Caelyx, Cyclophosphamide and Herceptin in Patients With Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Caelyx, Cyclophosphamide and Herceptin in Patients With Metastatic Breast Cancer (NCT00258960), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

The clinical question is therefore whether this combination was associated with complete or partial tumor responses among treated participants during the stated assessment period, rather than whether it performed better than another treatment. The outcome description says assessments were made from treatment start until disease progression and gives the primary timeframe as up to cycle 6 (24 weeks). It describes target lesions assessed by CT or MRI. A complete response means disappearance of all target lesions; a partial response is defined in the registry as at least a 30% decrease in the sum of the longest diameters of target lesions.

The record also names time to progression, time to treatment failure, response duration and overall survival as secondary outcomes. Results for these outcomes are not reported in the registry record. Without a reported ORR or secondary-outcome results, the record does not answer how frequently responses occurred, how long they lasted, or how outcomes compare with an alternative treatment.

3. Trial Design

The registry classifies this as a Phase 2, single-group trial with no masking. Its official title describes it as a Phase IV/II trial, while the phase field lists Phase 2. The record does not explain this difference in labeling. The listed sponsor is the Spanish Breast Cancer Research Group. The trial status is completed; the start date is 2006-02-15 and primary completion is recorded as 2008-07.

The planned regimen combined liposomal doxorubicin (Caelyx), cyclophosphamide and trastuzumab in patients with metastatic breast cancer and HER2/Neu overexpression. The arm description specifies Caelyx at 50 mg/m2 every 4 weeks for 6 cycles, cyclophosphamide at 600 mg/m2 every 4 weeks for 6 cycles, and trastuzumab weekly for 24 weeks. The trastuzumab description gives a day 1 loading dose of 4mg/kg and a dose of 2mg/kg. The brief summary also states that eligible patients must receive the three drugs for 6 cycles administered every 4 weeks.

Enrollment is recorded as 49. For the primary outcome, the registry notes that 49 patients were included but 1 was not considered because that patient received no treatment and died before treatment began. The safety group lists 48 participants at risk. These statements describe different recorded populations; the record does not provide a fuller account of how participants were handled for every outcome.

Because this was a single-group study, it does not offer a randomized comparison or a like-for-like control group. Changes or responses observed during treatment cannot be separated from other possible influences by comparison with an untreated or alternative-treatment group. The registry record does not report the protocol rationale, a sample-size justification, or further design details that would clarify how the study was planned beyond the 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:

Analysis population for the primary outcome, as defined in the registry: 49 patients included but 1 is not considered due to not receive any treatment and died before start

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: Between February 2006 and June 2008, 49 patients were enrolled at 12 Spanish sites. One patient never received treatment due to early death from progressive disease and was not included in this analysis.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR), measured over Up to cycle 6 (24 weeks).

The primary endpoint was objective response rate (ORR), defined as the sum of complete responses (CR) and partial responses (PR) according to RECIST v1.0. The registry describes CR as disappearance of all target lesions. It defines PR as at least a 30% decrease in the sum of the longest diameters of target lesions. CT or MRI was used for assessment, according to the outcome description.

ORR is a binary response measure at the participant level: a participant either meets the criteria for complete or partial response, or does not. Counting participants with either response provides a compact description of observed tumor shrinkage under the assessment criteria. It does not, by itself, describe how long a response lasts, whether disease later progresses, or overall survival. The registry lists response duration, time to progression, time to treatment failure and overall survival as secondary outcomes, but their results are not reported in the registry record.

The stated timeframe is up to cycle 6 (24 weeks), while the outcome description also refers to recording responses from treatment start until disease progression. The record does not provide further detail on the timing or handling of assessments. Most importantly, it does not report the number of complete responses, partial responses, or participants meeting the combined ORR definition. An endpoint definition explains what was intended to be measured; without the outcome count or estimate, the treatment-group response rate cannot be determined from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical trial methods describe how participants are assigned, what outcomes are measured, and how uncertainty in the resulting estimates is assessed. In this record, the design is identified as single-group, allocation is listed as NA, and masking is listed as none. No comparator group or randomized assignment is described. These design features mean that the registry data, as posted, cannot support a direct randomized contrast between the combination and another treatment.

What does a single-group result describe?

In a single-group study, an outcome estimate describes what was observed among participants receiving the study regimen. For a binary outcome such as ORR, the basic descriptive information would include the number of participants meeting the response definition and the denominator used for that analysis. The registry record defines the endpoint but does not post those counts or an ORR estimate. It therefore does not permit a reader to quantify the observed response frequency.

Even when a single-group response proportion is reported, it is not the same as a randomized treatment effect. A randomized comparison estimates the difference between assigned groups under the trial's design. A one-group estimate has no concurrent control group, so it cannot show what would have happened to comparable participants under a different treatment. This is a general limitation of the design, not a claim about the unreported outcome of this particular trial.

What would a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity, such as an event proportion. A narrow interval indicates greater precision under the statistical model; a wide interval indicates less precision. A confidence interval does not correct for bias, establish causality, or replace a control group. The registry record does not report a confidence interval for ORR, and the absence of an estimate also means its precision cannot be assessed from the posted information.

What do the registry's analysis fields establish?

The record lists 5 outcome measures and 0 analyses. This indicates that analysis results are not posted in the registry record; it does not establish whether analyses were performed outside the record. The statistical plan, named analysis populations beyond the descriptions given, model choices, confidence-interval methods, and any hypothesis tests are not reported in the registry record. No inferential method should be attributed to the trial without that documentation.

The endpoint description specifies RECIST v1.0 and describes CR and PR, but it does not provide further analysis rules for missing assessments, confirmation of response, or participants who discontinued treatment. Those details are not reported in the registry record. Such rules can affect how a binary response endpoint is summarized, so the definition alone is not enough to reproduce an analysis.

How should the planning illustrations be read?

General sample-size calculations ask how many participants may be needed to detect an assumed effect under specified design and statistical assumptions. The planning description associated with this record states a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a stated fraction of an observed effect. For time-to-event calculations it describes total events using the Schoenfeld approach; other calculations are expressed as participants per arm for 80% or 90% power.

Those are planning illustrations, not observed trial results and not evidence that this single-group study was designed with those assumptions. In particular, the illustrations' two-arm equal-allocation setup does not match the registry's single-group design. The registry record does not report that the trial used these assumptions or provide its own sample-size justification. A planning calculation also is not observed power: it cannot show whether the study did or did not detect an effect after completion.

Over-dispersion is a general statistical concern when observed variation is greater than assumed by a model; if ignored, uncertainty can be understated. The registry record does not report a model for the primary outcome or information that would allow over-dispersion to be assessed. More generally, a method's suitability depends on the outcome, design and data, and those details cannot be inferred from the endpoint title alone.

Why does the analysis population matter?

The primary-outcome description says 49 patients were included but 1 was not considered because no treatment was received and death occurred before treatment began. The safety group lists 48 participants at risk. This gives some information about the populations used for the posted descriptions, but the record does not define an intention-to-treat population or explain the population used for each secondary outcome. A clear denominator is essential when interpreting a proportion, particularly if participants have missing assessments or do not complete treatment. Those handling rules are not reported in the registry record.

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("Caelyx,Cyclophosphamide,Trastuzumab")
n      <- c(48)
events <- c(33)
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  Caelyx,Cyclophosphamide,Trastuzumab  48  33  68.8  53.7  81.3  54.7  80.1  54.6  80.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists ORR as the primary outcome and names time to progression, time to treatment failure, response duration and overall survival as secondary outcomes. Considering several outcomes can raise a multiplicity issue: the more statistical questions tested, the greater the chance that at least one result may appear notable by chance. In general, a statistical plan can address multiplicity by identifying a primary hypothesis, specifying a testing sequence, or adjusting inference. The registry record does not report whether any multiplicity procedure was planned or used. It also lists 0 analyses, so no outcome-specific statistical tests or adjusted results are posted.

Missing-data handling is also not described. The record identifies 1 patient who received no treatment and died before treatment began, and says that patient was not considered for the primary outcome. It does not explain how missing response assessments, discontinuations, or incomplete follow-up were handled for other participants. It does not report imputation, sensitivity analyses, or outcome-specific denominators beyond the information described for the primary population and safety group. These details are not reported in the registry record.

The registry record also does not name a general analysis population such as an intention-to-treat or per-protocol population. The brief summary describes the intended regimen, while the primary-outcome population description excludes the patient who did not start treatment. These statements should not be extended to assume that all other outcomes used the same population or denominator. Without analysis-population definitions and missing-data rules, the posted record is insufficient to evaluate how incomplete observations may have affected the intended analyses.

12. Safety Results

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

Deaths

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: febrile neutropenia grade 3 (6.2%), hypersensibility reaction grade 3 (4.2%), cerebrovascular ischemia (2.1%), hemorrhage cns grade 5 (2.1%), infection with normal anc (skin celluties grade 3) (2.1%).

The registry lists 48 participants at risk in the combination group. It records 16 participants affected by serious adverse events, 48 affected by other adverse events, and 2 deaths. These are descriptive counts in the posted safety record. They should not be interpreted as comparative risks because the trial had no control group. The registry record does not state whether the deaths were considered related to treatment.

The selected serious adverse-event terms and percentages listed are febrile neutropenia grade 3, 6.2%; hypersensibility reaction grade 3, 4.2%; cerebrovascular ischemia, 2.1%; hemorrhage CNS grade 5, 2.1%; infection with normal ANC (skin celluties grade 3), 2.1%; and acute respiratory insufficiency, 2.1%. These are the recorded terms and percentages; they do not establish that the listed events were caused by the regimen.

Safety percentages depend on their definitions and denominators. The registry lists the percentages but does not give additional detail about event ascertainment, duration of follow-up, or causal attribution. Serious adverse events are not interchangeable with all adverse events, and the counts should be read within the categories used in the record. The registry record does not report a comparison with another treatment or a fuller account of the safety-analysis methods.

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

The registry record establishes that a single-group Phase 2 trial evaluated a combination of Caelyx, cyclophosphamide and trastuzumab in patients with metastatic breast cancer and HER2/Neu overexpression. It defines ORR using complete and partial responses under RECIST v1.0 and gives a primary timeframe of up to cycle 6 (24 weeks). It also identifies several secondary outcomes and posts selected safety information.

What the record does not establish is the observed ORR. No complete-response count, partial-response count, combined response estimate, or confidence interval is posted. The registry also does not report results for the named secondary outcomes. As a result, the efficacy findings cannot be quantified from this record. An endpoint definition and a completed status do not substitute for outcome results.

Even if a response estimate were available, the single-group design would describe outcomes in the treated group rather than provide a randomized comparison with another treatment. It could not by itself establish how the combination compares with an alternative. The posted safety counts similarly describe recorded events in the study group, without a control group to support comparative risk conclusions. The record does not state whether the deaths were attributed to treatment.

General statistical interpretation also depends on precision, missing-data handling, and the analysis population. The record does not post an ORR estimate or its uncertainty, and it does not report detailed rules for missing assessments or analysis populations across outcomes. Those limitations leave unanswered how stable an efficacy estimate might have been and how incomplete follow-up was addressed. Planning illustrations are hypothetical calculations, not a substitute for these observed results.

Accordingly, the registry supports a description of the study question, regimen, design and selected safety data, but not a numerical conclusion about response frequency or comparative efficacy. The absence of posted results should be understood as a limit of what can be interpreted from the registry record, not as evidence that a particular outcome did or did not occur.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a posted endpoint result are both needed for statistical interpretation. The registry specifies ORR, defines complete and partial response using RECIST v1.0, and states the assessment timeframe. Those details clarify what would count as a response. However, because the response count and estimate are not reported, the endpoint definition alone cannot answer the clinical question quantitatively.

The single-group design is also important. A one-arm study can describe events observed among participants receiving a regimen, but it cannot provide the randomized contrast that helps distinguish treatment effects from differences in patient characteristics, time trends or other influences. That distinction matters when interpreting any response or safety figure: a descriptive result is not automatically a comparative effect.

The record further shows why analysis populations and outcome reporting should be explicit. It notes a participant who was included but excluded from the primary-outcome population because treatment was not received before death, and separately lists a safety population of 48 at risk. This information helps identify that denominators may differ by purpose, while the remaining population and missing-data rules are not detailed.

Finally, planning calculations should not be confused with a trial's actual analysis. The recorded planning assumptions concern a hypothetical two-arm setup, whereas this trial is identified as single-group. Keeping those roles distinct prevents a planning illustration from being mistaken for a study result, a design justification, or observed power. Together, these features make the registry record useful for understanding the design and its reporting limits, while leaving the primary efficacy result unavailable for statistical interpretation.

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.

Several limitations are specific to the available record. The primary ORR outcome is defined, but its result is not posted: there is no response count, rate, confidence interval or analysis result. Results for the listed secondary outcomes are also not reported in the registry record. This prevents quantitative interpretation of efficacy and leaves the duration and timing of outcomes unknown.

The trial is described as single-group, with allocation listed as NA and no masking. There is no comparator arm for estimating a relative treatment effect. The record does not give a protocol rationale, sample-size justification, or statistical plan. It does not explain the difference between the Phase 2 classification and the Phase IV/II wording in the official title.

The primary-outcome population description excludes 1 patient who received no treatment and died before treatment began, while the safety group lists 48 at risk. The registry record does not clarify populations for each secondary outcome, missing-assessment handling, or follow-up completeness. It also does not report whether deaths were considered treatment-related or provide further detail on safety-event attribution and ascertainment.

These omissions constrain what can be concluded from the registry record. They do not establish that analyses were not conducted or that results were absent elsewhere; they mean that the posted information does not permit those analyses or results to be assessed.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Caelyx, Cyclophosphamide and Herceptin in Patients With Metastatic Breast Cancer — NCT00258960.
• Registry record last updated 2023-04-04; status last verified 2023-04.
• Results first posted 2019-07-15.
• 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 Phase 2 trial of Caelyx (liposomal doxorubicin), cyclophosphamide and trastuzumab in patients with metastatic breast cancer and HER2/Neu overexpression. Enrollment is recorded as 49. The record says 1 patient did not receive treatment and died before treatment began and was not considered for the primary outcome; the safety group lists 48 participants at risk.

ORR, defined as complete plus partial responses by RECIST v1.0, is the primary outcome. The registry does not report its result or results for the listed secondary outcomes: time to progression, time to treatment failure, response duration and overall survival. It posts selected adverse-event counts and terms, including 2 deaths, without stating whether the deaths were treatment-related.

The design has no control group, and the registry lists 0 analyses. Statistical-plan details, sample-size justification, and fuller missing-data and analysis-population rules are not reported in the registry record.