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 Ph I/II Nab-Paclitaxel & Carboplatin w/Concurrent Radiation Therapy for Unresectable Stg III NSCLC (NCT00544648), a na phase 1, phase 2 study. The primary outcome is Maximum Tolerated Dose of Nab-paclitaxel When Combined Concurrently With Carboplatin and Radiation (Phase I).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00544648 |
| Phase | Phase 1, Phase 2 |
| Condition | Lung Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 13 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Vanderbilt-Ingram Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients with stage III non-small-cell lung cancer that could not be removed by surgery. The registry record says one patient withdrew before receiving treatment; it does not provide further eligibility details in the posted primary-outcome description.
Intervention
Nab-paclitaxel and carboplatin given concurrently with radiation therapy. The trial was designed to study tolerability and dose, as well as response and survival outcomes. Specific schedules beyond concurrent treatment are not reported in the registry record.
Comparator
There was no separate control group: the design is listed as single-group, with no allocation to a comparator. The results therefore do not provide a randomized, like-for-like comparison with another treatment or with no treatment.
Primary question
In Phase I, what was the highest dose of nab-paclitaxel that could be combined with carboplatin and radiation therapy while meeting the trial’s tolerability rule? The rule defined the maximum tolerated dose as the dose before one at which 2 or more of 6 patients experienced a dose-limiting toxicity during the initial cycle. The numerical dose achieved is not reported in the registry record.
3. Trial Design
This was a Phase I/II, single-group study of nab-paclitaxel, carboplatin and concurrent radiation therapy for unresectable stage III non-small-cell lung cancer. The listed allocation is not applicable, and masking is listed as none. With no control group, the design can describe outcomes among treated participants but cannot make a randomized comparison against another regimen.
The registry record lists enrollment of 13 and a terminated status. The study start is recorded as 2007-11 and primary completion as 2014-04. The reason for termination is not reported in the registry record. These administrative details do not establish why the study ended or what outcomes were observed.
The Phase I dose-finding description says cohorts of 3-6 patients received escalating nab-paclitaxel doses with carboplatin until the maximum tolerated dose was achieved. The stated endpoint was the highest dose that met the tolerability rule. One patient withdrew before receiving study treatment, and the primary-outcome population is described as patients who received the study drug. Further details about dose levels, cohort decisions, treatment delivery, or the transition between phases are not reported in the registry record.
Phase I and Phase II outcomes listed include response, overall survival and toxicity; progression-free survival is listed for Phase I. The registry record reports 10 outcome measures and 0 analyses. It does not provide a numerical primary endpoint result or formal statistical analysis results.
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: Twenty-two patients signed consent on this study, nine of which were ineligible to receive treatment.
Overall Study
| Stage | Phase I | Phase II |
|---|---|---|
| STARTED | 11 | 2 |
| COMPLETED | 8 | 1 |
| NOT COMPLETED | 3 | 1 |
Reasons for not completing this period:
| Reason | Phase I | Phase II |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
| Adverse Event | 1 | 1 |
| progression of disease | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: MTD based on clinical performance of those patients who received the study drug. One patient withdrew before receiving treatment. No formal statistical analysis, such as hypothesis testing, was performed.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Consented patients
| Characteristic | Unit | Phase I | Phase II | Total |
|---|---|---|---|---|
| Participants analysed | 11 | 2 | 13 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 | 2 | 6 |
| Age, Categorical: >=65 years | Participants | 7 | 0 | 7 |
| Age, Continuous | years | 63 (SD 9) | 56 (SD 4) | 59 (SD 16) |
| Sex: Female, Male: Female | Participants | 2 | 1 | 3 |
| Sex: Female, Male: Male | Participants | 9 | 1 | 10 |
| Region of Enrollment: United States | participants | 11 | 2 | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose of Nab-paclitaxel When Combined Concurrently With Carboplatin and Radiation (Phase I), measured over 7 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg/m2 |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the maximum tolerated dose of nab-paclitaxel when combined concurrently with carboplatin and radiation therapy in Phase I. It was expressed in mg/m2 and assessed over 7 weeks. The endpoint was intended to identify a dose that could be administered while satisfying the trial’s specified toxicity rule, rather than to compare the regimen with a control treatment.
The protocol description defines the maximum tolerated dose as the dose preceding the dose at which 2 or more of 6 patients experience dose-limiting toxicity during the initial cycle. The listed dose-limiting toxicities include recurring non-hematological toxicity, with esophagitis treated separately, and toxicity that is symptomatically unacceptable and results in a treatment delay for > 2 weeks. Persistent toxicity resulting in a treatment delay for > 2 weeks is also included. The grading thresholds are described using Common Toxicity Criteria v 3.0.
Dose-finding endpoints are used to guide selection of a dose for further study under a prespecified tolerability rule. The registry record does not report the achieved maximum tolerated dose, the dose levels tested, or which cohort triggered the stopping rule. It also states that no formal statistical analysis, such as hypothesis testing, was performed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a small, single-group Phase I/II trial, with enrollment of 13 and a terminated status. Its primary endpoint was a Phase I dose-finding measure, not a randomized estimate of treatment benefit. Although the endpoint definition and escalation rule are described, the numerical maximum tolerated dose is not reported in the registry record. As a result, the posted information does not establish which nab-paclitaxel dose met the rule.
The record also lists response, survival and toxicity outcomes, but reports 0 analyses. The outcomes named in the record therefore indicate what was intended for assessment, not that results for each outcome are available. No response estimate, survival estimate, confidence interval, or hypothesis-test result is reported in the registry record. The absence of a reported estimate is not evidence that an outcome was zero or that there was no effect.
Safety information is presented separately for Phase I and Phase II. For Phase I, 10 participants were at risk for serious adverse events and 5 were affected; 10 were at risk for other adverse events and 10 were affected. For Phase II, 2 participants were at risk for serious adverse events and 1 was affected; 2 were at risk for other adverse events and 2 were affected. These are counts within the posted registry categories. They do not establish how many events occurred per participant, whether participants experienced both categories, or how toxicity compared with an alternative regimen. Those details are not reported in the registry record.
The listed serious-event terms include sinus tachycardia, probably related to pneumonia; pain-chest, thorax NOS; dyspnea; tachypnea, probably related to pneumonia; neutrophils; and platelets. Percentages are reported for these terms, but the registry record does not describe the denominators or clarify whether terms refer to participants or event occurrences. They should therefore be read as the registry’s listed term-level figures, not as a basis for deriving unreported risks.
In general, a confidence interval describes the uncertainty around an estimated quantity. No confidence interval is reported for the primary endpoint or efficacy outcomes, so precision cannot be assessed from interval estimates. The small at-risk counts and lack of a comparator further limit what can be concluded from the posted counts. The registry record does not report why the trial was terminated.
9. Statistical Methods Explained
The registry describes a Phase I/II study with a single-group model. The treatment combined nab-paclitaxel, carboplatin and radiation therapy. Allocation is listed as not applicable and masking as none. These features matter when interpreting the results: there is no concurrent control arm to separate treatment-associated outcomes from other influences, and participants or study staff were not masked according to the record.
How does the Phase I dose-finding rule work?
The Phase I description says cohorts of 3-6 patients received escalating nab-paclitaxel doses with carboplatin until the maximum tolerated dose was achieved. The stated rule defines that dose as the dose preceding one at which 2 or more of 6 patients experience a dose-limiting toxicity during the initial cycle. The rule uses observed toxicity to guide escalation and identify a dose for further study; it is not a test of whether the regimen improves survival or response.
The listed dose-limiting toxicity criteria refer to Common Toxicity Criteria v 3.0. They include recurring non-hematological toxicity, with an exception for esophagitis in one criterion; non-hematological toxicity or esophagitis that is symptomatically unacceptable and leads to a treatment delay for > 2 weeks; and persistent toxicity leading to a treatment delay for > 2 weeks. The registry record does not report which toxicities occurred during dose escalation, how the criteria were applied to individual participants, or the resulting dose decision.
What does the endpoint measure?
The primary endpoint is a dose, expressed in mg/m2, and the assessment timeframe is 7 weeks. It measures the dose selected under the stated tolerability definition. It is distinct from an estimate of response or survival. The endpoint description says the maximum tolerated dose was based on the clinical performance of participants who received study drug. One patient withdrew before receiving treatment. The numerical endpoint value and further details about the analysis population are not reported in the registry record.
What is the role of formal statistical analysis?
The primary-outcome description explicitly says no formal statistical analysis, such as hypothesis testing, was performed. The registry record lists 10 outcome measures and 0 analyses. It does not report inferential estimates, confidence intervals, or p-values for the primary endpoint or listed efficacy outcomes. In general, hypothesis tests assess how compatible data are with a specified null hypothesis, while confidence intervals communicate uncertainty around an estimate. Neither type of result is available for the primary endpoint in the record.
The design is single-group, so the results cannot be interpreted as a randomized treatment contrast. In general, a comparator helps distinguish outcomes associated with a treatment from changes that might occur for other reasons. Without that comparison, observed events and outcomes describe the enrolled group and do not estimate what would have happened to the same participants under an alternative regimen.
How should the planning assumptions be understood?
The registry record describes sample-size illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a specified fraction of the observed effect. For time-to-event outcomes, the illustrations concern total events; for other outcomes, they concern participants per arm. These are planning illustrations, not observed trial results or observed power. The registry record does not report a numerical observed effect or numerical planning results, so no particular planning figure can be interpreted from the posted information.
In general, over-dispersion means that outcome variability is greater than a model assumes. It can make uncertainty estimates too narrow if the extra variability is not accounted for. The record does not report an over-dispersion analysis, and no such result should be inferred from the listed safety counts. The registry also does not report the detailed statistical model, analysis choices for secondary endpoints, or any adjustment for baseline characteristics.
10. Multiplicity, Missing Data and Analysis Populations
The record lists several secondary outcomes: progression-free survival, overall survival, response and worst-grade toxicity, with some outcomes specified separately for Phase I and Phase II. It also lists a primary Phase I maximum tolerated dose endpoint. When multiple outcomes are examined, the chance of at least one apparently unusual result can increase if each is tested independently. In general, multiplicity methods can control or describe that issue, but the registry record does not report a multiplicity plan or adjustment.
The record reports 10 outcome measures and 0 analyses. No formal hypothesis testing is described for the primary endpoint, and statistical methods for the listed secondary outcomes are not reported in the registry record. It is therefore not possible to assess whether analyses were prespecified, whether any outcomes were omitted from analysis, or how any multiple comparisons were handled.
One patient withdrew before receiving treatment. The record says the maximum tolerated dose was based on clinical performance among patients who received study drug, but does not describe a broader analysis population for other outcomes. Missing-data methods, reasons for missing outcome measurements, follow-up completeness, and any imputation procedures are not reported in the registry record. Nor does it describe whether outcome-specific denominators differed from the safety counts.
These omissions affect interpretation: the posted record does not allow an assessment of whether missing observations could have influenced outcome estimates, or whether the analysis populations were defined consistently across outcomes. No outcome estimates are reported with which to evaluate that uncertainty.
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 |
|---|---|---|---|
| Phase I | 5 | 10 | 50.0% |
| Phase II | 1 | 2 | 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 |
|---|---|
| Phase I | 10 of 10 |
| Phase II | 2 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase I | Phase II |
|---|---|---|---|
| neutrophils | Blood and lymphatic system disorders | 4 of 10 | 0 of 2 |
| platelets | Blood and lymphatic system disorders | 3 of 10 | 0 of 2 |
| thrombosis | Vascular disorders | 2 of 10 | 0 of 2 |
| hypoxia | Respiratory, thoracic and mediastinal disorders | 2 of 10 | 0 of 2 |
| hemoglobin | Blood and lymphatic system disorders | 1 of 10 | 0 of 2 |
| radiation dermatitis | Skin and subcutaneous tissue disorders | 1 of 10 | 0 of 2 |
| hyponatremia | Metabolism and nutrition disorders | 1 of 10 | 0 of 2 |
| febrile neutropenia | Blood and lymphatic system disorders | 1 of 10 | 0 of 2 |
| digoxin toxicity | Cardiac disorders | 1 of 10 | 0 of 2 |
| sore throat | Respiratory, thoracic and mediastinal disorders | 1 of 10 | 0 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase I | Phase II |
|---|---|---|---|
| hemoglobin | Blood and lymphatic system disorders | 10 of 10 | 2 of 2 |
| fatigue | General disorders | 9 of 10 | 2 of 2 |
| hyperglycemia | Metabolism and nutrition disorders | 10 of 10 | 1 of 2 |
| hypomagnesemia | Metabolism and nutrition disorders | 7 of 10 | 1 of 2 |
| cough | Respiratory, thoracic and mediastinal disorders | 6 of 10 | 1 of 2 |
| nausea | Gastrointestinal disorders | 4 of 10 | 2 of 2 |
| leukocytes (total WBC) | Blood and lymphatic system disorders | 4 of 10 | 1 of 2 |
| platelets | Blood and lymphatic system disorders | 4 of 10 | 1 of 2 |
| constitutional symptoms-other | General disorders | 4 of 10 | 1 of 2 |
| dyspnea | Respiratory, thoracic and mediastinal disorders | 5 of 10 | 0 of 2 |
Serious events with the highest arm-level rate: sinus tachycardia, probably related to pneumonia (50.0%), pain-chest, thorax nos (50.0%), dyspnea (50.0%), tachypnea, probably related to pneumonia (50.0%), neutrophils (40.0%).
The registry separates serious adverse events from other adverse events and reports counts at risk and affected for each phase. In Phase I, 10 participants were at risk for serious adverse events and 5 were affected; 10 were at risk for other adverse events and 10 were affected. In Phase II, 2 participants were at risk for serious adverse events and 1 was affected; 2 were at risk for other adverse events and 2 were affected. These counts should be read within the registry’s phase categories, not as a comparison between treatments.
The listed serious-event terms have associated percentages: sinus tachycardia, probably related to pneumonia; pain-chest, thorax NOS; dyspnea; and tachypnea, probably related to pneumonia are each listed as 50.0%; neutrophils is listed as 40.0%; and platelets as 30.0%. The denominator and counting rule for these term-level percentages are not reported in the registry record. The terms may not represent mutually exclusive participants, and the figures do not show how many events each participant experienced.
Deaths are not reported in the registry record. Without event-level detail, duration of exposure, or a comparator, the counts cannot establish comparative safety or the cause of an event.
12. What the Result Does, and Does Not, Mean
The posted information describes a Phase I/II, single-group evaluation of nab-paclitaxel with carboplatin and concurrent radiation therapy in unresectable stage III non-small-cell lung cancer. It gives a Phase I dose-escalation framework and a definition of dose-limiting toxicity. It also reports phase-specific counts of participants at risk for, and affected by, serious and other adverse events.
The record does not report the numerical maximum tolerated dose. It also does not report formal analysis results for response, progression-free survival, overall survival, or toxicity beyond the posted safety counts and serious-event terms. The record’s list of outcomes should not be mistaken for a set of reported estimates. Likewise, the terminated status does not explain why the trial ended; a reason is not reported in the registry record.
In general, a single-group study can characterize outcomes observed among treated participants, but it cannot provide a randomized comparison against a control group. The listed safety counts consequently do not establish whether the regimen produced more or fewer adverse events than another treatment. No claim about comparative efficacy or safety can be drawn from the posted record.
The sample-size material is described as planning illustration, not as observed power. The record does not report numerical planning results or an observed effect to interpret. The available information therefore supports a description of the trial’s intended dose-finding question and its recorded safety counts, but not a quantitative conclusion about treatment effects or precision.
13. Why This Trial Matters Statistically
This trial illustrates why the endpoint definition and the reported endpoint value need to be considered separately. The registry gives a specific Phase I rule for selecting a maximum tolerated dose, including cohort escalation and a dose-limiting toxicity threshold. But it does not report the dose ultimately selected. A clear method is useful for understanding what investigators intended to measure; without the result, it does not answer the dose-finding question.
The record also distinguishes a Phase I/II study’s dose-finding aim from outcomes such as response and survival. These outcomes answer different questions and require outcome-specific information. The registry lists multiple measures but reports 0 analyses, so the listed aims should not be confused with numerical findings. This is especially important when a record includes a mixture of endpoint descriptions and safety counts.
The single-group design is another key statistical feature. Without a concurrent comparator, observed outcomes do not estimate a randomized contrast. This is not remedied by the presence of several outcome measures or by a detailed toxicity rule; each addresses a different aspect of the study question.
Finally, the safety counts show why denominators and definitions matter. Phase-specific counts indicate how many participants were at risk and affected in the posted categories, while the serious-event terms carry percentages whose denominator is not reported. Keeping those distinctions visible prevents the registry’s term-level figures from being treated as more precise or comparative estimates than the record supports.
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 has several limitations for statistical interpretation. It does not report the numerical maximum tolerated dose, despite describing the Phase I dose-escalation rule. It also does not report dose levels tested, the cohort-by-cohort decisions, or the individual dose-limiting toxicities that informed dose selection. The reason for termination is not reported.
The study was single-group, with no randomized comparator. Thus, the record cannot support a direct treatment comparison. Enrollment was 13, and the safety counts show small numbers at risk in the phase-specific categories. The record does not provide confidence intervals or other estimates of precision for the primary endpoint or efficacy outcomes.
Although response, progression-free survival, overall survival and toxicity outcomes are listed, formal analyses are not reported. The record does not describe the analysis methods for secondary outcomes, multiplicity handling, follow-up completeness, missing-data procedures, or outcome-specific analysis populations. One patient withdrew before receiving treatment, but further details about withdrawal or the handling of other missing information are not reported.
The serious-event terms are accompanied by percentages, but the registry record does not state their denominators or counting rules. It also does not report deaths. These gaps limit interpretation of the term-level figures and prevent a complete account of the safety experience. The posted information therefore supports a description of trial design, endpoint definition and registry safety counts, but not a comprehensive statistical evaluation of efficacy, comparative safety, or precision.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Ph I/II Nab-Paclitaxel & Carboplatin w/Concurrent Radiation Therapy for Unresectable Stg III NSCLC — NCT00544648.
- Registry record last updated 2014-06-09; status last verified 2014-05.
- Results first posted 2014-06-09.
- 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
NCT00544648 is a terminated Phase I/II, single-group study of nab-paclitaxel and carboplatin with concurrent radiation therapy for unresectable stage III non-small-cell lung cancer. Enrollment was 13. The primary Phase I endpoint was the maximum tolerated dose of nab-paclitaxel under a specified dose-limiting toxicity rule. Its numerical result is not reported in the registry record.
The record lists 10 outcome measures and 0 analyses, and states that no formal statistical analysis, such as hypothesis testing, was performed for the primary endpoint. It reports phase-specific counts for serious and other adverse events, and lists serious-event terms with percentages. The denominators for those percentages, deaths, the reason for termination, and formal efficacy results are not reported in the registry record.