Etoposide, Cyclophosphamide, Thalidomide, Celecoxib, and Fenofibrate in Relapsed or Progressive Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Etoposide, Cyclophosphamide, Thalidomide, Celecoxib, and Fenofibrate in Relapsed or Progressive Cancer (NCT00357500), a na phase 2 study. The primary outcome is Therapy Completion Rate.

2. Clinical Question

The study’s stated rationale is that the chemotherapy drugs may act against cancer cells, while thalidomide, celecoxib, and fenofibrate may affect cancer growth through anti-angiogenic mechanisms; celecoxib is also described as potentially affecting enzymes involved in cell growth. These are the rationale recorded for the trial, not evidence of a treatment effect. The posted record does not report a numerical result for the primary question, so the proportion meeting the endpoint and its precision cannot be assessed from the registry entry.

3. Trial Design

This was a phase II, single-group trial sponsored by Dana-Farber Cancer Institute. The registry lists an enrollment of 101 and a status of completed. The recorded start was 2005-01, and primary completion was 2013-02. The population was described as young patients with relapsed or progressive cancer, across several pediatric and other cancer categories listed in the registry.

Patients were assigned to a five-drug metronomic antiangiogenic regimen: thalidomide, celecoxib, fenofibrate, etoposide, and cyclophosphamide. The official title describes the regimen as oral. The record gives drug-specific dosing information, including dose adjustments by weight for some agents, but does not provide a separate control treatment. Allocation is listed as NA, the model as single-group, and masking as none.

A single-group design can describe outcomes among people who received the regimen, but it does not by itself establish how those outcomes compare with what would have occurred under another treatment or without the regimen. The trial’s design therefore supports a descriptive reading of the posted outcomes rather than a randomized treatment contrast. The record’s listed analysis population is all treated patients; the number treated is not reported separately from the enrollment figure.

The registry lists 27-week progression-free survival, 27-week overall survival, and best response as secondary outcomes. It does not report the detailed statistical plan, the protocol’s eligibility criteria, or a rationale for the enrollment target. Details about interim analyses are 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.

Before assignment: Patients must have recovered or stabalized the toxicity from prior therapy.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis dataset is comprised of all treated patients.

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: The analysis population represents patients who started treatment.

6. Primary Endpoint

The registry lists the primary outcome as Therapy Completion Rate, measured over 27 weeks.

The primary outcome is named “Therapy Completion Rate,” with a unit of proportion of patients and a timeframe of 27 weeks. Its definition is more specific than the name alone: it is the proportion of patients who were alive at 27 weeks, had no progressive disease, and had tolerated therapy. Thus, the endpoint brings together survival status, disease progression, and treatment tolerance in one classification.

Progression was defined using tumor-type-specific criteria. For relevant tumors, assessment could use gadolinium-enhanced MRI and other imaging modalities. The record describes progression for most patients through a specified increase in the product of lesion diameters, new disease, disease-attributable clinical deterioration, or death. For patients with leukemia, progression criteria included an increase in circulating cells, extramedullary disease, or other clinical evidence of progression. The registry does not give the observed number or proportion meeting the primary endpoint.

In general, a combined endpoint can capture several clinically relevant ways a patient may fail to meet a treatment objective, but its components may have different meanings and frequencies. Interpretation should therefore begin with the exact definition rather than the endpoint label. The registry lists a 90% confidence interval as the measure of precision, but the interval and point estimate are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group phase II study and identifies a binary primary outcome: whether each treated patient met the combined 27-week definition. A proportion is a natural summary for an outcome classified as meeting or not meeting a stated criterion. The registry specifies a 90% confidence interval for this outcome, but does not post the proportion or interval. It also does not report the statistical methods used to construct the interval.

General: reading a confidence interval. A confidence interval expresses the uncertainty associated with an estimated quantity under a particular statistical method and its assumptions. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. An interval is not a range that guarantees the true value lies within it, and its interpretation depends on how the data were collected and analyzed. Because the interval is absent from this registry record, the precision of the primary estimate cannot be judged.

The endpoint combines alive status, progression status, and treatment tolerance at 27 weeks. This definition creates a patient-level classification based on multiple conditions. In general, when a participant must satisfy every component to count as meeting a combined endpoint, failure of any component means the overall endpoint is not met. Component-level results can help show which aspects of the outcome are driving the overall summary, but those component results are not reported in the registry record.

The progression definition uses different assessment criteria according to tumor type and location, including imaging and clinical criteria, and separate criteria for leukemia. In general, outcome assessment that depends on different disease-specific rules requires consistent application and clear documentation. The registry describes the criteria but does not report assessor procedures, central review, or how uncertain or unevaluable assessments were handled. Those details are not reported in the registry record.

General: why the design matters. A single-group analysis estimates outcomes in the group that received the regimen. Without a concurrent comparator, it cannot separate the contribution of treatment from other explanations for observed outcomes. Randomization, when used, helps create comparable groups for a treatment contrast; this study is not listed as randomized and has no comparator arm. The posted record consequently supports description, not a controlled estimate of relative effect.

The study is listed as unmasked. In general, lack of masking can affect outcome assessment or decisions about care, particularly when outcomes involve judgment. The primary endpoint includes disease progression and therapy tolerance, so the criteria and assessment process matter. The registry does not report whether independent or blinded outcome review was used, and such procedures should not be assumed.

The registry lists all treated patients as the analysis population. In general, defining the analysis population in advance clarifies who contributes to an estimate and how protocol deviations or treatment discontinuation are handled. The number treated, the number included in each endpoint analysis, and the handling of patients without a 27-week assessment are not reported in the registry record. The enrollment figure alone does not resolve those questions.

General: missing observations and precision. A missing endpoint assessment is not automatically equivalent to either success or failure. Statistical approaches to missing data make different assumptions, and conclusions can depend on those assumptions. The registry does not report the amount of missing outcome data or the method used to handle it. It is therefore not possible to determine how missingness might have affected the endpoint estimate.

The record names secondary outcomes, but does not report their estimates or the analysis plan. In general, assessing multiple outcomes raises questions about which analyses are primary, whether results are confirmatory or exploratory, and how the risk of chance findings is addressed. The registry does not report a multiplicity strategy or adjustment. It also does not report a sample-size justification, interim analysis plan, or detailed statistical analysis plan. Those methods cannot be inferred from the phase designation or enrollment figure.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("5-drug Metronomic Antiangiogenic Regimen")
n      <- c(97)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  5-drug Metronomic Antiangiogenic Regimen  97  0  0.0  0.0  3.7  0.0  3.8  0.0  3.7

11. Multiplicity, Missing Data and Analysis Populations

The registry names one primary endpoint and three secondary outcomes: 27-week progression-free survival, 27-week overall survival, and best response. It lists four outcome measures in total, but the additional measure and its result are not reported in the registry record. No numerical results for the named outcomes are posted.

Multiplicity concerns arise in general when several outcomes or comparisons are examined. The more analyses that are used to support conclusions, the greater the importance of distinguishing prespecified primary analyses from secondary or exploratory ones. A plan may use a hierarchy, adjust thresholds, or explicitly treat additional outcomes as descriptive. The registry record does not report which approach was used, whether any adjustment was planned, or how conclusions across outcomes were to be interpreted.

The analysis population is described as all treated patients. The record does not report how many enrolled participants were treated, how many had outcome assessments, or how missing endpoint information was handled. It also does not report exclusions, imputation, sensitivity analyses, or a missing-data assumption. These omissions matter because estimates based only on participants with available assessments can be affected if availability is related to disease status, treatment tolerance, or other factors.

No analyses are listed in the registry record. Details of the statistical analysis plan, sample-size justification, and interim analyses are not reported in the registry record. It is therefore not possible to establish from the entry whether analyses followed a prespecified plan or how incomplete observations and multiple outcomes were addressed.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: leukocytes (58.8%), neutrophils (47.4%), lymphopenia (38.1%), hemoglobin (21.6%), fatigue (11.3%).

The registry’s adverse-event information lists 97 participants at risk for serious events and 74 affected. For other events, it lists 97 at risk and 81 affected. These are the posted counts; the registry record does not provide additional detail on the event definitions, observation period, or participant-level overlap between categories. The counts should not be added or treated as independent groups.

The serious adverse-event terms with percentages listed are Leukocytes, 58.8%; Neutrophils, 47.4%; Lymphopenia, 38.1%; Hemoglobin, 21.6%; Fatigue, 11.3%; and Febrile neutropenia, 9.3%. The registry presents these as serious-event terms. It does not give further information in this record about grading, duration, recurrence, or how each percentage was calculated, so those details should not be inferred.

In general, adverse-event summaries describe events recorded during a study; they do not by themselves establish that the study treatment caused an event. Without a concurrent comparator, event frequencies cannot be used as a controlled comparison with another regimen. The adverse-event record has no reported death count. A null death entry means the death figure is not reported in the registry record, not that no deaths occurred.

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

The registry record documents a phase II, single-group study of an oral five-drug regimen in young patients with relapsed or progressive cancer. It defines a primary 27-week outcome that requires patients to be alive, without progressive disease, and to have tolerated therapy. It also identifies secondary outcomes and lists adverse-event information. These design and measurement details describe what the study set out to assess.

The record does not include the primary endpoint estimate or its 90% confidence interval. It also does not post numerical results for progression-free survival, overall survival, or best response. Therefore, the registry entry does not show how many treated patients met the primary endpoint, how variable or precise an estimate was, or what the secondary outcomes were. No conclusion about treatment benefit can be drawn from these missing outcome results.

Even if outcome estimates were available, the single-group design would remain an important constraint. In general, an outcome observed after treatment cannot be attributed to treatment alone without a suitable comparison that addresses other explanations. This trial has no separate comparator group, and masking is listed as none. The registry record does not provide a randomized estimate of the regimen’s effect relative to another approach.

The adverse-event record provides counts and a list of serious-event terms with percentages, but it does not provide a controlled safety comparison. It also does not report the death count. These data should be read as registry safety descriptions rather than evidence that events were or were not caused by the regimen.

Overall, the posted record is informative about the study design, regimen, outcome definitions, and some safety reporting. It is not sufficient to quantify the primary outcome or determine its precision, and it does not support a comparative treatment-effect conclusion.

14. Why This Trial Matters Statistically

This trial is statistically notable for the way its primary endpoint is defined. The label “Therapy Completion Rate” might sound like a measure of treatment completion alone, but the registry definition also requires survival at 27 weeks and no progressive disease, as well as tolerance of therapy. Reading the operational definition is essential to understanding what the endpoint represents.

The study also illustrates the distinction between having a stated outcome and having a posted outcome result. The registry specifies a 90% confidence interval for the primary measure, yet does not report the estimate or interval. Without those quantities, readers cannot evaluate either the observed proportion or its precision. A clear endpoint definition cannot substitute for outcome reporting.

The design provides a further statistical lesson. A single-group phase II study can describe outcomes among treated patients, but it cannot furnish a direct randomized comparison. That limitation is especially relevant when interpreting outcomes in a population with different cancer types and disease-specific progression criteria. The record does not report subgroup results that would allow readers to examine those differences.

Finally, the record identifies multiple secondary outcomes and adverse-event summaries but does not report a detailed analysis plan or multiplicity approach. This matters because interpretation depends not only on what outcomes were named, but also on how they were analyzed and how uncertain or incomplete observations were handled. Those methodological details are not reported in the registry record.

15. 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 limitation for statistical interpretation is that the primary endpoint estimate and its 90% confidence interval are not reported in the registry record. Numerical results for the named secondary outcomes are also absent. The registry entry consequently does not permit assessment of the trial’s observed clinical outcomes or their precision.

The single-group design has no concurrent control arm, and masking is listed as none. There is no randomized comparison with which to distinguish outcomes associated with the regimen from outcomes associated with patient characteristics, disease course, or other aspects of care. The registry record does not report a comparative treatment effect.

The enrollment figure is 101, but the number treated and the number included in each outcome analysis are not reported separately. Although the stated analysis population is all treated patients, the entry does not report endpoint evaluability, exclusions, missing-data handling, or sensitivity analyses. The impact of missing or unavailable assessments cannot be evaluated.

The population includes several cancer categories, and progression criteria differ by tumor type, including separate criteria for leukemia. The registry does not provide outcome estimates by diagnosis or details about review procedures, so consistency and variation in outcome assessment cannot be examined. Detailed eligibility criteria are also not reported in the registry record.

Finally, a statistical analysis plan, sample-size justification, multiplicity strategy, and interim analysis details are not reported in the registry record. The adverse-event entry lists affected counts and serious-event terms, but does not report the death count or further event-assessment details. These gaps limit both efficacy and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Etoposide, Cyclophosphamide, Thalidomide, Celecoxib, and Fenofibrate in Relapsed or Progressive Cancer — NCT00357500.
• Registry record last updated 2014-10-01; status last verified 2014-09.
• Results first posted 2014-09-09.
• 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.

19. Record Summary

This completed phase II study evaluated a single-group oral regimen of thalidomide, celecoxib, fenofibrate, etoposide, and cyclophosphamide in young patients with relapsed or progressive cancer. Dana-Farber Cancer Institute is listed as the sponsor. Enrollment was 101; the recorded start was 2005-01 and primary completion was 2013-02.

The primary endpoint was the proportion of patients alive at 27 weeks without progressive disease and having tolerated therapy. The registry specifies a 90% confidence interval but does not report the estimate or interval. Secondary outcomes named are 27-week progression-free survival, 27-week overall survival, and best response; their results are not reported in the registry record.

The record describes serious and other adverse-event counts and lists serious-event terms with percentages. It does not report a death count. A detailed analysis plan, missing-data methods, multiplicity approach, and sample-size justification are not reported in the registry record.