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 Capecitabine and Celecoxib in Patients With Solid Cancers That Have Been Previously Treated With Standard Therapies (NCT01705106), a na phase 1 study. The primary outcome is AUC of Celecoxib on Combination Therapy (Day 14) and AUC of Celecoxib on Celecoxib Monotherapy(Day 7).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01705106 |
| Phase | Phase 1 |
| Condition | Unspecified Adult Solid Tumor, Protocol Specific |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 21 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Chicago |
| Results posted | Yes |
2. Clinical Question
Population
People with advanced solid malignancies, including tumors described as metastatic or not removable by surgery, who had previously received standard therapies. The registry condition is listed as Unspecified Adult Solid Tumor, Protocol Specific.
Intervention
The planned treatment combined oral capecitabine and oral celecoxib. Celecoxib began before capecitabine and continued during combination treatment.
Comparator
The primary pharmacokinetic question compares celecoxib exposure during combination therapy with celecoxib exposure during celecoxib monotherapy. This is a planned comparison of treatment conditions, not a randomized comparison between separate trial arms.
Primary question
Does celecoxib exposure, measured by its area under the concentration-time curve (AUC), differ between combination therapy and celecoxib monotherapy? The registry planned to estimate the mean ratio of those AUCs and a 90% confidence interval. No participants were analyzed for this primary endpoint, and the data were not collected.
The clinical rationale in the registry is that capecitabine is a chemotherapy drug intended to affect tumor-cell growth, while celecoxib may affect enzymes involved in cell growth. The study was designed as a drug-drug interaction investigation: its central question was about celecoxib pharmacokinetics when capecitabine was added, rather than a direct test of treatment benefit against a control group. The registry also lists response rate, drug-related toxicities, CYP2C9 genotype, and a pharmacokinetic interaction model as secondary outcomes. The record does not report results for those questions in the primary endpoint description.
3. Trial Design
This was a phase 1, single-group study sponsored by the University of Chicago. The registry lists allocation as not applicable and masking as none. Enrollment was 21. The study began on 2012-08-29, had a primary completion date of 2016-02-10, and is recorded as terminated. The reason given for early termination was slow accrual.
The treatment description specifies celecoxib by mouth twice daily for 7 days in course 0, then on days 1-21 of course 1 and subsequent courses. Capecitabine by mouth twice daily was to be given on days 1-14 beginning in course 1. Courses were to repeat every 21 days in the absence of disease progression or unacceptable toxicity. Those planned treatment details describe the regimen; they do not establish how long any participant actually received it.
The primary endpoint description sets out a comparison between celecoxib AUC on day 14 of combination therapy and celecoxib AUC on day 7 of celecoxib monotherapy. That makes the intended pharmacokinetic comparison one between treatment conditions, not between randomized groups. The registry does not report a randomized control arm, and the study design is not a like-for-like comparison of separate treatment arms.
Although enrollment is recorded, the primary endpoint population statement says the trial ended early because of slow accrual, none of the participants was analyzed, and data were not collected. The registry therefore documents the intended design and regimen but not a completed primary pharmacokinetic evaluation. The extent to which the planned treatment schedule was followed is not reported in the registry record.
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 | Treatment (Capecitabine, Celecoxib) |
|---|---|
| STARTED | 21 |
| COMPLETED | 21 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: The study was terminated early due to slow accrual, thus none of participants was analyzed. Data were not collected.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Treatment (Capecitabine, Celecoxib) |
|---|---|---|
| Participants analysed | 21 | |
| Age, Continuous | years | 57.5 (52 to 67) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 16 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 19 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as AUC of Celecoxib on Combination Therapy (Day 14) and AUC of Celecoxib on Celecoxib Monotherapy(Day 7), measured over Day 7 and 14 post treatment.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint concerns celecoxib exposure under two treatment conditions. Exposure is measured with the area under the concentration-time curve, or AUC, which represents the area beneath a drug concentration profile over the specified measurement period. In general, AUC is used in pharmacokinetic studies to characterize how much drug exposure occurs over time. It is not itself a measure of tumor response or a direct measure of clinical benefit.
The registry planned to estimate AUC for each subject under each condition: celecoxib monotherapy on day 7 and combination therapy with capecitabine on day 14. It then planned to estimate the mean ratio of the combination-therapy AUC to the monotherapy AUC, together with a 90% confidence interval. A ratio expresses one exposure relative to the other; the interval would describe uncertainty around the estimated mean ratio. This kind of comparison is relevant to a drug-drug interaction question because adding another drug could change the measured exposure of the drug being studied.
These are planned measurements and analyses, not observed findings. The registry states that no participants were analyzed for this endpoint and that data were not collected. It consequently reports no AUC values, mean ratio, or confidence interval. The amount or direction of any pharmacokinetic difference cannot be determined from this endpoint record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record supports a description of the study’s intended question and its early termination, but it does not support an estimate of the primary pharmacokinetic effect. The study planned to compare celecoxib AUC during combination treatment with celecoxib AUC during monotherapy. However, the primary endpoint statement explicitly says that none of the participants was analyzed and that data were not collected. There is therefore no posted mean ratio or 90% confidence interval to interpret.
This absence matters because a study question and a study finding are not the same thing. The endpoint definition specifies what investigators intended to measure and how they intended to summarize it. It does not demonstrate that celecoxib exposure changed, remained similar, or was estimated with any particular degree of precision. No direction or magnitude of a primary pharmacokinetic effect is reported in the registry record.
The recorded enrollment of 21 does not change that conclusion. Enrollment indicates that participants entered the study, but the primary endpoint population statement says none was analyzed for the endpoint. A reader should not treat enrollment as the analyzed sample size or assume that all enrolled participants contributed usable pharmacokinetic observations. The reasons for participant-level non-analysis beyond the reported early termination and slow accrual are not reported in the registry record.
The record also contains safety figures for the treatment group. Those figures are a distinct part of the posted information and do not supply the missing AUC measurements. The registry lists 21 at risk for serious adverse events, with 9 affected, and 21 at risk for other adverse events, with 20 affected. It also lists serious-event terms with percentages. These safety data should be read as registry-reported counts and percentages, not as evidence about the primary pharmacokinetic comparison. Deaths are not reported in the registry record.
Likewise, the listed secondary outcomes do not establish that their analyses were completed. The registry lists CYP2C9 genotype, response rate, drug-related toxicities, and a pharmacokinetic interaction model. It records no analyses. Results for those secondary questions are not reported in the registry record. The presence of an outcome name indicates that it was part of the registered study record, not that a result is available.
Because the trial was single-group and had no randomized control arm, the planned within-study pharmacokinetic comparison should not be recast as a treatment-versus-control efficacy comparison. The registry’s stated focus is a drug-drug interaction, and the available primary endpoint information is descriptive of the plan rather than an estimate. The most precise conclusion is that the registered primary comparison was not evaluated in the reported record.
9. Statistical Methods Explained
The central statistical idea in the planned primary analysis is to compare a subject’s celecoxib exposure under two treatment conditions. AUC is a pharmacokinetic summary: conceptually, it captures concentration accumulated over time across a defined measurement period. In general, AUC is useful when the question concerns exposure, because a single concentration measurement may not represent the full concentration profile. The registry identifies day 7 for celecoxib monotherapy and day 14 for combination therapy as the measurement occasions.
The primary description says that AUC parameters would be estimated for each subject under each treatment condition. It then specifies a mean ratio, with combination therapy in the numerator and celecoxib monotherapy in the denominator. In general, ratios make a relative comparison possible when the scientific question concerns proportional exposure rather than an absolute difference. The ratio’s interpretation depends on the reported estimate and its uncertainty; neither is available in this record. No ratio can be inferred solely from the endpoint description.
A confidence interval is, in general, a range of values compatible with the data and the statistical procedure used, expressing uncertainty in an estimate. The registered plan calls for a 90% confidence interval around the mean ratio. That is a planned confidence level, not a reported interval. Since no participants were analyzed for the primary endpoint and no data were collected, there is no interval in the record from which to judge precision. A planned confidence interval cannot be treated as evidence that an estimate was precise.
The intended measurements are linked to pharmacokinetic sampling, but the registry does not report details such as sampling times, assay procedures, the approach to concentrations below quantification, or the specific method used to estimate AUC. Those details are not reported in the registry record. It would therefore be inappropriate to infer the exact calculation method, the shape of a concentration profile, or any assumptions about its distribution.
The comparison is not a randomized two-arm contrast. The study is listed as single group, with allocation not applicable and no masking. The primary endpoint describes two treatment conditions for each subject. In general, measurements made under more than one condition in the same person can account for some stable between-person variation, because each person contributes observations to both conditions. But the registry’s endpoint statement does not provide enough detail to characterize the analysis as a particular paired model, to determine how repeated observations would have been handled, or to establish whether all subjects would have completed both conditions.
The record also lists a pharmacokinetic interaction model as a secondary outcome. In general, such a model can represent how exposure under a combination condition relates to exposure under a single-drug condition. The registry does not specify the model form, covariates, estimation procedure, or decision criteria. Those details are not reported in the registry record. The model’s name alone does not establish what parameters would be estimated or what findings it produced.
CYP2C9 genotype is another listed secondary outcome. In general, genotype analyses may explore whether inherited variation is associated with drug handling or other measured outcomes. The registry does not report the planned genotype categories, the statistical test, or any genotype results. It also lists response rate and drug-related toxicities, but does not describe the criteria used to define response, the toxicity grading procedure, or the methods for analyzing those outcomes. Those analytic details are not reported in the registry record.
The registry reports five outcome measures and no analyses. That distinction is important: having outcome measures listed is not equivalent to having estimates, hypothesis tests, or model results. The statistical analysis plan beyond the stated mean ratio and 90% confidence interval is not reported in the registry record. In particular, the record does not specify hypothesis tests, covariate adjustment, handling of repeated measurements, or an interim analysis plan.
For general statistical context, over-dispersion occurs when observed variability is greater than a model’s assumed variability. It can make standard errors too small and confidence intervals too narrow if it is not accounted for. This concept is relevant to count outcomes such as adverse events, but the registry record does not report a model for those data or identify over-dispersion as an issue. It should not be read as a finding about this trial.
Sample-size calculations, when displayed as planning illustrations, answer a hypothetical design question: how many participants might be needed under stated assumptions and for a specified target effect. They are not observed power and do not replace an analysis of collected outcomes. The registry does not report a sample-size justification for the study, and the primary endpoint data were not collected. Any planning illustration should therefore be kept separate from the actual enrollment and from the unavailable primary effect estimate.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several outcomes: a primary celecoxib AUC comparison and secondary measures covering CYP2C9 genotype, response rate, drug-related toxicities, and a pharmacokinetic interaction model. It records no analyses. Consequently, the record does not establish which outcomes were tested, whether any were designated as confirmatory beyond the primary endpoint, or how results across outcomes would have been interpreted.
Multiplicity arises in general when multiple outcomes, comparisons, time points, or subgroups are examined. Conducting many statistical tests can increase the chance of finding an apparently notable result by chance. Statistical plans may address that issue through a prespecified hierarchy or adjustment procedure, but the registry does not report a multiplicity strategy. No adjustment should be assumed, and no multiplicity-adjusted result is available to interpret.
The primary endpoint description gives a mean ratio and a 90% confidence interval as the planned summary. It does not say whether the interval was intended as a formal hypothesis test or how it would relate to any other outcome analyses. The inferential plan beyond that description is not reported in the registry record.
The primary endpoint statement says that none of the participants was analyzed and that data were not collected. Thus, there are no primary endpoint observations in the record to classify as missing, excluded, or censored. The record does not describe a missing-data method, an analysis population definition, or a sensitivity analysis. These details are not reported in the registry record. It would be inaccurate to infer that missing observations were imputed, that an intention-to-treat analysis was conducted, or that a per-protocol population was analyzed.
Enrollment and analysis are distinct quantities in this study record. Enrollment is 21, while the primary endpoint population statement says none of the participants was analyzed. That statement should guide interpretation of the primary outcome even though the registry separately contains safety counts. The safety figures do not establish that a primary pharmacokinetic analysis took place.
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 |
|---|---|---|---|
| Treatment (Capecitabine, Celecoxib) | 9 | 21 | 42.9% |
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 |
|---|---|
| Treatment (Capecitabine, Celecoxib) | 20 of 21 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment (Capecitabine, Celecoxib) |
|---|---|---|
| Diarrhea | Gastrointestinal disorders | 2 of 21 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 2 of 21 |
| Respiratory, thoracic and mediastinal disorders - Other (Pneumonia) | Respiratory, thoracic and mediastinal disorders | 2 of 21 |
| Small intestinal obstruction | Gastrointestinal disorders | 2 of 21 |
| Musculoskeletal and connective tissue disorder - Other, specify | Musculoskeletal and connective tissue disorders | 1 of 21 |
| Chest pain | Cardiac disorders | 1 of 21 |
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | 1 of 21 |
| Seizure | Nervous system disorders | 1 of 21 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Capecitabine, Celecoxib) |
|---|---|---|
| Fatigue | General disorders | 12 of 21 |
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | 12 of 21 |
| Diarrhea | Gastrointestinal disorders | 11 of 21 |
| Anorexia | Metabolism and nutrition disorders | 9 of 21 |
| Nausea | Gastrointestinal disorders | 8 of 21 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 7 of 21 |
| Abdominal Pain | Gastrointestinal disorders | 5 of 21 |
| Mucositis | Gastrointestinal disorders | 4 of 21 |
| Peripheral sensory neuropathy | Nervous system disorders | 4 of 21 |
| Vomiting | Gastrointestinal disorders | 4 of 21 |
Serious events with the highest arm-level rate: diarrhea (9.5%), dyspnea (9.5%), respiratory, thoracic and mediastinal disorders - other (pneumonia) (9.5%), small intestinal obstruction (9.5%), musculoskeletal and connective tissue disorder - other, specify (4.8%).
The registry reports 21 participants at risk for serious adverse events and 9 affected. For other adverse events, it reports 21 at risk and 20 affected. These are registry counts for the treatment group. The record also lists serious-event terms with percentages: Diarrhea, 9.5%; Dyspnea, 9.5%; Respiratory, thoracic and mediastinal disorders - Other (Pneumonia), 9.5%; Small intestinal obstruction, 9.5%; Musculoskeletal and connective tissue disorder - Other, specify, 4.8%; and Chest pain, 4.8%.
The listed terms and percentages describe what the registry reports; they do not provide a full account of event timing, duration, severity beyond the serious-event classification, or relationship to treatment. The registry record does not report deaths. It also does not provide detail in the listed figures about whether an individual experienced more than one event, so the terms should not be added or treated as mutually exclusive categories.
These safety figures are separate from the primary pharmacokinetic endpoint. The statement that no participants were analyzed and data were not collected applies to the primary endpoint; it does not erase the distinct safety information included in the registry. Conversely, safety counts cannot be used to infer AUC values or a drug interaction result.
12. What the Result Does, and Does Not, Mean
The registered study asked whether celecoxib exposure differed when capecitabine was added, comparing AUC on day 14 of combination therapy with AUC on day 7 of celecoxib monotherapy. Its proposed summary was a mean ratio with a 90% confidence interval. The registry record does not contain the estimated ratio or interval, because it states that the study was terminated early due to slow accrual, none of the participants was analyzed for the primary endpoint, and data were not collected.
That means the available primary endpoint information cannot establish the presence, direction, size, or precision of a pharmacokinetic difference. It also cannot establish that exposure was unchanged: absence of an estimate is not evidence of equivalence. A confidence interval would be needed to assess the range of effects compatible with the data, but no such interval is reported.
The study’s design also constrains what could be concluded. It was a single-group study without a randomized control arm. Its registered primary question concerned pharmacokinetics across treatment conditions rather than a comparison of clinical outcomes between treatment groups. The registry does not provide a basis for attributing a clinical response to the combination or for comparing it with another regimen.
The record lists adverse-event counts and terms, but these address safety reporting rather than the missing AUC comparison. They should be interpreted as the posted safety figures, with the limitations of the detail available in the registry. The record does not report deaths, and it does not give the information needed to infer causation from the event listings.
Finally, the planned secondary outcomes do not substitute for results. Although genotype, response rate, drug-related toxicities, and a pharmacokinetic interaction model are listed, the record reports no analyses. The most defensible reading is therefore limited: this registry describes the study question, treatment schedule, early termination, and safety figures, but it does not provide a primary pharmacokinetic result or reported analyses of the listed secondary outcomes.
13. Why This Trial Matters Statistically
This trial illustrates a basic distinction in clinical research between a well-defined question and an answer supported by analyzed data. The registry describes a specific pharmacokinetic question: whether celecoxib exposure, measured by AUC, differed between monotherapy and combination treatment. It also identifies the planned relative summary and confidence interval. Yet the record states that the primary endpoint data were not collected and no participants were analyzed. A precise endpoint definition cannot by itself produce an effect estimate.
The distinction between enrollment and analysis is also important. The registry records enrollment of 21, but the primary endpoint population statement says none was analyzed. Readers should not treat the enrolled number as the primary endpoint sample size or assume that an estimate exists. This is particularly relevant when a study stops early: the information in the record may include trial progress and some safety data while leaving the main scientific question unanswered.
The design provides another statistical lesson. A single-group study can be organized to compare pharmacokinetic conditions, but it is not the same as a randomized comparison of separate groups. The registered question is about drug exposure under two conditions, not a controlled estimate of clinical efficacy. Interpreting it within that scope avoids drawing conclusions the design was not intended to support.
Finally, the record distinguishes listed outcomes from completed analyses. Multiple endpoints appear in the registration, but the record reports no analyses. Statistical interpretation depends on estimates, uncertainty, and methods—not merely on a list of planned measures. Here, the main statistical takeaway is the limit of the evidence available: the intended primary comparison is described, but its result is not reported.
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 central limitation is that the planned primary endpoint was not analyzed and its data were not collected, according to the registry. Therefore, the record offers no AUC estimates, mean ratio, or confidence interval for the drug-interaction question. The study’s early termination due to slow accrual further limits what can be concluded from its planned design.
Although enrollment is recorded as 21, the primary endpoint statement says none of the participants was analyzed. The registry does not explain participant-level completion of the treatment schedule or provide an analysis population for the primary endpoint. It is not possible to determine from the record whether participants completed both treatment conditions or how many might otherwise have had evaluable pharmacokinetic measurements.
The design is single group, with allocation not applicable and no masking. There is no randomized control arm for a like-for-like treatment comparison. The intended comparison is between celecoxib treatment conditions, and the record does not support conclusions about comparative clinical efficacy.
The registry lists secondary outcomes but records no analyses. Their definitions, analytic methods, and results are not reported in the registry record. The statistical analysis plan beyond the specified primary mean ratio and 90% confidence interval is also not reported. In particular, the record does not describe missing-data procedures, multiplicity handling, model specifications, or interim analyses.
Safety information is present, but the listed figures do not describe event timing, duration, or treatment relationship. The record does not report deaths. The serious-event terms and percentages should therefore be understood as the extent of safety detail recorded, not a complete account of every aspect of safety or a basis for causal attribution.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Capecitabine and Celecoxib in Patients With Solid Cancers That Have Been Previously Treated With Standard Therapies — NCT01705106.
- Registry record last updated 2018-05-30; status last verified 2018-04.
- Results first posted 2018-05-30.
- 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 phase 1, single-group study of capecitabine and celecoxib in people with advanced solid malignancies previously treated with standard therapies. The planned primary endpoint compared celecoxib AUC during combination therapy and celecoxib monotherapy, with a mean ratio and 90% confidence interval as the intended summary. The study enrolled 21 and was terminated early because of slow accrual. The primary endpoint statement says none of the participants was analyzed and data were not collected.
The record lists CYP2C9 genotype, response rate, drug-related toxicities, and a pharmacokinetic interaction model as secondary outcomes, and records no analyses. It also reports treatment-group safety figures, including 9 affected among 21 at risk for serious adverse events and 20 affected among 21 at risk for other adverse events. Deaths are not reported in the registry record. The principal statistical limitation is the absence of a reported primary pharmacokinetic estimate.