Clinical Trial of PM00104 (Zalypsis®) in Patients With Advanced and/or Metastatic Endometrial or Cervical Cancer Previously Treated With One Line of Systemic Chemotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Trial of PM00104 (Zalypsis®) in Patients With Advanced and/or Metastatic Endometrial or Cervical Cancer Previously Treated With One Line of Systemic Chemotherapy (NCT00900562), a na phase 2 study. The primary outcome is Overall Response Rate (ORR).

2. Clinical Question

The study also set out to evaluate safety and pharmacokinetic and pharmacogenomic profiles. Listed secondary outcomes include best tumor response, progression-free survival, progression-free survival rate at 4 months, overall survival, and plasma pharmacokinetic parameters at the first and second infusion. Those outcomes provide additional types of information, but the registry record lists no analyses. Without outcome estimates, the central statistical question is what the design and endpoint could measure, rather than whether a response was observed or how it compared with an alternative.

3. Trial Design

This is a Phase II clinical and pharmacokinetic trial of PM00104 (Zalypsis®). The registry record lists 19 enrolled participants and a single-group model, with Zalypsis (PM00104) as the sole arm. Allocation is not applicable, and masking is none. Thus, the record describes a treated cohort without a randomized control group or blinded treatment assignment.

The target population was patients with advanced and/or metastatic endometrial or cervical cancer previously treated with one line of systemic chemotherapy. The registry record identifies both cancers as study conditions. Safety information is separated into Endometrial Cancer and Cervical Cancer groups. The study was sponsored by PharmaMar. Its recorded start was 2009-08, and its primary completion was 2011-09. Its status is terminated; the reason for termination is not reported in the registry record.

The primary outcome is overall response rate, defined using complete and partial responses under RECIST v.1.0. The stated assessment schedule was baseline and every other cycle (± 1 week) until evidence of progression, up to 2 years. Secondary outcomes cover best tumor response, progression-free survival, progression-free survival rate at 4 months, overall survival, and plasma pharmacokinetic measures at the first and second infusion. The study summary also describes an aim to determine safety, pharmacokinetic, and pharmacogenomic profiles.

A single-group design can describe outcomes observed among people receiving the study drug, but it cannot by itself estimate a randomized treatment contrast. Differences between patients, disease groups, or outcomes over time do not create a concurrent control comparison. The registry record does not report a statistical analysis plan, randomization procedure, or masking beyond the listed design characteristics. It also lists no analyses, so the design description should not be mistaken for evidence that a particular statistical method was used.

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: Two patients were not evaluable for efficacy: One patient received only one PM00104 infusion in Cycle 1 and had to be withdrawn from the study due to a troponin I increase, which occurred seven days after the first infusion of PM00104 and was considered serious (SAE) and related to PM00104; One patient only received one PM00104 infusion and was withdrawn from the study due to drug-unrelated marantic endocarditis

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 Overall Response Rate (ORR), measured over At baseline and every other cycle (± 1 week) until evidence of PD, up to 2 years.

Overall response rate (ORR) is the primary endpoint. It measures the percentage of patients classified as having either a complete response or a partial response according to RECIST v.1.0. A complete response is defined in the record as disappearance of all lesions. A partial response is defined as a decrease in target lesion size or tumor density meeting the listed RECIST criteria. The record also defines progressive disease and stable disease, which distinguish response categories that do not qualify as complete or partial response.

Response is used as an endpoint because it summarizes whether tumor measurements met predefined categories during follow-up. It is a categorical outcome: each assessed patient is classified according to the response criteria, and the endpoint aggregates the complete and partial response categories. The record specifies assessment at baseline and every other cycle (± 1 week) until evidence of disease progression, up to 2 years.

The registry record identifies the endpoint and its assessment schedule but does not report the number or percentage of patients with complete or partial response. It also notes that two patients were not evaluable for efficacy. The record describes one of those cases: the patient received only one PM00104 infusion in Cycle 1 and withdrew after a serious troponin I increase considered related to PM00104. The reason for the other patient’s non-evaluability is not reported in the registry record. Without the response result and a fully described efficacy population, the endpoint definition alone cannot establish the observed response rate or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In a single-group study, outcomes are described among participants who received the study intervention. The registry record lists Zalypsis (PM00104) as the only arm and records allocation as not applicable. There is no concurrent control group against which to estimate a treatment contrast. A within-group response proportion, if available, would be an observed cohort outcome; it would not answer how the same participants would have fared under a different treatment.

Randomized comparisons help balance measured and unmeasured characteristics between groups in expectation. Without random assignment and a comparator, observed outcomes can reflect the intervention, patient characteristics, disease course, other care, or assessment processes. This is a general limitation of interpreting uncontrolled results, not a claim about what caused any particular outcome in this trial. The registry record’s listed design should therefore guide the scope of conclusions.

How is overall response rate defined?

ORR combines patients classified as having a complete response or a partial response. The record bases those categories on RECIST v.1.0 and specifies assessments at baseline and every other cycle (± 1 week) until evidence of progression, up to 2 years. In general, an endpoint definition makes the classification rule explicit, while an endpoint result reports how many patients met that rule and the relevant analysis denominator. The registry record includes the definition but does not report the response count, percentage, or denominator.

Response criteria depend on how lesions are measured and categorized. The registry text defines complete response as disappearance of all lesions and gives threshold-based definitions for partial response and progression. Stable disease is the category that meets none of the listed complete response, partial response, or progression criteria. General interpretation of a categorical endpoint also depends on consistent assessment and clear rules for patients whose outcome cannot be evaluated. Those details are not fully described in this record.

What does a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under a specified method. For a response proportion, it would help readers judge how precisely the observed proportion is estimated, in addition to seeing the point estimate. It does not address every source of uncertainty: it cannot remove bias from a non-randomized design, unclear endpoint handling, or incomplete outcome reporting. The registry record does not report an ORR estimate or confidence interval, so neither the point estimate nor its precision can be assessed.

What do the sample-size illustrations mean?

The registry record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrations consider detecting a stated fraction of the observed effect. For time-to-event outcomes, the stated quantity is the total number of events; for other outcomes, it is participants per arm. These are planning assumptions, not evidence that the trial used this design or recruited the illustrated numbers.

In particular, the actual study is recorded as single-group, whereas the illustrations assume equal allocation between two arms. That makes them hypothetical planning scenarios rather than a description of the trial’s allocation. Sample-size illustrations are not observed power and do not show the probability that this completed study detected an effect. The record does not report its own sample-size justification or statistical plan. The illustrations should not be used to infer those missing design details.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability exceeds what a chosen statistical model expects. When a model assumes less variability than the data contain, standard errors and uncertainty estimates can be too small, which may make results appear more precise than they are. The appropriate model depends on the outcome and data structure. The registry record does not identify a fitted model or report an analysis for which over-dispersion can be evaluated. This general concept therefore explains a potential modeling concern, not a finding about this trial.

How should safety counts be read?

Safety counts describe participants with reported events in a stated group and are distinct from efficacy response classifications. The registry record gives at-risk and affected counts for serious and other adverse events by cancer group, alongside selected serious adverse event terms and percentages. A count does not convey when an event occurred, how long participants were observed, whether multiple events occurred in one participant, or whether an event was judged related to treatment. Those details are not reported in the registry record. General interpretation requires the event definition, observation period, analysis population, and attribution rules, as well as the count itself.

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("Endometrial Cancer", "Cervical Cancer")
n      <- c(10, 7)
events <- c(0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Endometrial Cancer  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5
ARM  Cervical Cancer  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists ORR as the primary outcome and several secondary outcomes: best tumor response, progression-free survival, progression-free survival rate at 4 months, overall survival, and plasma pharmacokinetic parameters at the first and second infusion. The study summary also describes pharmacogenomic profiling as an aim. When a study evaluates multiple endpoints or repeated comparisons, general statistical practice must consider multiplicity: testing many hypotheses can increase the chance of at least one apparently notable result. The registry record does not report a multiplicity strategy, hierarchy among secondary outcomes, or statistical analysis plan. It is therefore not possible to determine how such issues were handled.

The record identifies two patients as not evaluable for efficacy. It describes one patient’s withdrawal after a serious troponin I increase considered related to PM00104, following only one infusion in Cycle 1. The reason for the other patient’s non-evaluability is not reported in the registry record. The record does not state the ORR analysis denominator, whether non-evaluable participants were excluded or assigned an outcome category, or how other missing assessments were handled.

These details matter because analysis populations and missing-data rules can affect the interpretation of an endpoint. In general, excluding participants with missing outcomes can yield a result that differs from an approach that retains them under a prespecified rule. Such rules should be stated rather than inferred. The record lists no analyses, and it does not report an approach to missing data, analysis populations, interim analyses, or a protocol-level statistical plan. No specific method should be assumed.

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: deep vein thrombosis (16.7%), diarrhoea (14.3%), nausea (14.3%), vomiting (14.3%), anaemia (14.3%).

The serious adverse event summary is separated by cancer group. For Endometrial Cancer, it lists 5 affected participants among 12 at risk; for Cervical Cancer, it lists 3 among 7 at risk. The record lists deaths as 9 for Endometrial Cancer and 5 for Cervical Cancer. These are descriptive figures in the registry record, not a controlled comparison between treatments or groups.

The record identifies Deep vein thrombosis at 16.7%, and Diarrhoea, Nausea, Vomiting, Anaemia, and Abdominal pain at 14.3% each among the listed serious adverse event terms. It does not specify in this summary the event observation period, whether the percentages refer to participants or events, or how repeated events were counted. The terms and percentages should therefore be read as reported safety information without inferring a denominator or a causal relationship.

Seriousness and treatment relatedness are separate concepts. The record explicitly describes the troponin I increase in a patient who withdrew as a serious adverse event considered related to PM00104. It does not provide attribution details for the other listed events. The safety figures alone cannot establish comparative risk or explain the listed deaths.

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

The registry record establishes that this was a Phase II, single-group study of PM00104 (Zalypsis®) in patients with advanced and/or metastatic endometrial or cervical cancer previously treated with one line of systemic chemotherapy. It defines ORR as the primary endpoint and describes its RECIST v.1.0 criteria and assessment schedule. It also provides safety counts by cancer group and lists secondary tumor and pharmacokinetic outcomes.

What the record does not establish is the observed ORR. The response count and percentage are not reported, and the record lists no analyses. The two patients described as not evaluable for efficacy further underscore the need for an explicit denominator and missing-outcome rule, neither of which is reported. Without an effect estimate and an uncertainty measure, readers cannot assess the size or precision of the primary endpoint result.

The single-group design also limits causal interpretation. An outcome observed among participants in this cohort is not a randomized comparison with another treatment. Even if a response estimate were available, it would describe the study group under the recorded assessment process and would not by itself show what would have happened under an alternative treatment.

The safety information should likewise be interpreted descriptively. Group-specific affected counts and listed event terms do not provide a controlled estimate of relative risk. The record does not give enough detail to determine event timing, attribution for most events, or the context of the recorded deaths. The trial status is terminated, but the reason is not reported in the registry record.

Accordingly, the record supports a description of the trial question, design, endpoint definitions, and selected safety figures. It does not support a numerical claim about response, comparative benefit, precision, or why the study ended.

14. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions and outcome reporting are not interchangeable. The registry record defines ORR in terms of complete and partial responses under RECIST v.1.0 and states when assessments were planned. But without the response count, percentage, and analysis denominator, readers cannot evaluate the endpoint estimate. A precise definition is necessary for interpretation, but it does not substitute for the result.

It also highlights the limits of a single-group design. The study can describe outcomes in the cohort receiving PM00104, but there is no listed randomized comparator for estimating a treatment contrast. That distinction remains important regardless of how clearly an endpoint is defined or how many secondary outcomes are listed.

Handling of non-evaluable participants is another practical statistical issue. The record identifies two patients as not evaluable for efficacy, gives a reason for one, and does not report the other reason or the rule used to determine the ORR denominator. A transparent account of analysis populations and missing outcomes helps readers understand exactly what a reported proportion represents.

Finally, the record lists several secondary outcomes and pharmacokinetic measures but no analyses or multiplicity plan. This makes the registry useful for identifying the intended outcome domains while leaving important analytical questions unresolved. These features make the study a useful example of how design, endpoint reporting, missingness, and statistical analysis jointly shape what can be concluded from a trial record.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for statistical interpretation is that the registry record does not report the primary ORR count or percentage, or any analyses. It also does not report an uncertainty estimate for the primary endpoint. The response definition and planned assessment schedule therefore cannot be connected to a reported efficacy result.

The record notes two patients not evaluable for efficacy but does not fully explain their handling. It describes one patient who received only one infusion in Cycle 1 and withdrew following a serious troponin I increase considered related to PM00104. The reason for the other patient’s non-evaluability is not reported in the registry record. The analysis denominator and missing-data approach are also not reported.

The single-group, unmasked design has no listed randomized control group. It can describe cohort outcomes but cannot provide a randomized contrast. The record does not report the reason the study was terminated, its sample-size justification, its statistical analysis plan, interim analyses, or a multiplicity strategy.

Safety interpretation is constrained by limited context. Although affected and at-risk counts are listed by cancer group, the registry record does not provide event timing, duration of observation, full attribution information, or enough detail to interpret the selected serious adverse event percentages. The death counts are listed without a stated cause or relationship to treatment. These limitations are specific to what is recorded and should not be filled in by assumption.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clinical Trial of PM00104 (Zalypsis®) in Patients With Advanced and/or Metastatic Endometrial or Cervical Cancer Previously Treated With One Line of Systemic Chemotherapy — NCT00900562.
• Registry record last updated 2021-10-28; status last verified 2021-07.
• Results first posted 2021-10-28.
• 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

NCT00900562 is a Phase II clinical and pharmacokinetic trial of PM00104 (Zalypsis®) in patients with advanced and/or metastatic endometrial or cervical cancer previously treated with one line of systemic chemotherapy. PharmaMar is listed as sponsor. The record lists 19 enrolled participants, a single-group design, no masking, and a terminated status. The recorded start was 2009-08 and primary completion was 2011-09.

ORR, defined by complete or partial response under RECIST v.1.0, is the primary endpoint. The registry record describes two patients as not evaluable for efficacy but does not report the ORR result or analyses. Listed secondary outcomes include tumor response, progression-free survival, overall survival, and plasma pharmacokinetic measures. Safety figures are presented separately for Endometrial Cancer and Cervical Cancer. The reason for termination and the statistical analysis plan are not reported in the registry record.