Dose Dense Adjuvant CMF (Cyclophosphamide, Methotrexate, Fluorouracil) at 14 and 10-11 Day Intervals for Women With Early Stage Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dose Dense Adjuvant CMF (Cyclophosphamide, Methotrexate, Fluorouracil) at 14 and 10-11 Day Intervals for Women With Early Stage Breast Cancer (NCT00615901), a na na study. The primary outcome is The Number of Patients Who Completed 8 Cycles..

2. Clinical Question

3. Trial Design

This is a completed pilot study with a single treatment cohort. The registry lists Memorial Sloan Kettering Cancer Center as the sponsor, an enrollment of 38 and breast cancer as the condition. The recorded study start is 2008-01, the primary completion is 2010-06, and the status is completed. Phase and allocation are recorded as NA; masking is recorded as none.

The arm description specifies 8 cycles of CMF at 14-day intervals, supported by PEG-filgrastim, for a cohort of 38 participants. It lists cyclophosphamide at 600 mg/m2, methotrexate at 40 mg/m2 and fluorouracil at 600 mg/m2. The title refers to 14-day and 10-11-day intervals, but the described cohort is the 14-day schedule. Results for a 10-11-day cohort are not reported in the registry record.

The study summary explains that the purpose was to test the safety of giving the drugs every 2 weeks or sooner, rather than the usual 3-week schedule described in that summary. That statement gives the motivation, not a comparative result. The recorded design does not include random assignment or a control arm, so differences between schedules cannot be estimated from this cohort alone.

The registry lists one primary outcome measure and no analysis results. Although the study status is completed, completion of the study does not by itself disclose how many participants completed the regimen, whether the stated feasibility criteria were met, or how long the cycles took.

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

Reasons for not completing this period:

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 The Number of Patients Who Completed 8 Cycles., measured over 2 years.

The primary outcome is the number of participants who completed 8 cycles of the study regimen, with a timeframe of 2 years. A completion count is a direct measure of whether participants proceeded through the planned course. In a pilot focused on a compressed treatment schedule, it can describe how often participants reached the regimen’s intended end point. By itself, however, the count does not explain why participants did or did not complete treatment, and it is not a comparison of schedules.

The registry separately describes the regimen as feasible and tolerable if participants had ANC > 1.5 on day 1 of treatment for all 8 cycles and had no grade 3 or higher non-hematologic toxicity, excluding alopecia, nausea/vomiting and bone pain. The record also says that the total number of days needed to complete all 8 cycles would be evaluated. These details indicate that completion was considered alongside blood-count and toxicity conditions, as well as treatment duration. The stated primary outcome title is a completion count; the registry does not report its observed value or results for the additional criteria.

Using a completion count is informative for a feasibility question, but it is not a measure of comparative efficacy. Without the actual count and participant-level reasons for completion or noncompletion, readers cannot assess the observed degree of feasibility from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods describe how a study turns observations into estimates and how uncertainty is assessed. For this record, the design information identifies a single cohort, while the primary outcome is a participant count. The registry lists no analysis results, so there is no reported estimate or inferential result to evaluate. The concepts below explain what such methods would mean generally; they do not imply that a particular analysis was conducted.

What does a completion count describe?

A count records how many participants meet a defined outcome. For this study, the named outcome is completion of all 8 cycles. A count can be paired with the number assessed to form a proportion, but that proportion should only be reported when its numerator and denominator are specified and the analysis population is clear. The registry gives an enrollment of 38, but it does not report the number who completed the cycles. Enrollment alone cannot be substituted for the outcome numerator.

Completion also needs an operational definition. The registry’s description includes blood-count and toxicity conditions in its definition of feasibility and tolerability, while the primary outcome title refers to the number completing cycles. Those are related but not interchangeable outcomes. An analysis should make clear whether it counts cycle completion alone, completion under the stated safety conditions, or both. The registry record does not report an analysis resolving that distinction.

What would a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimate under a specified statistical model. For a proportion, it would convey how compatible different underlying completion rates are with the observed count, subject to assumptions and the sampling process. A point estimate without an interval gives less information about precision. Neither a confidence interval nor a completion estimate is reported in the registry record, so their values cannot be interpreted for this cohort.

A confidence interval would not correct limitations in the design. It cannot create a control group, remove selection effects, or show that a schedule caused an outcome. It quantifies sampling uncertainty around a defined estimate; it does not resolve whether the estimate answers a broader causal or comparative question.

Why does the single-group design matter?

A single-group study observes participants receiving the described regimen without a concurrent comparator. Descriptive outcomes can characterize that cohort, but comparisons with another schedule require data from an appropriate comparison group and a suitable design or analysis. Since allocation is recorded as NA and there is no control arm in the design description, a randomized comparison is not part of the registry record. The study summary’s discussion of other treatment schedules is not a control condition within this study.

Even if an outcome count were reported, interpretation would depend on who entered the cohort, who was assessed, and how missing outcomes were handled. Those details are not reported in the registry record. A sample-size calculation or a narrow confidence interval would not, by itself, overcome the absence of a concurrent comparator.

How should planning illustrations be understood?

General sample-size planning asks how many participants might be needed to detect a specified effect under stated assumptions. The record’s planning description refers to a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the target effect expressed as a fraction of an observed effect. It also states that such calculations are planning illustrations, not the study’s own design. These assumptions describe a hypothetical two-arm calculation, whereas the registered study is single-group. The planning figures should therefore not be read as a description of how this cohort was designed or analyzed.

Planning sample sizes are not observed power. Observed power is not a substitute for reporting the estimate and its uncertainty after the study. In this record, the actual primary outcome count and analysis results are not reported, so a reader cannot use the endpoint results to evaluate the effect or its precision. The registry record also does not report the protocol’s sample-size justification.

Why can event counts be difficult to compare?

For adverse events, a count depends on the event definition, the time at risk, and how events are attributed and recorded. Participants may have more than one event, so a count of events need not equal a count of affected participants. The registry provides participant counts for serious and other adverse events, but detailed event-level methods are not reported. General interpretation should keep those distinct quantities separate and avoid treating an event count as a participant count unless the registry identifies it as such.

Over-dispersion is a general statistical issue that can arise when event-count variation is greater than a model expects. In that setting, a simple count model may understate uncertainty if it does not account for the extra variation. The registry record does not report an event-count model or an analysis of repeated events, so over-dispersion cannot be assessed as a feature of this study’s analysis.

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("Cohort A (CMF at 14 Day Intervals)")
n      <- c(29)
events <- c(29)
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  Cohort A (CMF at 14 Day Intervals)  29  29  100.0  88.1  100.0  88.3  100.0  88.4  99.9

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity concerns arise when a study evaluates several outcomes, time points, subgroups or statistical tests. Repeated testing can increase the chance of finding an apparently notable result by chance. The registry lists one outcome measure and no analysis results. It does not report whether there were additional prespecified outcomes, multiple comparisons, subgroup analyses or interim analyses, so the approach to multiplicity is not reported in the registry record. No adjustment or testing strategy should be inferred.

Missing data can affect a completion outcome if participants leave the study, stop treatment, or lack an assessment. The registry record does not state how missing outcome information was handled, whether all enrolled participants were included in the primary analysis, or how withdrawal and treatment discontinuation were classified. It also does not report an analysis population definition. These omissions mean that readers cannot determine from the record whether the endpoint was analyzed for every enrolled participant or only for those with an available assessment.

The enrollment of 38 is not itself an analysis denominator. The number enrolled, the number with an observed outcome and the number meeting a particular criterion can differ. Since the primary completion count is absent, the registry record does not establish the endpoint denominator or the handling of participants with unknown completion status.

The record does not report a statistical analysis plan, interim-analysis approach or missing-data sensitivity analysis. This absence limits assessment of prespecification and robustness. It does not establish that such procedures were or were not used outside the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (2.6%), seizure (2.6%), febrile neutropenia (0.0%), skin infection (0.0%).

The registry lists 38 participants at risk for serious adverse events and 2 affected participants. It separately lists 38 at risk for other adverse events and 19 affected participants. These are participant counts in the registry’s adverse-event fields; they are not the primary completion outcome, and they should not be combined into a single total because a participant may appear in more than one category.

The serious adverse-event terms listed include abdominal pain at 2.6% and seizure at 2.6%. Febrile neutropenia and skin infection are each listed at 0.0%. These term-specific percentages are registry entries, not estimates recalculated from the counts. The record does not provide further detail on event timing, duration, recurrence or participant overlap. A listed 0.0% for a term does not describe adverse events beyond that named term.

Safety counts are descriptive. They do not establish that the regimen is safe or unsafe, and they cannot be interpreted as a comparison with another schedule. The registry record does not provide a comprehensive event narrative or analysis of exposure-adjusted risk.

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

The record documents a completed pilot study intended to examine a dose-dense CMF regimen at 14-day intervals. It defines a primary endpoint based on completing all 8 cycles and describes additional feasibility and tolerability criteria. It also records adverse-event counts for the cohort. These details clarify what the study aimed to assess and what kinds of observations were registered.

The record does not report the number of participants who completed all cycles, results for the stated ANC and toxicity criteria, or the total days needed to complete treatment. It therefore does not show the observed primary outcome. It also does not report an inferential analysis or a confidence interval. Without those results, the degree of uncertainty around completion cannot be evaluated from the registry record.

The design is single-group, with no comparator. Accordingly, even a reported completion count would describe outcomes in this cohort rather than show how outcomes differ from a less frequent schedule or another treatment. The study’s summary gives a rationale for testing a shorter interval, but that rationale is not evidence of a comparative benefit. The 10-11-day schedule named in the title is not described as a cohort in the recorded arm details.

The reported adverse-event counts provide limited descriptive information. They do not answer the primary completion question, and the registry does not provide enough event detail to support a comprehensive safety assessment. The study’s completed status should be read as a status designation, not as evidence that its primary endpoint was achieved.

Overall, the registry record allows readers to identify the planned regimen, outcome definition and selected safety counts. It does not provide the outcome results needed to quantify feasibility, assess precision, or make comparisons between treatment schedules. No conclusion about comparative efficacy or treatment benefit follows from the information recorded.

14. Why This Trial Matters Statistically

This study raises statistical questions that are common in early clinical research. A pilot cohort can focus on whether a regimen can be delivered and whether participants complete a planned course. For such a purpose, the endpoint definition matters: a count of participants completing cycles differs from a combined feasibility definition that also incorporates blood-count and toxicity criteria. The registry records both kinds of information but does not report results that show how they were applied.

The single-group design also makes the boundary between description and comparison important. A cohort can describe observed outcomes in participants receiving a regimen, but it cannot by itself distinguish regimen effects from other influences. A background rationale about more frequent treatment does not replace a comparator. This distinction helps prevent readers from treating a feasibility study as a test of comparative efficacy.

Reporting completeness is central to statistical interpretation. The cohort size and study status are recorded, but the primary endpoint count, its uncertainty and the analysis population are not. Without those details, readers cannot tell how often participants completed treatment or how stable an estimate might be. Missing outcome reporting is not evidence that an outcome was poor or favorable; it leaves the question unresolved in the registry record.

The safety entries further illustrate the need to distinguish participant counts from event descriptions and to understand the level of detail behind a result. The available counts can be stated plainly, while broader claims require information the record does not provide. Keeping these distinctions clear preserves the value of a pilot study without overstating what its registered results establish.

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 interpreting this record is that the primary outcome result is not reported. Although the study is marked completed and the primary outcome is defined, the number of participants completing 8 cycles is absent. Results for the stated feasibility and tolerability criteria, and for total days to complete treatment, are also not reported in the registry record. The primary endpoint’s precision therefore cannot be assessed.

The study is described as single-group, with no comparator. Its observations cannot establish a difference between the 14-day regimen and another schedule. Although the title mentions 10-11-day intervals, the recorded arm description specifies the 14-day cohort; corresponding results for a 10-11-day cohort are not reported in the registry record.

Further details relevant to interpretation are not reported in the registry record, including the primary analysis population, handling of missing outcomes, and the statistical analysis plan. The entry does not provide participant-level reasons for discontinuation or event-level details for safety outcomes. This prevents assessment of whether missingness or variation in treatment exposure influenced the endpoint counts.

The adverse-event entries are limited to affected-participant counts and selected serious-event terms and percentages. They do not provide a full description of event timing, recurrence, duration or overlap. The cohort size is recorded as 38, but that does not tell readers how many participants contributed data to each outcome. These limitations constrain the record to a description of design and selected registered counts rather than a complete outcome analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dose Dense Adjuvant CMF (Cyclophosphamide, Methotrexate, Fluorouracil) at 14 and 10-11 Day Intervals for Women With Early Stage Breast Cancer — NCT00615901.
• Registry record last updated 2017-03-03; status last verified 2017-01.
• Results first posted 2017-03-03.
• 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

The registry record describes a completed, single-group pilot study sponsored by Memorial Sloan Kettering Cancer Center, with enrollment of 38 and breast cancer as the condition. The recorded regimen consists of 8 cycles of CMF at 14-day intervals, supported by PEG-filgrastim. The primary outcome is the number of participants completing all cycles, with a timeframe of 2 years.

The record describes feasibility and tolerability criteria involving ANC > 1.5 on day 1 of all cycles and absence of specified grade 3 or higher non-hematologic toxicity. It does not report the primary completion count or results for those criteria. Adverse-event fields list 2 of 38 participants with serious events and 19 of 38 with other events. The registry describes no comparator and reports no analysis results.