definition uses a small cohort rule: the highest dose with not more than one DLT among six patients qualifies as the MTD. This type of rule provides a practical decision structure for escalation, but it does not produce a precise estimate of the probability of toxicity at each dose. With limited observations at a dose, the underlying risk can remain uncertain even when few DLTs are observed. The registry record does not provide confidence intervals or a model-based estimate of dose-specific toxicity.
The adverse-event listing provides counts for serious adverse events and other adverse events by dose group or Phase II cohort. These are descriptive safety data. The groups are not randomized comparators, and their sizes and clinical composition differ. It would therefore be inappropriate to interpret the observed differences between groups as evidence that one dose or cohort caused more or fewer events than another. The record does not report an adjusted comparison.
Several secondary outcomes are listed, including response, overall survival, time to progression, stable disease, and response duration. Results for those outcomes are not reported in the registry record. Thus, the available record does not support an interpretation of tumor response or time-to-event outcomes. The stated study objective included efficacy, but an objective is not a result.
The record also does not report confidence intervals, p-values, or analysis methods for the outcomes. Without such information, precision cannot be assessed beyond the reported counts and the protocol's DLT rule. The absence of reported inferential results is not evidence that an outcome was absent; it means that the registry record does not provide an estimate to interpret.
Because allocation was non-randomized and the study used a single-group model, the treatment cohorts do not supply an unbiased control comparison. The dose-level information is useful for understanding the protocol's escalation experience, but it cannot separate dose effects from differences in cohort composition or other factors. The registry findings should be read as descriptive evidence from this study, not as a causal contrast between treatment strategies.
9. Statistical Methods Explained
What does the dose-escalation rule do?
In a dose-escalation study, investigators examine safety at successive dose levels and apply a prespecified rule to decide whether a dose can be advanced or qualifies as the maximum tolerated dose. The registry describes a standard 3+3 design. Under its definition, MTD was the highest dose administered every three weeks at which not more than one out of six patients experienced a DLT. This is a protocol decision rule, not a statistical test comparing patupilone with a control treatment.
The dose sequence began at 6.5 mg/m^2, increased in steps of 0.5 mg/m^2 until 12 mg/m^2, and then used steps of 1 mg/m^2 through 13.0 mg/m^2. The registry states that DLTs were assessed in Cycle 1, which lasted 21 days. It reports no more than one DLT at any explored dose level up to 13 mg/m^2, and says the MTD was not reached under the protocol definition.
What does a DLT count tell the reader?
A count records how many participants in the defined assessment population experienced an event meeting the DLT criteria. Counts are easy to connect to a dose-escalation rule, but they do not by themselves show how precisely the underlying toxicity risk has been estimated. General statistical principle: when the number of observations is limited, an observed count can be compatible with a range of underlying event probabilities. Confidence intervals, if reported, would express uncertainty around an estimated quantity; none are reported for the primary endpoint in the registry record.
The endpoint population also matters. The record says it included patients who completed Cycle 1 according to protocol or discontinued because of a DLT, and that first-cycle data from this population were used for MTD determination. This is not necessarily identical to every participant enrolled in the study. The registry record does not report the number in the MTD-determining population or participant-level disposition for this endpoint.
Why is the cohort structure important?
The trial was non-randomized and used a single-group model. Phase I dose groups reflect a dose-escalation process, and the Phase II cohorts were defined by dose and disease cohort. They are not randomized groups with an equivalent control condition. General statistical principle: randomization helps balance measured and unmeasured prognostic factors, while non-randomized cohort differences can reflect patient selection, timing, dose assignment, or other factors. Therefore, comparisons of event counts across these dose groups should remain descriptive rather than causal.
The registry's adverse-event listings distinguish serious adverse events from other adverse events, and give an at-risk count and an affected count for each group. These counts indicate how many participants were listed as at risk and how many were recorded with an event in that category. They should not be conflated with the primary DLT count: the endpoint definitions and observation periods may differ, and the record does not state that every serious or other adverse event met DLT criteria.
What would an inferential analysis add?
An inferential analysis could report an effect estimate, uncertainty interval, or statistical test for a defined question. For the primary endpoint, a dose-specific toxicity estimate with an uncertainty interval could communicate precision more fully than the escalation rule alone. For a comparative efficacy question, a suitable control group and a prespecified analysis would be needed. The registry lists no analyses, and these inferential results are not reported in the registry record.
General statistical principle: p-values summarize the compatibility of data with a specified null model, conditional on the assumptions and analysis used; they do not measure the size or clinical importance of an effect. Confidence intervals describe a range of values compatible with the data and model, and are often more informative about precision. Neither can be reconstructed from the information reported for the primary endpoint without making unsupported assumptions.
How should planning calculations be distinguished from trial results?
Sample-size calculations are planning illustrations, not observations from the completed trial. The registry record does not report a sample-size justification for this study. It also does not report an observed effect estimate for the listed secondary outcomes from which an effect-based planning calculation could be interpreted. Any planning illustration based on an observed effect would depend on its assumptions and would not represent observed power or a result from the trial.
The record's stated planning assumptions refer to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a fraction of an observed effect. Those are planning assumptions, not the design of this single-group non-randomized study. No planning outputs are reported in the registry record. They therefore should not be read as trial findings or as evidence of the study's power.
What is not available for independent statistical review?
The registry record does not report the detailed statistical analysis plan, methods for handling missing observations, outcome-specific analysis populations beyond the primary endpoint description, or estimates of uncertainty for the primary result. It lists eight outcome measures and zero analyses. These omissions limit assessment of how the planned analyses were implemented and how complete the outcome reporting is. They do not establish that analyses were not performed; they indicate that analysis results are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists eight outcome measures, including the Phase I best overall response measure and several Phase I and Phase II outcomes relating to overall survival, time to progression, stable disease, and response. It reports zero analyses. Results for these outcomes are not reported in the registry record, and no multiplicity procedure is reported there.
Multiplicity arises when several outcomes or statistical tests are considered. General statistical principle: the more questions tested, the greater the chance of a false-positive finding if each test is interpreted without accounting for the set of tests. A prespecified hierarchy, adjustment, or clear distinction between primary and exploratory outcomes can help readers understand how multiple results were handled. The registry record does not report these details, so no claim can be made about whether or how multiplicity was controlled.
The primary endpoint description specifies an MTD-determining population: patients who completed Cycle 1 according to protocol or discontinued due to a DLT. The record does not report the size of that population, missing endpoint data, or a method for handling missing observations. It also does not report analysis populations for the listed secondary outcomes. Accordingly, the completeness of outcome ascertainment and the relationship between enrolled participants and analyzed populations cannot be assessed from the registry record.
These reporting gaps do not imply that data were missing or that analyses were omitted in the conduct of the study. They mean the registry record does not provide enough information to evaluate those issues. The MTD statement can be interpreted according to the protocol rule described, while the unavailable analysis and missing-data details remain limitations on broader statistical interpretation.
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 |
|---|---|---|---|
| Patupilone ≤7.0 mg/m^2 (Phase I) | 3 | 6 | 50.0% |
| Patupilone 7.5-8.0 mg/m^2 (Phase I) | 3 | 12 | 25.0% |
| Patupilone 8.5-9.5 mg/m^2 (Phase I) | 2 | 12 | 16.7% |
| Patupilone 10.0-11.5 mg/m^2 (Phase I) | 3 | 12 | 25.0% |
| Patupilone 12.0-13.0 mg/m^2 (Phase I) | 4 | 8 | 50.0% |
| Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort | 14 | 35 | 40.0% |
| Patupilone 10 mg/m^2 (Phase II) NSCLC w. Brain Metastases (BM) | 2 | 4 | 50.0% |
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 |
|---|---|
| Patupilone ≤7.0 mg/m^2 (Phase I) | 6 of 6 |
| Patupilone 7.5-8.0 mg/m^2 (Phase I) | 11 of 12 |
| Patupilone 8.5-9.5 mg/m^2 (Phase I) | 12 of 12 |
| Patupilone 10.0-11.5 mg/m^2 (Phase I) | 10 of 12 |
| Patupilone 12.0-13.0 mg/m^2 (Phase I) | 8 of 8 |
| Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort | 33 of 35 |
Most frequent serious adverse event terms
| Event term | Organ system | Patupilone ≤7.0 mg/m^2 (Phase I) | Patupilone 7.5-8.0 mg/m^2 (Phase I) | Patupilone 8.5-9.5 mg/m^2 (Phase I) | Patupilone 10.0-11.5 mg/m^2 (Phase I) | Patupilone 12.0-13.0 mg/m^2 (Phase I) | Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort |
|---|---|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 1 of 6 | 1 of 12 | 1 of 12 | 1 of 12 | 1 of 8 | 8 of 35 |
| Asthenia | General disorders | 1 of 6 | 0 of 12 | 0 of 12 | 0 of 12 | 1 of 8 | 1 of 35 |
| Pneumonia | Infections and infestations | 0 of 6 | 0 of 12 | 1 of 12 | 1 of 12 | 0 of 8 | 1 of 35 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 6 | 1 of 12 | 0 of 12 | 0 of 12 | 0 of 8 | 1 of 35 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 0 of 6 | 0 of 12 | 0 of 12 | 0 of 12 | 1 of 8 | 1 of 35 |
| Pericardial effusion | Cardiac disorders | 0 of 6 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 8 | 1 of 35 |
| Abdominal pain | Gastrointestinal disorders | 0 of 6 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 8 | 1 of 35 |
| Colitis | Gastrointestinal disorders | 0 of 6 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 8 | 1 of 35 |
| Enteritis | Gastrointestinal disorders | 0 of 6 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 8 | 1 of 35 |
| Intestinal obstruction | Gastrointestinal disorders | 0 of 6 | 0 of 12 | 0 of 12 | 0 of 12 | 0 of 8 | 1 of 35 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Patupilone ≤7.0 mg/m^2 (Phase I) | Patupilone 7.5-8.0 mg/m^2 (Phase I) | Patupilone 8.5-9.5 mg/m^2 (Phase I) | Patupilone 10.0-11.5 mg/m^2 (Phase I) | Patupilone 12.0-13.0 mg/m^2 (Phase I) | Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort |
|---|---|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 3 of 6 | 6 of 12 | 9 of 12 | 7 of 12 | 7 of 8 | 29 of 35 |
| Vomiting | Gastrointestinal disorders | 1 of 6 | 4 of 12 | 5 of 12 | 3 of 12 | 3 of 8 | 12 of 35 |
| Abdominal pain | Gastrointestinal disorders | 3 of 6 | 5 of 12 | 3 of 12 | 4 of 12 | 0 of 8 | 10 of 35 |
| Nausea | Gastrointestinal disorders | 3 of 6 | 3 of 12 | 4 of 12 | 5 of 12 | 3 of 8 | 6 of 35 |
| Fatigue | General disorders | 3 of 6 | 2 of 12 | 4 of 12 | 3 of 12 | 3 of 8 | 5 of 35 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 6 | 3 of 12 | 1 of 12 | 0 of 12 | 4 of 8 | 12 of 35 |
| Paraesthesia | Nervous system disorders | 2 of 6 | 1 of 12 | 3 of 12 | 3 of 12 | 2 of 8 | 8 of 35 |
| Asthenia | General disorders | 1 of 6 | 2 of 12 | 3 of 12 | 0 of 12 | 1 of 8 | 11 of 35 |
| Abdominal distension | Gastrointestinal disorders | 4 of 6 | 2 of 12 | 2 of 12 | 3 of 12 | 0 of 8 | 4 of 35 |
| Pyrexia | General disorders | 0 of 6 | 3 of 12 | 3 of 12 | 1 of 12 | 2 of 8 | 4 of 35 |
Serious events with the highest arm-level rate: vomiting (25.0%), fatigue (25.0%), oedema peripheral (25.0%), dehydration (25.0%), confusional state (25.0%).
The safety listing separates serious adverse events from other adverse events and presents affected and at-risk counts within each dose group or cohort. For example, in the Phase I group titled Patupilone ≤7.0 mg/m^2, the record lists 3 of 6 participants affected by serious adverse events and 6 of 6 affected by other adverse events. In the Phase II 10 mg/m^2 NSCLC cohort, it lists 14 of 35 affected by serious adverse events and 33 of 35 affected by other adverse events. These are descriptive counts, not comparative estimates.
The listed groups include multiple Phase I dose ranges and two Phase II cohorts. Since assignment was non-randomized, the groups are not like-for-like controls. Differences in counts across them cannot establish that dose or cohort caused a difference in risk. The adverse-event record does not provide an adjusted comparison, and deaths are not reported in the registry record.
The most frequently listed serious adverse-event terms are Vomiting, Fatigue, Oedema peripheral, Dehydration, and Confusional state, each at 25.0%; Diarrhoea is listed at 22.9%. The registry record does not provide further details about the denominator or method used for these term percentages. These figures describe the reported safety listings and should not be interpreted as DLT rates or as a complete account of all possible harms.
12. What the Result Does, and Does Not, Mean
The registry record supports a specific conclusion about the Phase I dose-escalation rule: no more than one DLT occurred at any explored dose level up to 13 mg/m^2 during the stated assessment, and the protocol-defined MTD was not reached. This is the principal result available for the primary endpoint. It describes what was observed in the study's MTD-determining population under the protocol's definition.
That conclusion does not establish the toxicity rate beyond the observed participants, identify a safe dose for other settings, or show what would have happened at doses beyond those explored. It also does not mean that no adverse events occurred. The adverse-event listings report serious and other adverse events across the study's dose groups and cohorts. DLTs are a particular protocol endpoint and should not be treated as interchangeable with every adverse event.
The registry's study objective included safety and efficacy, and the record lists secondary outcomes for response and time-to-event measures. However, their results are not reported in the registry record. The available information therefore does not establish an effect on tumor response, survival, progression, or duration of response. An objective or an outcome listed for a study is not evidence of a result.
The study was non-randomized, open-label, and single-group. Its dose groups do not provide randomized controls. Observed differences among the cohorts may reflect their composition or other factors, so they cannot be attributed to dose or treatment through a controlled comparison. The record also provides no inferential analyses or uncertainty estimates for the primary endpoint.
In statistical terms, the result is best read as a protocol-specific descriptive finding from dose escalation. It is informative about whether the stated MTD rule was met within the explored dose levels, but not a precise estimate of toxicity risk, a comparative treatment effect, or a complete assessment of efficacy. Those distinctions are important when interpreting the registry's safety counts and its unreported secondary outcomes.
13. Why This Trial Matters Statistically
This trial illustrates how a dose-escalation endpoint differs from the outcomes commonly used to compare treatments. The primary question was whether observed DLT counts met a protocol-defined threshold for identifying the MTD. The registry says that threshold was not reached through the explored dose levels up to 13 mg/m^2. That is a decision-rule result, not a finding from a randomized comparison.
It also shows why the analysis population must be understood alongside the endpoint. The MTD determination used first-cycle data from patients who completed the cycle according to protocol or discontinued due to a DLT. The enrolled population and the endpoint-specific population need not be identical, and the registry record does not report the size of the latter. Without that detail, readers cannot fully assess the precision of the reported dose-escalation experience.
The safety listings further illustrate the limits of descriptive comparisons. Serious and other adverse events are listed across dose groups and cohorts, but allocation was non-randomized. The group counts can describe the recorded experience; they cannot isolate a causal dose effect or serve as a controlled estimate of comparative risk.
Finally, the record lists response and time-to-event outcomes but does not report their results or analyses. This distinction between outcomes named in a registry and results available for interpretation is central to statistical reading. The study offers a reported primary dose-escalation conclusion, while efficacy questions and several analytical details remain unresolved in the registry record.
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 result is reported as a protocol conclusion rather than as a dose-specific estimate with uncertainty. The registry record does not provide confidence intervals, a model-based toxicity estimate, or further detail about the number of patients contributing to the MTD determination. This restricts assessment of precision.
The trial was non-randomized, open-label, and single-group. There was no randomized control group, so neither the safety listings nor the dose cohorts can support a like-for-like comparative treatment effect. The registry record also does not report adjusted analyses that might address differences among cohorts.
The Phase I endpoint is limited to DLTs assessed during Cycle 1. The record does not report how later toxicities informed safety conclusions or provide detailed DLT criteria beyond the endpoint description. The broad adverse-event listings are not a substitute for the primary endpoint because the record does not say that all listed events met DLT criteria.
Although secondary outcomes are listed, their results are not reported in the registry record. Statistical analysis methods, missing-data handling, multiplicity procedures, and analysis populations for those outcomes are also not reported in the registry record. The absence of these details limits evaluation of the efficacy outcomes and of the completeness of reporting. The record does not report a sample-size justification, so the basis for the enrollment target cannot be assessed.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Dose Escalating Study of the Safety and Efficacy of Patupilone, q3w, in Patients With Non-small Cell Lung Cancer — NCT00171834.
- Registry record last updated 2014-02-05; status last verified 2014-01.
- Results first posted 2011-07-07.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record describes a completed, open-label, non-randomized Phase I/II study of patupilone in non-small cell lung cancer, sponsored by Novartis Pharmaceuticals. Enrollment was 89. The study began in 2003-08, with primary completion in 2008-09. Its objective was to evaluate MTD, safety, and efficacy in patients whose disease had progressed after prior chemotherapy.
The Phase I primary endpoint counted DLTs during Cycle 1 to determine the MTD under a stated 3+3 rule. The record reports no more than one DLT at any explored dose level up to 13 mg/m^2 and states that the protocol-defined MTD was not reached. Serious and other adverse-event counts are listed by dose group or cohort. The record lists secondary response and time-to-event outcomes, but their results and analyses are not reported in the registry record.