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 Phase I/II Calcitriol in Lung Cancer (NCT00794547), a non-randomized phase 1, phase 2 study. The primary outcome is MTD of Intravenous Calcitriol When Administered Prior to Fixed Dose Cisplatin 75mg/m2 and Docetaxel 75 mg/m2, Every 3 Weeks in Patients With Advanced Non-small Cell Lung Cancer (NSCLC).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00794547 |
| Phase | Phase 1, Phase 2 |
| Condition | Non Small Cell Lung Cancer |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 34 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Michigan Rogel Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
People with advanced non-small cell lung cancer (NSCLC). The primary outcome description says eighteen patients were enrolled for the toxicity assessment, with sixteen evaluable; two were not evaluable because their disease progressed before completing cycle one.
Intervention
Intravenous calcitriol given before fixed-dose cisplatin 75mg/m2 and docetaxel 75 mg/m2, administered every 3 weeks. The Phase I objective was to determine the maximum tolerated dose of calcitriol. The Phase II description refers to a fixed calcitriol dose determined in Phase I, but the selected dose is not reported in the registry record.
Comparator
There was no separate control group: the study is described as non-randomized and single-group, with no masking. Consequently, it does not make a like-for-like comparison against another treatment or against a control group receiving the chemotherapy without calcitriol.
Primary question
What is the maximum tolerated dose of intravenous calcitriol when administered before the specified cisplatin and docetaxel regimen in advanced NSCLC? The registry record states this objective, but the dose identified as the maximum tolerated dose and the supporting toxicity results are not reported in the registry record.
3. Trial Design
This is a Phase I/II, non-randomized, unmasked, single-group clinical trial sponsored by the University of Michigan Rogel Cancer Center. The condition is non-small cell lung cancer. The registry lists enrollment of 34 participants. The recorded study start is 2008-12, the primary completion is 2011-10, and the status is terminated; the reason for termination is not reported in the registry record.
The Phase I objective was to determine the maximum tolerated dose of intravenous calcitriol given before fixed-dose cisplatin and docetaxel. The chemotherapy doses are stated as cisplatin 75mg/m2 and docetaxel 75 mg/m2, every 3 weeks. The Phase II description refers to assessing cancer response with a fixed calcitriol dose determined in Phase I. The actual calcitriol dose and detailed Phase II response results are not reported in the registry record.
The record's primary outcome description says eighteen patients were enrolled and sixteen were evaluable for toxicity assessment. Two were not evaluable because they progressed before completing cycle one. This differs from the overall enrollment figure of 34, and the record does not explain the relationship between these figures. The study's single-group structure means there is no concurrent control arm for separating the treatment combination's effects from other influences. It also means that the trial cannot provide a randomized comparison of calcitriol plus chemotherapy against the chemotherapy regimen alone.
The registry describes an accrual duration of 5 years in the primary outcome text, while its status is terminated. The reason for termination, dose-finding procedure, dose levels tested, and basis for the fixed Phase II dose are not reported in the registry record. The design and posted information therefore identify the trial's objectives and treatment combination, but do not establish what dose was selected or what response was observed.
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 | Phase 1 | Phase 2 |
|---|---|---|
| STARTED | 18 | 16 |
| COMPLETED | 18 | 16 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Eighteen patients were enrolled, and 16 were evaluable for toxicity assessments. Two patients were not evaluable as they progressed prior to completion of cycle 1.
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: Thirty-four patients were enrolled (18 in phase I and 16 in phase II).
| Characteristic | Unit | Calcitriol + Cisplatin + Docetaxel |
|---|---|---|
| Participants analysed | 34 | |
| Age, Continuous | years | 54 (34 to 79) |
| Sex: Female, Male: Female | Participants | 22 |
| Sex: Female, Male: Male | Participants | 12 |
| Region of Enrollment: United States | participants | 34 |
| Histology: Adenocarcinoma | participants | 21 |
| Histology: Squamous carcinoma | participants | 12 |
| Histology: NSCLC NOS | participants | 1 |
| Performance Status: Performance Status 0 | participants | 16 |
| Performance Status: Performance Status 1 | participants | 18 |
| Smoking Status: Never Smoker | participants | 2 |
| Smoking Status: Ever Smoker | participants | 29 |
| Smoking Status: Unknown | participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as MTD of Intravenous Calcitriol When Administered Prior to Fixed Dose Cisplatin 75mg/m2 and Docetaxel 75 mg/m2, Every 3 Weeks in Patients With Advanced Non-small Cell Lung Cancer (NSCLC), measured over 5 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mcg/m^2 |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is framed as the maximum tolerated dose (MTD) of intravenous calcitriol administered before cisplatin and docetaxel in people with advanced NSCLC. Its stated unit is mcg/m^2, and the outcome is categorized as a number. The MTD is a dose-finding endpoint: in general, it seeks to identify a dose that meets a study's prespecified tolerability criteria. Such a measure is used in early-phase research to guide dose selection for further evaluation, rather than to quantify a treatment's comparative benefit.
The registry record does not describe the toxicity criteria used to define the MTD, the dose levels assessed, the dose-escalation procedure, or the MTD result. It gives a timeframe of 5 years, and the outcome description also says the accrual duration was 5 years; the assessment schedule is not reported in the registry record. The outcome population description says eighteen patients were enrolled and sixteen were evaluable for toxicity, with two excluded from that assessment after progression before completing cycle one. These details help define the population described for the endpoint, but do not supply the endpoint value.
The Phase II description concerns cancer response with a fixed calcitriol dose determined during Phase I. Response is not the primary endpoint described in the posted outcome information. A response definition, response count, estimate, and uncertainty measure are not reported in the registry record. The MTD objective and the Phase II response objective should therefore be kept distinct: the former concerns dose and toxicity, while the latter concerns cancer response.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a dose-finding objective but does not report the resulting maximum tolerated dose. It also does not provide a primary endpoint estimate, a confidence interval, or an inferential test for that outcome. The posted information therefore cannot establish which calcitriol dose met the study's MTD criterion or how precisely that dose was estimated. The absence of a reported estimate is not evidence that a particular dose was or was not tolerated.
The record lists overall enrollment of 34, while the primary outcome description reports eighteen enrolled and sixteen evaluable for toxicity, with two not evaluable because they progressed before completing cycle one. The relationship between these population figures is not explained. They should not be silently treated as the same analysis population. The adverse-event record uses 34 participants at risk for both serious and other adverse events. That population count is distinct from the endpoint description's toxicity-evaluable count, and the record does not explain how the populations were assembled or reconciled.
The safety information reports that 20 of 34 participants were affected by serious adverse events and that 34 of 34 were affected by other adverse events. The listed serious adverse-event terms and percentages describe events recorded in the registry, but the record does not provide event-level timing, severity grades, attribution, or a comparison group. The counts cannot show whether an event was caused by calcitriol, cisplatin, docetaxel, the underlying illness, or another factor. Nor do they establish a relative safety profile against an alternative regimen.
The study is single-group and non-randomized, so it does not yield a randomized treatment contrast. The Phase II description mentions cancer response, but response results and their analysis are not reported in the registry record. Without a reported response estimate or comparator, no conclusion about the magnitude of response attributable to the combination can be drawn from these entries. More broadly, the posted information supports a description of the trial's objectives, design, enrollment fields, and recorded adverse events; it does not provide the endpoint results needed to evaluate the primary dose-finding question or the Phase II response objective.
Any planning illustration based on an observed effect should not be mistaken for an observed power calculation or for evidence of a treatment effect. The record describes a planning illustration using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects defined as fractions of an observed effect. Those assumptions are not the design of this single-group trial and do not create a valid randomized comparison where none was conducted. Numerical planning outputs or an observed effect are not reported in the registry record.
9. Statistical Methods Explained
What does the design allow?
The trial is described as non-randomized, unmasked, and single-group. These terms indicate that participants were not assigned by random allocation between comparison arms, that masking was absent, and that the registered model has one group. General statistical interpretation: random allocation can help balance measured and unmeasured participant characteristics across groups, while masking can reduce some influences on assessment and reporting. Neither feature is present. This does not invalidate the descriptive information, but it limits the kinds of treatment comparisons the design can support.
With a single group, outcomes describe what occurred among participants receiving the recorded treatment combination. They do not by themselves estimate what would have occurred for comparable participants under a different treatment. Changes in health, disease course, concomitant care, and assessment can contribute to observed outcomes. Without a concurrent control group, those influences cannot be separated from the treatment combination by a randomized between-group contrast. The Phase II description indicates an interest in cancer response, but the response results are not reported in the registry record.
What does an MTD endpoint mean?
In general, a maximum tolerated dose endpoint is used in early-phase dose-finding research. It depends on operational rules that define which toxicities count, the period in which they are assessed, and how observed toxicity informs dose selection. Different rules can lead to different dose decisions, so reporting the procedure and criteria is important for interpreting an MTD. The registry record states the MTD objective and gives the endpoint unit as mcg/m^2, but the dose levels, toxicity criteria, dose-selection algorithm, and selected MTD are not reported in the registry record.
The record says that sixteen patients were evaluable for toxicity and that two patients were not evaluable because they progressed before completing cycle one. This identifies a reason for non-evaluability, but it does not describe whether or how those participants were included in any other analysis. General statistical interpretation: excluding participants from a toxicity assessment can affect the interpretation of a dose-finding result, particularly if exclusions are associated with early events or differing exposure. Understanding the impact requires a clear analysis-population definition and a report of how all enrolled participants were handled. Those details are not reported in the registry record.
How should uncertainty be assessed?
A confidence interval is a general statistical tool for describing the precision of an estimate under a specified analysis. A narrow interval indicates greater precision than a wide interval, but neither the interval nor the underlying primary endpoint estimate is reported for this trial. A p-value, if reported, would address compatibility of data with a specified statistical model or null hypothesis; it would not by itself quantify clinical importance or establish causation. No analysis records are listed, and no primary endpoint test or interval is reported in the registry record.
General statistical interpretation: dose-finding outcomes are often best understood through the observed toxicity pattern across tested doses, together with the dose-selection rule and uncertainty in the estimated toxicity. A single selected MTD can conceal how much evidence supports that choice. The registry entry does not report the toxicity pattern by dose, the number treated at each dose, or an uncertainty analysis. It is therefore not possible to reconstruct or assess the dose-finding process from the posted result fields.
What is over-dispersion?
Over-dispersion is a general issue that arises when count data vary more than a statistical model assumes. If a model underestimates that variation, standard errors may be too small and intervals or tests may appear more certain than warranted. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report a count model, a fitted statistical model, or a dispersion assessment, so no claim can be made that over-dispersion was present or addressed in this trial. The adverse-event counts should be read descriptively rather than as outputs from a documented model.
What does the planning illustration represent?
The planning illustration is described as a calculation based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Its effect scenarios are expressed as fractions of the observed effect. These are planning assumptions, not the trial's own design. In particular, equal allocation between two arms does not match the registered single-group design. Planning sample sizes based on such assumptions are illustrations for a hypothetical comparison, not participants actually enrolled in this study and not observed power. No numerical illustration outputs or observed effect are reported in the registry record.
General statistical interpretation: a sample-size calculation depends on the target effect, outcome variability, statistical test, allocation, significance level, and desired power. Changing those assumptions changes the planning result. A calculation does not demonstrate that the study had the calculated power, nor does it guarantee precision or a statistically significant result. Because the registry record does not report the trial's own sample-size justification or design assumptions, the planning illustration should not be treated as evidence about the rationale for enrolling the study population.
What can be concluded from the posted analyses?
The registry reports zero analysis records. It lists six outcome measures and names mean AUC 1,25-D3 Concentration at 12 and 24 Hours as a secondary outcome. Full details of the other measures, their analytic definitions, estimates, and uncertainty are not reported in the registry record. Without analysis methods and results, readers cannot determine whether outcome distributions were adjusted, how missing observations were handled, or whether any prespecified inferential procedure was followed. The general statistical concepts above explain what such methods can address; they do not imply that any particular method was used in this trial.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity plan describing how inference across outcomes, dose levels, or repeated assessments was handled. This matters in general because conducting multiple statistical tests can increase the chance of at least one apparently unusual result under a model in which no effects are present. A prespecified testing hierarchy or adjustment may address that issue, but neither should be assumed without documentation. The number of analysis records is zero, and inferential analyses are not described in the registry record.
Missing-data methods and rules for analysis populations are not reported in the registry record. The primary outcome description says eighteen patients were enrolled, sixteen were evaluable for toxicity, and two were not evaluable because they progressed before completing cycle one. The record does not explain how these participants were treated in analyses other than the stated toxicity assessment, or whether further observations were missing. Overall enrollment is listed as 34, and the relationship between that figure and the primary outcome population is not explained.
General statistical interpretation: excluding participants with incomplete assessments can alter the population represented by an estimate, especially if the reasons for missingness are related to disease progression, toxicity, or treatment exposure. A clear report would specify the analysis population for each outcome and describe how incomplete observations were handled. The registry record does not provide those details, so the effect of missingness on the reported safety or endpoint information cannot be assessed. No imputation method, sensitivity analysis, or intention-to-treat analysis is reported in the registry record.
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 |
|---|---|---|---|
| Calcitriol + Cisplatin + Docetaxel | 20 | 34 | 58.8% |
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 |
|---|---|
| Calcitriol + Cisplatin + Docetaxel | 34 of 34 |
Most frequent serious adverse event terms
| Event term | Organ system | Calcitriol + Cisplatin + Docetaxel |
|---|---|---|
| Dehydration | Gastrointestinal disorders | 3 of 34 |
| Diarrhea | Gastrointestinal disorders | 3 of 34 |
| Febrile neutropenia | Infections and infestations | 3 of 34 |
| Low Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | 2 of 34 |
| Supraventricular and nodal arrhythmia | Cardiac disorders | 2 of 34 |
| Hypotension | Cardiac disorders | 2 of 34 |
| Nausea | Gastrointestinal disorders | 2 of 34 |
| Vomiting | Gastrointestinal disorders | 2 of 34 |
| Lung Infection | Infections and infestations | 2 of 34 |
| Abdominal Pain | Gastrointestinal disorders | 1 of 34 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Calcitriol + Cisplatin + Docetaxel |
|---|---|---|
| Nausea | Gastrointestinal disorders | 21 of 34 |
| Fatigue | General disorders | 17 of 34 |
| Glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders | 17 of 34 |
| Anorexia | Gastrointestinal disorders | 15 of 34 |
| Low Hemoglobin | Blood and lymphatic system disorders | 14 of 34 |
| Low Leukocytes (total WBC) | Blood and lymphatic system disorders | 14 of 34 |
| Low Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | 14 of 34 |
| Sodium, serum-low (hyponatremia) | Metabolism and nutrition disorders | 14 of 34 |
| Vomiting | Gastrointestinal disorders | 12 of 34 |
| Lymphopenia | Blood and lymphatic system disorders | 11 of 34 |
Serious events with the highest arm-level rate: dehydration (8.8%), diarrhea (8.8%), febrile neutropenia (8.8%), low neutrophils/granulocytes (anc/agc) (5.9%), supraventricular and nodal arrhythmia (5.9%).
The registry lists 34 participants at risk for serious adverse events, with 20 affected, and 34 at risk for other adverse events, with 34 affected. These are participant counts in the posted safety record. They are not estimates of comparative risk because there is no control group. The record does not report deaths in the adverse-event fields.
The listed serious adverse-event terms are dehydration, diarrhea, and febrile neutropenia, each at 8.8%; low neutrophils/granulocytes (ANC/AGC) and supraventricular and nodal arrhythmia, each at 5.9%; and hypotension at 5.9%. These are the recorded percentages for the listed terms. The registry does not clarify in this entry whether participants could contribute to multiple terms, and the listed percentages should not be added together to estimate the proportion with any serious event.
General statistical interpretation: an adverse event recorded during a trial is not necessarily caused by the study treatment. Attribution, event timing, severity grading, exposure duration, and the basis for counting recurrent events are not reported in the registry record. The safety counts therefore describe recorded events in the study group; without those details or a comparator, they do not establish comparative safety or causation.
12. What the Result Does, and Does Not, Mean
The posted information establishes that the trial was designed as a Phase I/II evaluation of intravenous calcitriol with cisplatin and docetaxel in advanced NSCLC. Its primary objective was to determine the maximum tolerated dose of calcitriol before the specified chemotherapy regimen. The record also describes a Phase II response objective and provides adverse-event counts. These are descriptions of the trial's aims and recorded information, not a complete report of its findings.
The primary endpoint result is not reported in the registry record. The selected MTD, dose-specific toxicity findings, and criteria supporting dose selection are not reported. The Phase II response result is also not reported. Therefore, the record does not establish what response occurred or how precisely it was estimated. It cannot support a conclusion about the size of a treatment effect, and it cannot establish that any observed response was attributable to calcitriol or to the treatment combination.
The safety entries show affected-participant counts and selected serious adverse-event terms for the registered group. They do not identify a causal relationship to treatment or provide a comparison with another regimen. The population fields also require care: overall enrollment is listed as 34, whereas the primary outcome description refers to eighteen enrolled and sixteen evaluable for toxicity. The registry does not explain how these figures relate.
Because the design is single-group and non-randomized, no randomized comparison against chemotherapy alone or another regimen is available in the record. General statistical interpretation: outcomes observed in a single group can be described, but they cannot by themselves distinguish a treatment effect from other explanations. The study's termination status does not explain why the trial ended, and should not be interpreted as evidence for or against efficacy or safety. The principal conclusion is that the registry documents trial objectives, design, and selected safety information, while the results needed to answer its dose-finding and response questions are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial illustrates the difference between a study objective and a result. The primary objective names a maximum tolerated dose question, but the registry entry does not report the dose identified or the supporting dose-specific toxicity data. Without those elements, readers cannot assess how the dose decision was reached, how much information supported it, or how precisely it was estimated.
It also illustrates why design labels matter. A non-randomized, single-group study can record tolerability and describe outcomes among participants receiving a treatment combination. It cannot provide a randomized estimate of how those outcomes differ from what would have occurred under a comparator. The Phase II response objective therefore needs to be interpreted separately from a comparative efficacy question, especially because response results are not reported in the registry record.
The enrollment and evaluability figures show why analysis populations must be explicit. The record lists 34 participants overall, but the primary outcome description refers to eighteen enrolled and sixteen evaluable for toxicity. It gives a reason for two participants not being evaluable, but does not reconcile these figures or describe how the participants were handled across outcomes. Clear population definitions are necessary for understanding which participants contribute to each estimate.
Finally, the planning assumptions described in the record are not a substitute for the trial's design rationale. Their two-arm equal-allocation framework does not match the registered single-group design. Distinguishing an illustrative sample-size calculation from observed evidence helps prevent planning outputs from being mistaken for trial results, observed power, or a causal treatment comparison.
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 does not report the primary MTD result, the dose levels evaluated, the toxicity criteria, or the dose-selection method. These omissions prevent an independent statistical appraisal of the Phase I dose-finding question. The record also does not provide the Phase II response estimate or its definition, so the response objective cannot be evaluated from the posted information.
The overall enrollment figure is 34, whereas the primary outcome description reports eighteen enrolled and sixteen evaluable for toxicity. The relationship between those numbers is not explained. The reason given for two non-evaluable patients is progression before completing cycle one, but their handling in other analyses is not reported. This makes it difficult to identify the analysis population represented by each outcome entry.
The study has no randomized comparator and is unmasked. It therefore cannot support a randomized between-group contrast, and the record does not describe methods to address potential influences on outcome assessment. Serious and other adverse-event counts are presented for the study group, but attribution, timing, severity grading, exposure duration, and handling of recurrent events are not reported. The adverse-event record also does not provide deaths.
The registry lists zero analysis records and does not report the statistical analysis plan, multiplicity procedures, missing-data methods, or sample-size justification for the trial. The stated planning illustration uses a two-arm framework, unlike the registered single-group design, and its assumptions should not be read as the trial's protocol. The reason for termination is not reported in the registry record. Together, these gaps limit assessment of the trial's conduct, precision, and outcome interpretation; they do not establish that an unreported result was favorable or unfavorable.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase I/II Calcitriol in Lung Cancer — NCT00794547.
- Registry record last updated 2017-12-12; status last verified 2017-11.
- Results first posted 2014-05-05.
- 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
NCT00794547 is a Phase I/II, non-randomized, unmasked, single-group trial sponsored by the University of Michigan Rogel Cancer Center. It studied intravenous calcitriol with cisplatin and docetaxel in advanced non-small cell lung cancer. The primary objective was to determine the maximum tolerated calcitriol dose before cisplatin 75mg/m2 and docetaxel 75 mg/m2 every 3 weeks. The Phase II description concerns response with a fixed calcitriol dose determined in Phase I.
The registry lists enrollment of 34, a start date of 2008-12, primary completion in 2011-10, and terminated status. The primary outcome description reports eighteen patients enrolled and sixteen evaluable for toxicity; two were not evaluable because of progression before completing cycle one. The MTD result, Phase II response results, reason for termination, and detailed statistical methods are not reported in the registry record. Safety fields report 20 of 34 participants affected by serious adverse events and 34 of 34 affected by other adverse events.