A Study to Evaluate the Effect of HER2 Activation on rhuMAb 2C4 (Pertuzumab) in Subjects With Advanced Ovarian Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Effect of HER2 Activation on rhuMAb 2C4 (Pertuzumab) in Subjects With Advanced Ovarian Cancer (NCT00058552), a registered phase 2 study. The primary outcome is Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or Cancer Antigen 125 (CA-125) Changes.

2. Clinical Question

The study's stated purpose was to evaluate pertuzumab in people whose advanced ovarian cancer was refractory to, or had recurred after, prior chemotherapy. The record describes response assessment at screening, at specified cycles, and at follow-up 30 days after the last dose. It also lists progression-free survival, time to progression-free survival, response duration, death, overall survival, and progression-free status at specified time points as secondary outcomes; numerical results for these outcomes are not reported in the registry record.

3. Trial Design

The registry describes a Phase II, open-label, multicenter study of pertuzumab in advanced, refractory or recurrent ovarian cancer. It lists the study as completed, with a start date of 2003-05 and primary completion in 2004-07. The recorded enrollment is 129. The listed intervention is pertuzumab (rhuMAb 2C4), with dose groups titled Pertuzumab 420 mg and Pertuzumab 1050 mg.

Open-label means treatment masking was not used; the registry records masking as none. The record does not state how participants were allocated to the dose groups. It also does not identify a separate untreated or active-treatment comparator. The dose groups therefore should not be read as randomized treatment arms or as a controlled comparison. Differences between them could reflect factors beyond dose, and the registry record does not provide the information needed to assess those factors.

The primary outcome was the percentage of participants with a best overall response of complete response or partial response, determined using RECIST v1.1 or CA-125 changes. The recorded efficacy population consisted of participants who received at least 1 dose and either had a postbaseline response assessment or died within 30 days of their last treatment before a response evaluation. The response schedule included screening and assessments before infusion at Cycles 3, 5, 7, 9, 13, and 17, plus follow-up 30 days after the last dose.

Secondary outcomes listed in the record included progression or death, median time to progression, duration of response, death, overall survival, and Kaplan-Meier estimates of freedom from progression at 3, 6, and 12 Months. These entries indicate the outcome areas the record tracked, but numerical results are not reported in the registry record. Details of other design features, including eligibility criteria beyond the disease description, 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy Analysis Population: All participants who received at least 1 dose of study drug and either underwent at least one postbaseline assessment of response or died within 30 days after the last study treatment before any evaluation of response.

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: All the participants who received at least 1 dose of study drug were included in the analysis.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) Determined by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 or Cancer Antigen 125 (CA-125) Changes, measured over Screening and prior to infusion at Cycles 3, 5, 7, 9, 13, and 17 and at follow-up (30 days after the last dose of pertuzumab).

The primary endpoint was the percentage of participants whose best overall response was complete response (CR) or partial response (PR). It combined two response-assessment approaches, chosen according to whether disease was measurable at baseline: RECIST v1.1 for measurable disease and CA-125 changes for non-measurable disease. The record defines a response as documented and confirmed by two consecutive investigator assessments at least 28 days apart.

Under RECIST v1.1, CR required disappearance of all target and non-target lesions and normalization of the tumor marker level. PR required at least a 30% decrease in the sum of the longest diameters of target lesions relative to the baseline sum. Under the CA-125 approach, CR required a decrease to within normal limits and < 40 IU/mL, with no clinical or radiological evidence of disease. PR required a > 50% decrease in CA-125 from baseline and no clinical or radiological evidence of new lesions.

A response percentage is a binary-outcome summary: each participant in the efficacy population is classified according to whether the defined response was achieved. This type of endpoint can describe the frequency of observed tumor response without, by itself, describing how long a response lasts or whether survival changes. Those questions are addressed by separate time-to-event outcomes listed as secondary endpoints. The response estimate and its 95% confidence interval are not reported in the registry record, so the magnitude and precision of the primary result cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a proportion: participants are categorized as having or not having a confirmed CR or PR, and the intended summary is the percentage meeting the response definition. This is a binary endpoint because it records whether an event—in this case, qualifying response—occurred. For a binary outcome, the estimate describes the observed frequency in the defined analysis population. It does not convey the timing of response or its duration. The numerical estimate is not reported in the registry record.

What does the confidence interval describe?

The registry identifies a 95% confidence interval as the measure of dispersion for the primary endpoint, but it does not report the interval's numerical limits. In general, a confidence interval communicates statistical uncertainty around an estimated quantity. It reflects how compatible a range of values is with the data and the method used to calculate the interval. It is not a guarantee that the true value lies within the interval, and it does not resolve design limitations such as the absence of random allocation. Without the response estimate and its interval, neither the observed response frequency nor its statistical precision can be evaluated from this record.

Why does the response definition matter?

The registry requires documented and confirmed response on two consecutive investigator assessments at least 28 days apart. Requiring confirmation distinguishes a sustained assessment finding from an unconfirmed observation, although the record does not report the response counts at individual assessments. RECIST v1.1 uses changes in tumor lesions for measurable disease, whereas the CA-125 criteria use biomarker changes for non-measurable disease. Because the criteria differ, the overall proportion combines classifications made through distinct assessment routes. The registry does not report the number assessed by either route or separate route-specific response estimates.

How should the secondary outcomes be understood?

Progression-free survival is a time-to-event outcome that considers time until progression or death, as specified by the endpoint. Median time to progression-free survival is a summary of the event-time distribution. Kaplan-Meier estimates describe the estimated proportion remaining free of the event over time while accounting for differing follow-up, under the method's assumptions. Duration of response concerns time among those who responded, while overall survival concerns time until death. These are general descriptions of the statistical concepts; the numerical results for these outcomes are not reported in the registry record. The record's named secondary endpoints should not be mistaken for posted estimates.

What do planning calculations mean?

Any sample-size calculations presented with the results are planning illustrations, not observed power. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the target effect is expressed as a stated fraction of the observed effect. Such calculations explore how a hypothetical future study might be sized under chosen assumptions. They do not show that the completed study had a particular probability of detecting an effect, and they do not add evidence about the outcomes that were observed. The registry does not report the trial's own sample-size justification, so the planning illustrations should not be attributed to its design.

Equal allocation is an assumption in the planning illustration, not a description of actual allocation. The registry does not state how participants entered the 420 mg and 1050 mg groups. Because the groups are not a randomized, like-for-like control comparison, planning calculations based on equal allocation should not be used to imply that the trial was designed as a randomized comparison. The posted record lists enrollment as 129, but the analysis population size for the primary endpoint is not reported in the registry record.

What statistical details are absent?

The registry record lists no posted analyses. It does not report the primary response estimate, its confidence interval limits, numerical secondary outcome results, or an inferential comparison between dose groups. A statistical analysis plan, multiplicity adjustment, interim analysis procedures, and missing-data methods are not reported in the registry record. These omissions matter because they prevent assessment of how outcomes were analyzed, whether multiple outcome testing was addressed, and how incomplete follow-up or missing assessments influenced the reported results. Statistical methods can describe the meaning of planned summaries, but they cannot recover absent outcome data or determine which unreported analysis choices were made.

In general, over-dispersion matters when observed variability exceeds what a statistical model assumes; standard errors and uncertainty intervals can then be too narrow if that extra variability is ignored. The registry does not report an over-dispersion analysis for this study, and the primary endpoint is a binary response rather than a count outcome. No claim about whether over-dispersion was assessed can be made from the record. More broadly, the precision and validity of an estimate depend on the data, analysis population, measurement process, and model assumptions. The available record states endpoint definitions but does not provide the primary numerical estimate needed to assess those properties.

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("Pertuzumab 420 mg", "Pertuzumab 1050 mg")
n      <- c(55, 62)
events <- c(2, 3)
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  Pertuzumab 420 mg  55  2  3.6  0.4  12.5  1.0  12.3  1.1  12.3
ARM  Pertuzumab 1050 mg  62  3  4.8  1.0  13.5  1.7  13.3  1.8  13.3

11. Multiplicity, Missing Data and Analysis Populations

The record lists one primary response endpoint and several secondary outcomes. It does not report whether or how multiplicity was handled. In general, evaluating multiple outcomes or multiple comparisons can increase the chance of a nominally notable result arising by chance if no adjustment or hierarchy is used. That general concern does not establish that any particular analysis was performed or that an error occurred in this study. The registry record lists zero posted analyses, so no multiplicity procedure can be verified.

The primary efficacy population is defined as participants who received at least 1 dose and either had at least one postbaseline response assessment or died within 30 days after the last study treatment before any response evaluation. The number included in this population is not reported in the registry record. The record does not state how missing assessments, withdrawals, or other incomplete data were handled. It also does not report whether all participants in this population had evaluable response data.

The definition of the efficacy population should not be mistaken for a complete account of the analysis. The registry lists the population criteria, but does not provide an analysis flow, missing-data method, or numerical primary result. It likewise does not report an interim-analysis plan or statistical analysis plan. Any more detailed account of multiplicity, missingness, or analysis conduct is therefore not reported in 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: small intestinal obstruction (13.1%), intestinal obstruction (3.3%), abdomial pain (3.3%), ascites (3.3%), diarrhoea (3.3%).

The adverse-event listing gives serious adverse events for the Pertuzumab 420 mg group as 26 affected among 61 at risk, and for the Pertuzumab 1050 mg group as 18 affected among 62 at risk. For other adverse events, the listing gives 61 affected among 61 at risk and 60 affected among 62 at risk, respectively. These are group-level counts as recorded; they do not establish a causal effect of pertuzumab or permit a controlled comparison between dose groups.

The registry lists small intestinal obstruction at 13.1% among the top serious-event terms. Intestinal obstruction, Abdomial pain, ascites, diarrhoea, and vomiting are each listed at 3.3%. The record does not give the denominators or additional event-level detail for those percentages in this listing. Serious-event terms can overlap within participants, so the listed percentages should not be added to create a combined rate.

The group summary shows deaths as null, rather than giving a numerical count. This is not evidence of zero deaths. Although death is also named as an outcome, its numerical result is not reported in the registry record. Because allocation is not stated and no randomized control group is identified, the adverse-event figures are descriptive rather than a like-for-like safety comparison.

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

The record establishes what the investigators intended to measure: confirmed complete or partial response using disease-appropriate RECIST v1.1 or CA-125 criteria. It also identifies the efficacy population and lists secondary outcomes. These details clarify the endpoint definitions, but the numerical primary response result and its 95% confidence interval are not reported in the registry record. The posted results therefore do not establish the observed response frequency or how precisely it was estimated.

The study is recorded as completed and Phase II, with pertuzumab dose groups of 420 mg and 1050 mg. Completion and enrollment describe the conduct recorded in the registry; neither indicates the direction or size of an outcome. The record does not state allocation and cautions that the groups are not a randomized, like-for-like control comparison. Consequently, the dose listings do not support a causal claim about differences between groups.

The secondary outcome names likewise do not supply evidence about progression-free survival, response duration, or overall survival. Numerical results for these outcomes are not reported in the registry record. The adverse-event counts and listed serious-event terms provide descriptive safety information, but the record's missing death counts and lack of a controlled comparison limit what can be inferred from them.

In general, a trial result needs both an estimate and information about its uncertainty and analysis context. Here, the registry provides detailed response criteria but not the numerical response estimate, analysis population size, or missing-data approach. This limits assessment of magnitude, precision, and potential bias. The appropriate statistical reading is therefore bounded: the record describes the study question, endpoint definitions, and some adverse-event summaries, while its posted results do not allow the primary efficacy outcome or the named secondary outcomes to be quantified.

14. Why This Trial Matters Statistically

This record illustrates why endpoint definitions and outcome results need to be read separately. It specifies a confirmed-response endpoint, including two distinct assessment routes based on measurable or non-measurable disease at baseline. That level of definition helps clarify what would count as a response. Yet without a numerical response estimate and confidence interval, readers cannot learn how often the endpoint was met or how uncertain the estimate was.

The study also illustrates a limitation of comparing dose groups without documented random allocation. The registry lists 420 mg and 1050 mg groups, but says the comparison is not randomized and the groups are not like-for-like controls. A numerical contrast, even if present, would not by itself isolate the effect of dose. In this record, numerical efficacy outcomes by group are not reported in any case.

Finally, the distinction between outcome names and outcome results is important for registry interpretation. Several clinically relevant time-to-event outcomes are listed, but their values are absent. The safety summary gives event counts and selected serious-event terms, yet does not provide a randomized control comparison or a death count. These features make the record useful for identifying what was studied and what was planned to be measured, while also showing why a registry entry with outcome definitions alone cannot answer the efficacy questions quantitatively.

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 most direct limitation for interpretation is that numerical results for the primary endpoint are not reported in the registry record. The response percentage and its 95% confidence interval are absent, as are numerical results for the listed secondary outcomes. Without those estimates, the size and precision of the observed outcomes cannot be assessed.

The record identifies dose groups but does not state allocation, and it cautions that the study is not a randomized comparison. It does not identify a like-for-like control group. Thus, the groups cannot be treated as randomized dose comparisons. The registry also does not report the analysis population size, results by response-assessment method, or a flow of participants through assessment.

Although the efficacy population is defined, missing-data methods and the handling of participants without evaluable response are not reported in the registry record. The statistical analysis plan, multiplicity approach, interim analyses, and the trial's own sample-size justification are also not reported. The group adverse-event listing contains a null death value rather than a numerical count, and event-term denominators are not specified in that listing. These limitations constrain both efficacy and safety interpretation; they do not establish that unreported events or analyses were absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Evaluate the Effect of HER2 Activation on rhuMAb 2C4 (Pertuzumab) in Subjects With Advanced Ovarian Cancer — NCT00058552.
• Registry record last updated 2017-03-08; status last verified 2017-01.
• Results first posted 2015-06-23.
• 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 Phase II, open-label, multicenter study of pertuzumab in advanced, refractory or recurrent ovarian cancer. It records enrollment of 129, a start date of 2003-05, and primary completion in 2004-07. The listed dose groups are Pertuzumab 420 mg and Pertuzumab 1050 mg; allocation is not stated, and the groups are not a randomized, like-for-like control comparison.

The primary endpoint was the percentage with confirmed CR or PR under RECIST v1.1 or CA-125 criteria. Numerical primary and secondary outcome results are not reported in the registry record. The adverse-event listing includes serious and other event counts and selected serious-event terms, but the group death value is null. The record lists zero posted analyses.