Adjuvant Doxorubicin/Cyclophosphamide and Paclitaxel Plus Sorafenib Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adjuvant Doxorubicin/Cyclophosphamide and Paclitaxel Plus Sorafenib Breast Cancer (NCT00544167), a na na study. The primary outcome is The Safety and Tolerability of Protocol Treatment, Defined as the Percentage of Patients Experiencing Severe or Life-threatening Side Effects Per CTCAE Version 3.0..

2. Clinical Question

The study asked whether protocol treatment combining standard chemotherapy with sorafenib could be assessed for safety and tolerability in women with node-positive or otherwise high-risk early-stage breast cancer. It was described as a pilot study, with the stated aim of assessing severe or life-threatening side effects. The primary endpoint was defined as the percentage of patients experiencing such side effects according to CTCAE Version 3.0, with an 18 Months timeframe.

The stated motivation was to assess whether the combined regimen was tolerable and could provide a rationale for further study in a larger randomized design. That rationale is not itself evidence of comparative benefit. Because the study had no control group, its design addresses an early safety question rather than a causal comparison between treatment strategies.

3. Trial Design

This was a completed, single-group pilot study sponsored by SCRI Development Innovations, LLC. The registry lists an enrollment of 45, phase NA, allocation NA, and masking NONE. The study start is recorded as 2007-05 and primary completion as 2008-01. These record details describe the registered study; they do not establish how many participants completed every treatment component or contributed data to each outcome.

All patients were assigned the same general treatment sequence: doxorubicin and cyclophosphamide, followed by paclitaxel combined with sorafenib. The registry gives the doxorubicin and cyclophosphamide doses and schedule, and lists two paclitaxel schedules, with the choice left to physician discretion. The intervention description ends before the full regimen details are available, so further dosing, duration, or treatment-modification rules are not reported in the registry record.

A single-group design can describe outcomes observed among participants receiving the study regimen. It cannot by itself separate the regimen’s effects from the course of the disease, participant characteristics, other care, or chance. There is no randomized or concurrent comparator in this record, and its allocation is listed as NA; comparisons with an external group would not be a like-for-like control comparison.

The study’s stated focus was safety and tolerability, not a comparative efficacy test. Its primary endpoint concerns the percentage experiencing severe or life-threatening side effects under CTCAE Version 3.0 over 18 Months. The registry record does not report a numerical result for that endpoint, an analysis estimate, or an analysis population. Although the status is COMPLETED, that status does not supply missing outcome results or establish which participants contributed to the primary endpoint.

The registry record does not report a statistical analysis plan, a sample-size justification, interim-analysis procedures, or rules for handling treatment discontinuation. Those omissions limit how fully the design can be reconstructed from the registration information.

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 Safety and Tolerability of Protocol Treatment, Defined as the Percentage of Patients Experiencing Severe or Life-threatening Side Effects Per CTCAE Version 3.0., measured over 18 Months.

The primary endpoint is the percentage of patients experiencing severe or life-threatening side effects, defined using CTCAE Version 3.0, over the stated timeframe of 18 Months. It is a binary participant-level outcome: each participant either meets the endpoint definition or does not. A percentage is intended to express how common the defined event was in the population assessed, but interpreting it requires a clearly reported event count and denominator.

A safety and tolerability endpoint is relevant in a pilot study of a new combination because it describes adverse effects during the treatment strategy being evaluated. It can help characterize what was observed in the study group and inform questions for later research. It does not, on its own, establish that the regimen caused each event, nor does it show whether the frequency differs from another treatment strategy.

The registry names the endpoint and its assessment timeframe, but does not report the percentage, the number meeting the endpoint definition, a confidence interval, or details about the assessment population. The serious adverse-event counts recorded separately cannot be substituted for the primary endpoint: serious-event classification and severe or life-threatening side-effect grading are not necessarily the same definition. The registry record does not establish that the listed serious adverse events all met the primary endpoint criteria.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a proportion: the number of participants meeting the stated side-effect definition divided by the number assessed for that endpoint. In general, a proportion is interpretable only when both the event definition and the analysis denominator are clear. Here, the registry specifies severe or life-threatening side effects under CTCAE Version 3.0 and an 18 Months timeframe, but does not report the endpoint count, percentage, or analysis denominator. The listed enrollment does not automatically establish the denominator for the endpoint, because eligibility, treatment exposure, follow-up, and analysis inclusion can differ.

What does a confidence interval communicate?

In general, a confidence interval expresses statistical uncertainty around an estimate. For a proportion, it helps show how compatible the observed data are with a range of underlying event rates, subject to the method and assumptions used. A narrow interval generally indicates greater precision than a wide interval, while neither width nor location establishes causality. No confidence interval for the primary endpoint is reported in the registry record, so precision for that outcome cannot be assessed from this record.

For binary outcomes, common approaches use binomial models or approximations to estimate a proportion and its uncertainty. These are general methods, not methods identified as having been used in this study. Choice of approach can matter, especially when event counts are small or the observed proportion is near a boundary. The registry record does not name the estimator, interval method, or statistical software, so it is not possible to attribute a particular method to the sponsor.

Why do endpoint definitions matter?

Safety outcomes can be classified along different dimensions. A participant-level endpoint may define whether a person experienced at least one qualifying event, while an event-level summary may count event occurrences or list event types. Those summaries answer different questions. In general, a serious adverse event category and a severity-grade category need not coincide. A serious event may not be the same as a severe or life-threatening event under a toxicity grading system, and a participant can potentially contribute to more than one event category. The record does not explain how its serious adverse-event listings map to the primary CTCAE endpoint.

The registry’s adverse-event entries report 7 affected among 45 at risk for serious adverse events, and 45 affected among 45 at risk for other adverse events. These figures should be read using the labels and denominators attached to those entries. They should not be combined, converted into a different endpoint, or treated as the primary outcome without a definition establishing that equivalence. The record gives no participant-level data with which to examine event overlap or timing.

What can a single-group design estimate?

In general, a single-group study can describe the outcomes observed in the enrolled study group. It does not provide a concurrent counterfactual: the outcome that the same kinds of participants would have experienced under a different treatment strategy. Randomization in a comparative study is one way to support a more credible treatment contrast, but this study has no separate control group and its allocation is listed as NA. Consequently, an observed event frequency in this group cannot establish the difference attributable to adding sorafenib or to any other component of the regimen.

The intervention description also allows physician discretion between two paclitaxel schedules. In general, variation in treatment exposure can affect how outcomes are interpreted, particularly when details of treatment changes, adherence, and follow-up are not available. The registry record does not provide those details, so it is not possible to assess their role in the reported adverse-event counts.

How should planning calculations be read?

The registry describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. Such calculations are planning illustrations, not observed power and not results from the trial. The registry’s study itself is single group, so an equal-allocation, two-arm planning setup should not be mistaken for the trial’s actual design. The record does not report a sample-size justification for the pilot study, and the planning description does not establish that this was the method used to choose the study enrollment.

More generally, sample-size calculations depend on the outcome, target effect, variability, significance level, power target, allocation, and analysis method. Changing assumptions can change a planning estimate. A planning illustration based on an observed effect is especially dependent on that estimate and is not independent evidence that the effect is real or reproducible. No numerical planning outputs or analysis results for the primary endpoint are reported in the registry record.

What cannot be assessed without an analysis plan?

The registry record does not report how missing safety observations were handled, whether the endpoint used an intention-to-treat or another analysis population, or how participants who discontinued treatment were classified. These choices can affect both the numerator and denominator of a proportion. It also does not report prespecified handling of multiple outcomes, subgroup analyses, or interim looks at accumulating data. Those methods should not be inferred from the study’s pilot designation or from its completion status.

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("Doxorubicin/Cyclophosphamide Then Paclitaxel/Soraf")
n      <- c(45)
events <- c(18)
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  Doxorubicin/Cyclophosphamide Then Paclitaxel/Soraf  45  18  40.0  25.7  55.7  27.0  54.5  27.0  54.6

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome measure, concerning the percentage of patients experiencing severe or life-threatening side effects, and lists no analyses. It does not report a multiplicity strategy, such as how statistical error would be managed across multiple endpoints, comparisons, subgroups, or repeated analyses. The absence of a reported strategy does not establish that no additional analyses were conducted; it means the approach is not reported in the registry record.

The primary endpoint result itself is not reported. The registry also does not provide an analysis population, a count meeting the primary endpoint definition, or a denominator for that endpoint. Although the record lists an enrollment of 45 and adverse-event denominators of 45 at risk, those details do not establish that all enrolled participants were included in the primary endpoint analysis or completed the relevant follow-up.

Missing-data handling is not reported in the registry record. In general, missing follow-up can affect a safety proportion if participants with incomplete observation differ from those with complete observation. An analysis plan may specify whether such participants are included, excluded, or handled under another rule; no such rule is reported. The record also does not describe withdrawals, losses to follow-up, or how participants who stopped treatment were considered for safety assessment.

These omissions matter because the endpoint is defined over 18 Months, and interpretation depends on knowing who was assessed over that timeframe and how incomplete data were treated. The listed adverse-event counts remain descriptive entries, but they do not fill in the missing primary analysis details.

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: cardiac ischemia/infarction (2.2%), pancreatitis (2.2%), infection - pneumonia (2.2%), abcess of bartholin's cyst (2.2%), hemmorhage - gi (2.2%).

The registry reports 7 participants affected by serious adverse events among 45 at risk. It separately reports 45 participants affected by other adverse events among 45 at risk. These are two differently labelled entries and should not be treated as interchangeable measures or combined into a single count. The record does not explain whether participants appear in both entries.

The serious adverse-event terms listed are Cardiac ischemia/infarction, Pancreatitis, Infection - pneumonia, Abcess of Bartholin's cyst, Hemmorhage - GI, and Infection - Streptococcus. Each term is recorded as 2.2%. These percentages should be read as the registry’s term-specific entries, not as a comparative risk or as proof that the treatment caused the events. The record does not report detailed event timing, participant-level overlap, or severity grades for each term.

Serious adverse events are not necessarily equivalent to the primary endpoint’s severe or life-threatening side effects. The primary endpoint is defined using CTCAE Version 3.0 over 18 Months, while the posted adverse-event counts do not explicitly state that same definition. The primary endpoint result is not reported in the registry record, so these adverse-event entries cannot be used as a substitute for it.

Because the study is single group, the counts describe events recorded among participants in this study; they do not estimate how the counts would differ under a control regimen.

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

The registry record establishes that a pilot study was conducted to assess safety and tolerability for a chemotherapy regimen combined with sorafenib in women with node-positive or otherwise high-risk early-stage breast cancer. It describes a single-group design and lists adverse-event counts. Those details make the record useful for understanding the study’s stated question and the safety information it chose to report.

The record does not report the result for the primary endpoint: the percentage of patients experiencing severe or life-threatening side effects according to CTCAE Version 3.0 over 18 Months. It therefore does not show a numerical estimate for the central safety and tolerability question, nor its precision. The separate serious and other adverse-event entries cannot fill that gap because the registry does not say they use the same definition as the primary endpoint.

The adverse-event listings do not establish causation. In a single-group study, observed events can be described among participants, but there is no concurrent control group for separating treatment-related effects from other explanations. The design also cannot estimate a comparative effect against another regimen. The registry record does not report randomized allocation or a like-for-like comparator.

The study’s stated purpose was to assess tolerability and provide a rationale for possible further study in a larger randomized fashion if the regimen proved tolerable. A pilot study’s stated purpose is not a conclusion about effectiveness, and the record’s completion status does not supply an unreported outcome. No claim about comparative efficacy or a treatment effect follows from the information reported.

In general, a more complete interpretation of a safety endpoint would require its event count, analysis denominator, follow-up completeness, and an uncertainty estimate, along with clarity about the analysis population and missing data. These details are not reported for the primary endpoint. The appropriate reading is therefore narrow: the registry describes the study design and records adverse-event entries, while leaving the primary safety endpoint result and its precision unreported.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly stated endpoint and a reported endpoint result are both necessary. The registry defines a safety question in concrete terms: the percentage experiencing severe or life-threatening side effects under CTCAE Version 3.0 over 18 Months. Yet it does not report that percentage, the qualifying event count, or an uncertainty estimate. A precise endpoint definition cannot answer the research question when its result is absent.

It also highlights the distinction between a pilot study’s descriptive role and a comparative treatment evaluation. A single-group pilot can document outcomes observed during a regimen and help identify questions for further research. It cannot provide a randomized comparison, and its observed adverse-event counts do not reveal what would have happened under another treatment strategy. The registry itself describes a possible rationale for later randomized study, rather than a like-for-like comparison in this study.

Safety terminology matters statistically as well as clinically. The primary outcome uses a severe or life-threatening side-effect definition, while the separate safety entries refer to serious adverse events and other adverse events. Without a reported mapping between these categories, treating one as the result for another can create a misleading interpretation. Clear definitions, denominators, analysis populations, and follow-up information are essential for understanding a proportion.

Finally, the record shows why study completion and outcome reporting should be distinguished. The study is marked COMPLETED, but the primary endpoint result and analysis details are not reported. For clinical researchers, the distinction is important: registration details describe the intended question and design, whereas an interpretable finding requires outcome data and a transparent account of how they were analyzed.

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 trial-specific limitation is the absence of a reported result for the primary safety and tolerability endpoint. The record defines the endpoint as the percentage of patients experiencing severe or life-threatening side effects under CTCAE Version 3.0 over 18 Months, but gives no endpoint estimate, qualifying count, denominator, or confidence interval. The serious adverse-event figures cannot be assumed to represent that endpoint.

The single-group design has no concurrent control arm. It can describe events observed among participants receiving the regimen but cannot establish comparative safety or attribute observed events to a particular treatment component. The registry lists allocation as NA and the study model as SINGLE GROUP, so there is no like-for-like control comparison recorded.

The intervention description includes physician discretion between two paclitaxel schedules, while the available description does not provide the full regimen details after the combined-treatment wording. The record does not report treatment adherence, modifications, discontinuations, or participant-level exposure. These gaps limit interpretation of which treatment participants actually received over time.

The adverse-event entries do not resolve the primary-outcome gap. The registry does not explain how serious adverse events relate to severe or life-threatening CTCAE side effects, whether participants overlap across categories, or when events occurred. It also does not report the completeness of safety follow-up or the approach to missing observations.

Further limitations of interpretation arise because the registry does not report an analysis population, a statistical analysis plan, multiplicity procedures, or a sample-size justification. The listed planning assumptions concern an illustration and should not be read as the pilot study’s design rationale or as evidence of observed power. These omissions prevent a fuller assessment of the statistical methods and precision.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Adjuvant Doxorubicin/Cyclophosphamide and Paclitaxel Plus Sorafenib Breast Cancer — NCT00544167.
• Registry record last updated 2013-04-01; status last verified 2013-03.
• Results first posted 2013-01-25.
• 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 describes a completed, single-group pilot study of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel combined with sorafenib in women with node-positive or otherwise high-risk early-stage breast cancer. Enrollment is listed as 45. The study was sponsored by SCRI Development Innovations, LLC, with a start recorded as 2007-05 and primary completion as 2008-01.

The primary endpoint was the percentage of patients experiencing severe or life-threatening side effects according to CTCAE Version 3.0 over 18 Months. Its result is not reported in the registry record. The record separately lists serious adverse events affecting 7 among 45 at risk and other adverse events affecting 45 among 45 at risk, along with six serious adverse-event terms recorded at 2.2% each.

There is no separate comparator group, and the record does not report analyses, a primary endpoint estimate, an uncertainty interval, missing-data methods, or an analysis population. The adverse-event entries are descriptive and do not establish a comparative treatment effect or substitute for the unreported primary endpoint.