CC-4047 With Gemcitabine for Untreated Advanced Carcinoma of the Pancreas: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CC-4047 With Gemcitabine for Untreated Advanced Carcinoma of the Pancreas (NCT00540579), a na phase 1, phase 2 study. The primary outcome is Determination of Maximum Tolerated Dose (MTD), The Dose of Study Drug(s) Which Causes <33% of Patients Treated to Experience Unacceptable Side Effects.

2. Clinical Question

3. Trial Design

This was a phase I/II, completed, single-group study of pomalidomide with gemcitabine in untreated advanced carcinoma of the pancreas. The registry records enrollment of 23 participants. It lists no allocation, no masking, and a single group, so the design does not include a randomized or masked control group. The record describes a dose-escalation approach for pomalidomide rather than a like-for-like comparison of treatment arms.

Gemcitabine was administered at 1000 mg/m2 intravenously on days 1, 8, and 15 of a 28 day cycle. Pomalidomide was administered orally on days 1–21, with daily doses escalated from 2 mg to 10 mg. The study's stated purpose was to determine the appropriate dose and regimen of pomalidomide in combination with gemcitabine. The registry gives a primary-outcome timeframe of 6 months.

The study began in 2007-11, had primary completion in 2008-12, and is recorded as completed. These dates describe the trial record, not the timing of a reported maximum tolerated dose result. Although the record identifies two outcome measures, it lists no analyses. The numerical primary-outcome result, the detailed dose-escalation decisions, and the planned statistical analysis are not reported in the registry record.

Because all participants were treated in one group, the study can describe the experience with the combination and the dose levels used. It cannot estimate a randomized treatment contrast against gemcitabine alone or another control. Differences between people or dose levels should not be interpreted as controlled evidence of comparative treatment effects.

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

Analysis population for the primary outcome, as defined in the registry: Two patients withdrew consent and were unevaluable for DLT. One patient suffered subdural hematoma (non-treatment related) and was unevaluable for DLT.

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.

6. Primary Endpoint

The registry lists the primary outcome as Determination of Maximum Tolerated Dose (MTD), The Dose of Study Drug(s) Which Causes <33% of Patients Treated to Experience Unacceptable Side Effects, measured over 6 months.

The primary endpoint was determination of the maximum tolerated dose, described in the outcome title as the dose of study drug or drugs that causes <33% of treated patients to experience unacceptable side effects. Its unit is milligrams, and its stated timeframe is 6 months. This endpoint is suited to an early-phase dose-finding question: it focuses on tolerability while selecting a dose and regimen for further study, rather than measuring a comparative effect on tumor outcomes.

The registry defines unacceptable side effects, or dose-limiting toxicities, using several criteria. They include inability to complete cycle 1 because of drug-related toxicity; drug-related non-hematological toxicity above Grade 3 despite optimal supportive care, excluding alopecia; febrile neutropenia with ANC <1,000/μL and fever >101° F (38.5° C); and Grade 4 neutropenia before day 21. The definition also excludes a specified instance of Grade 4 neutropenia after day 21 if it resolves within 7 days of the scheduled cycle 2. Other listed criteria concern platelet count <25,000/μL and inability to start cycle 2, day 1 within 7 days of its scheduled start because of drug-related toxicity.

The endpoint definition identifies the toxicity rules but does not establish which dose met the criterion. A numerical maximum tolerated dose result, the number of dose-limiting toxicities at each dose, and the decision process used to select a dose are not reported in the registry record. The registry also notes participants who were unevaluable for dose-limiting toxicity, so the enrolled group should not automatically be treated as the endpoint-evaluable population.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Early-phase dose finding asks a different statistical question from a conventional controlled efficacy comparison. Here, the stated objective was to find an appropriate pomalidomide dose and regimen alongside gemcitabine, and the primary outcome concerned the maximum tolerated dose. The endpoint is tied to dose-limiting toxicity rather than a comparison of outcomes between randomized groups. The registry gives the operational toxicity criteria but does not report the dose-selection method or a numerical maximum tolerated dose.

What does a single-group design allow?

A single-group design can describe outcomes among participants who received the study regimen and can record tolerability at the doses used. It does not create a concurrent control experience. Without randomized allocation to a comparison group, differences from other populations or studies may reflect differences in participants, care, or methods rather than a treatment effect. Thus, adverse-event counts from this study are descriptive and do not provide a comparative risk estimate.

In a dose-escalation study, the observed toxicity experience may inform which dose is considered for later use. The interpretation depends on how participants were assigned to dose levels, how toxicity windows were defined and monitored, and what decision rules governed escalation or stopping. Those operational details, beyond the dose schedule and toxicity criteria, are not reported in the registry record. It would be inappropriate to infer an escalation algorithm from the dose range alone.

How should the toxicity threshold be understood?

The endpoint title frames the maximum tolerated dose using a proportion threshold: the selected dose is described as one at which <33% of treated patients experience unacceptable side effects. In general, a threshold is a decision rule, not itself an observed result. To evaluate whether a dose satisfies it, readers need the number treated at each dose, the number who were evaluable, and the number meeting the dose-limiting toxicity definition. Those dose-specific results are not reported in the registry record.

The toxicity definition is a composite of clinical and laboratory events. A participant could meet the definition through different listed circumstances, such as inability to complete cycle 1 because of drug-related toxicity or a specified severe toxicity. In general, composite definitions make a primary endpoint operational and reproducible, but the interpretation depends on consistent event assessment and attribution. The registry states that the events were drug-related where specified; it does not provide adjudication details or an account of how borderline cases were handled.

What do precision and uncertainty mean?

In general, a confidence interval describes a range of values compatible with the data under a specified statistical model and provides information about estimation precision. A narrower interval indicates more precision than a wider one, while the interval does not remove limitations caused by design or measurement. No confidence interval or other uncertainty estimate for the primary endpoint is reported in the registry record. The adverse-event record also does not include confidence intervals.

In general, binomial methods can describe uncertainty around the proportion of participants experiencing an event. Their usefulness depends on having the relevant numerator and denominator for the outcome and group being assessed. The record includes group-level affected counts and selected event-term percentages, but it does not present dose-specific denominators for dose-limiting toxicity. A dose-level toxicity proportion therefore cannot be reconstructed from the registry information.

What does the analysis record say?

The registry lists two outcome measures and no analyses. This does not establish that no analysis was conducted; it means analysis results are not reported in the registry record. No statistical model, estimator, confidence-interval method, dose-response model, or analysis population definition is stated in the record. The primary endpoint has a 6 months timeframe, but the record does not give a more detailed analysis window or explain how observations after withdrawal were handled.

In general, over-dispersion matters when variability in count data exceeds what a chosen model expects. A model that ignores extra variability may produce uncertainty estimates that are too small. This is a general consideration for count outcomes, not a claim about an analysis performed in this trial: the registry does not describe a count model or any adjustment for over-dispersion. The primary endpoint is presented as a dose in milligrams, and a result estimate is absent.

How should planning illustrations be read?

Sample-size calculations depend on assumptions about the outcome, target effect, significance level, allocation, and statistical model. The registry does not report the trial's own sample-size justification or statistical plan. The planning illustrations associated with the posted results are explicitly distinct from the trial's design and should not be interpreted as the study's prespecified enrollment target or as observed power. In general, observed power is not a substitute for an effect estimate and its uncertainty.

The assumptions used for an illustration do not create missing clinical results. Without a reported primary endpoint estimate, dose-level toxicity counts, and uncertainty measure, readers cannot use a planning calculation to infer which dose was tolerated or how precise the study's conclusion was. The methods record is therefore most informative about the endpoint's intended meaning and the information gaps that remain, rather than about the statistical evidence for a selected dose.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and no analyses. It does not identify a prespecified hierarchy, adjustment for multiple testing, or a strategy for interpreting several outcomes together; these details are not reported in the registry record. The primary outcome is identified, but the numerical result for that outcome is absent. The record also does not state whether any secondary outcome was analyzed or how multiplicity was considered.

Missing data are relevant to the primary endpoint because the registry notes that two participants withdrew consent and were unevaluable for dose-limiting toxicity. One additional participant had a subdural hematoma described as non-treatment related and was also unevaluable. The record does not state how unevaluable participants were handled in the endpoint analysis, whether replacement participants were enrolled, or how missing toxicity assessments were treated. No imputation method or sensitivity analysis is reported.

The enrolled population and the endpoint-evaluable population are not interchangeable. The record reports enrollment of 23 and identifies participants who were unevaluable, but it does not provide dose-specific evaluable denominators or a complete analysis population definition. A denominator for the maximum tolerated dose calculation should not be inferred from enrollment alone.

In general, multiplicity concerns arise when several outcomes, analyses, or comparisons can influence interpretation; missing-data methods address how incomplete observations affect estimates. These are general statistical considerations, not procedures known to have been used in this study. The registry record does not report the protocol's analysis plan, multiplicity handling, or missing-data approach.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thrombosis/thrombus/embolism (17.4%), constipation (4.3%), hyperglycemia (4.3%), ards (4.3%), perforation, gi (4.3%).

The registry reports serious adverse events for the pomalidomide/gemcitabine group, with 23 participants at risk and 13 affected. For other adverse events, 23 were at risk and 23 were affected. These are participant counts in the registry record; they are not a comparison between treatment groups, because the study had a single group.

The serious adverse-event terms with reported percentages are thrombosis/thrombus/embolism at 17.4%, and constipation, hyperglycemia, ARDS, perforation, GI, and GI - Other at 4.3% each. These percentages describe the listed terms as recorded. The record does not explain whether participants could contribute to more than one term, so the percentages should not be added or interpreted as mutually exclusive categories. It also does not provide severity detail beyond the serious-event classification for each listed term.

The registry's deaths field does not contain a reported count. This should be read as deaths not reported in the registry record, rather than as evidence that no deaths occurred. In general, adverse-event counts describe observed events in the recorded group; without a comparator, exposure-adjusted rates, and fuller event details, they do not establish that the treatment caused an event or allow a comparative safety conclusion.

12. What the Result Does, and Does Not, Mean

The record establishes that a phase I/II, single-group study evaluated pomalidomide with gemcitabine in untreated advanced carcinoma of the pancreas. It gives the dosing schedule, the intended dose-finding purpose, the primary endpoint definition, and criteria for dose-limiting toxicities. It also records adverse-event counts and selected serious adverse-event terms. These details describe what was studied and how the primary tolerability question was framed.

The record does not report the numerical maximum tolerated dose, dose-specific toxicity results, or an analysis estimate with uncertainty. It therefore does not allow readers to determine from the posted results which dose met the stated threshold. The absence of a reported result is not evidence that no dose was selected or that no analysis occurred; those outcomes are simply not reported in the registry record.

The single-group design also sets limits on what the data can establish. There is no randomized control comparison, so the record cannot estimate a comparative effect of the combination versus gemcitabine alone or another regimen. The adverse-event figures summarize participants in the treated group but do not by themselves establish causation. Nor do they provide a complete account of event timing, duration, recurrence, or dose-specific patterns.

In general, a well-defined endpoint helps readers understand which observations count toward a study question. It does not replace the endpoint result, analysis population, or uncertainty estimate. Here the toxicity criteria are detailed, but key information needed to assess the primary outcome is missing from the registry record. Similarly, the enrolled total does not by itself show how many participants contributed evaluable toxicity observations at each dose.

The study is best understood as an early-phase, dose-finding investigation with an identifiable safety-focused objective and limited comparative capacity. The registry record supports a description of the design and some reported safety information. It does not support a numerical conclusion about the maximum tolerated dose or a controlled conclusion about treatment benefit or harm.

13. Why This Trial Matters Statistically

This study illustrates why early-phase dose-finding results require more than a stated dose range and a toxicity definition. A decision about maximum tolerated dose depends on the pattern of dose-limiting toxicities at the doses studied, the numbers evaluated at each dose, and the rules used to make dose decisions. The registry gives the endpoint criterion and toxicity definitions, but not the dose-specific results or the selected dose. That gap makes the primary question impossible to assess from the registry record alone.

The design also illustrates the distinction between studying a regimen and estimating a comparative effect. A single group can generate descriptive information about participants exposed to the combination, while a randomized comparator is needed for a direct treatment contrast. The adverse-event counts are useful as a description of what the record reports, but they are not evidence from a controlled comparison.

From a statistical reporting perspective, analysis populations and missing observations matter in dose-finding work. The registry identifies participants who were unevaluable for dose-limiting toxicity, yet does not state how those participants were handled or give dose-level denominators. Without those details, an overall enrollment figure cannot substitute for the denominator used to evaluate tolerability.

Finally, the record shows the value of distinguishing an endpoint definition from an endpoint result. A precise definition can make a clinical question understandable, but readers also need the observed outcome and its uncertainty to judge what the study found. Here, the endpoint's statistical interpretation remains constrained because the numerical maximum tolerated dose result and analyses are not reported 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 main trial-specific limitation is that the registry record does not report the primary endpoint result. Although the study aimed to determine a maximum tolerated dose and lists a threshold and detailed dose-limiting toxicity criteria, it provides no numerical dose selected, no toxicity counts by dose, and no estimate of uncertainty. The core dose-finding conclusion therefore cannot be evaluated from the posted results.

The analysis population is also unclear. The record identifies two participants who withdrew consent and one with a non-treatment-related subdural hematoma as unevaluable for dose-limiting toxicity, but it does not explain how those participants were treated analytically. It does not give dose-specific numbers at risk or evaluable. This prevents independent assessment of the denominator underlying any dose-specific tolerability proportion.

The study has no control group, allocation, or masking recorded. Consequently, the results cannot provide a randomized comparison, and adverse-event summaries cannot isolate effects attributable to the combination. The registry also gives no participant characteristics, detailed eligibility criteria, or fuller event descriptions in the information available for this trial.

Other statistical details are not reported in the registry record, including the analysis plan, sample-size justification, missing-data method, multiplicity approach, and method for selecting a dose. The adverse-event record gives selected terms and percentages but does not clarify overlap between terms or report deaths. These gaps limit the depth and precision of interpretation even though the study's treatment schedule and toxicity definitions are described.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: CC-4047 With Gemcitabine for Untreated Advanced Carcinoma of the Pancreas — NCT00540579.
• Registry record last updated 2013-03-13; status last verified 2013-02.
• Results first posted 2013-03-13.
• 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.

18. Record Summary

NCT00540579 is a completed phase I/II, single-group study of pomalidomide with gemcitabine for untreated advanced carcinoma of the pancreas. The registry records enrollment of 23 participants and describes escalating daily pomalidomide doses from 2 mg to 10 mg alongside a gemcitabine schedule. Its primary outcome was maximum tolerated dose, with defined dose-limiting toxicity criteria and a 6 months timeframe.

The registry reports 13 participants affected by serious adverse events and 23 affected by other adverse events. It does not report a numerical maximum tolerated dose result or analysis results. Two participants who withdrew consent and one with a non-treatment-related subdural hematoma were unevaluable for dose-limiting toxicity. The study has no randomized comparator, and the registry record does not report the statistical plan, analysis populations, or missing-data methods.