Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer (NCT00072410), a non-randomized phase 1 study. The primary outcome is Number of Patients With Dose-limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

This was a Phase I, sequential, non-randomized study with no masking. The official title describes a single-dose study of increasing doses of 90Y-hu3S193. The record lists an enrollment of 7 and two cohorts. Cohort 1 received a single intraperitoneal dose containing 10 mg of hu3S193 radiolabeled with 10 millicuries of 90Y, plus 5mCi of 111In-hu3S193 to enable imaging after dosing. Cohort 2 received 10 mg of hu3S193 radiolabeled with 15 millicuries of 90Y, plus 5mCi of 111In-hu3S193 for imaging after dosing.

The study began in 2003-11, reached primary completion in 2005-05, and is listed as completed. Its primary outcome was the number of patients with dose-limiting toxicities up to day 56. The registry record also lists clearance, measured by the half-life of the elimination phase, and the number of patients with human anti-human antibodies after treatment as secondary outcomes.

Because allocation was not randomized, cohort membership does not support a controlled causal comparison. A difference between cohort results, if reported, could reflect factors other than dose; the record does not give details that would allow such factors to be assessed. The study design is suited to describing observations within the cohorts, but the registry record does not report a statistical plan for comparing them. It also does not report a sample-size justification, dose-escalation rules, or interim analyses. The posted information lists no analyses. The primary endpoint results are not reported in the registry record, so the available safety counts cannot be treated as a complete report of the main study question.

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: All patients who entered the study.

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 patients who entered the study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Dose-limiting Toxicities (DLTs), measured over Up to day 56.

The primary endpoint was the number of patients with dose-limiting toxicities (DLTs), with assessment up to day 56. It is a participant-count outcome: the focus is whether a patient met the study’s DLT definition during the stated period, rather than the number of separate events alone. The endpoint population was all patients who entered the study.

The registry record defines DLT using toxicity grade, type, duration, and attribution. Criteria included specified severe non-hematological toxicities, alopecia, prolonged Grade 4 nausea or vomiting, and Grade 4 hematological toxicity with an exception for some short-duration events without specified forms of support. An event also had to be definitely, probably, or possibly related to the investigational agent to count as dose limiting. Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria, Version 2.0.

General context: in early-phase research, a DLT endpoint can help describe treatment tolerability under a prespecified definition and observation window. It is not interchangeable with a count of all adverse events or serious adverse events. The registry record does not report how many participants met the DLT definition, nor does it report a DLT rate. Therefore the posted adverse-event counts cannot establish the primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

These statistical concepts help interpret what a small, sequential Phase I study can and cannot show. The registry record does not report a detailed statistical analysis plan, so general explanations should not be mistaken for methods confirmed to have been used in this trial.

What does a participant count describe?

The primary endpoint is a count of participants meeting a binary definition: each participant either meets the DLT criteria during the assessment period or does not. This endpoint differs from a count of all events. A participant could have more than one adverse event, but the endpoint is defined in terms of whether the participant has a qualifying DLT. The record specifies the grading system, event types and severity thresholds, the duration criterion for some events, the attribution requirement, and the assessment period up to day 56.

General statistical context: counts are easy to interpret, but they do not convey all clinical detail. They do not, by themselves, show how severe an event was beyond the endpoint criteria, when it occurred, how long it lasted, or whether an event that did not meet the DLT definition was still important. Those details require event-level reporting, which is not reported in the registry record.

Why does the design affect interpretation?

In a randomized trial, random assignment is intended to balance measured and unmeasured participant characteristics between treatment groups on average. This study is listed as non-randomized and sequential. The cohorts received different 90Y dose levels, but they are not randomized arms. Consequently, a numerical difference between cohorts would not isolate dose as the cause of the difference. The registry record does not report a planned inferential comparison between the cohorts.

General statistical context: sequential dose cohorts are commonly interpreted through their observed outcomes and the rules that guide dose decisions. The registry record does not report the escalation rules or the statistical decision procedure, so no particular dose-selection method can be attributed to this study. The counts should be read as cohort descriptions, not as a controlled estimate of a dose effect.

What would a confidence interval add?

General statistical context: a confidence interval expresses uncertainty around an estimated quantity, such as a participant-level event probability. A narrow interval indicates greater precision under the method’s assumptions; a wide interval indicates that a range of values remains compatible with the data. With small cohorts, estimates are generally uncertain, and an interval can make that uncertainty more visible than a point estimate alone. The registry record does not report confidence intervals for the primary endpoint or the adverse-event counts.

A confidence interval would not fix limitations in design or reporting. It would quantify sampling uncertainty under an analysis, but would not remove possible differences between sequential cohorts or resolve an endpoint-definition mismatch. Since the DLT count is not reported, a DLT estimate or interval cannot be interpreted from the registry record.

What do the adverse-event categories mean?

The safety listing separates serious adverse events from other adverse events and deaths. These categories are not equivalent to the primary endpoint. A serious adverse event is not automatically a DLT under the definition in this study, and an event in the other-adverse-event category is not automatically excluded from being a DLT. The criteria include specific grades and event types, as well as a relationship requirement. The record does not provide enough event-level detail to classify each reported event against those criteria.

General statistical context: safety summaries often describe the number of participants affected, whereas event listings may also count repeated events. The figures in this record are participant counts, not counts of every individual episode. They should not be added across categories or interpreted as mutually exclusive without information confirming that categories do not overlap. Such overlap details are not reported in the registry record.

How should planning calculations be read?

General statistical context: sample-size calculations can illustrate how many participants per arm might be needed under chosen assumptions to detect a specified effect with a chosen power and significance level. They are planning illustrations, not observed outcomes, and are not observed power. The record states that its planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, it describes total events; for other outcomes, participants per arm.

Those assumptions do not describe this study’s non-randomized, sequential allocation. The registry record does not report that the trial was designed using these calculations, and the available information gives no numerical planning estimates to interpret. A planning illustration cannot replace a prespecified design or make a comparison between the observed cohorts causal.

What analysis is reported?

The registry record lists no analyses. It does not report a statistical test, an adjusted model, a confidence interval, a missing-data method, or a multiplicity procedure. No p-value or inferential conclusion about a cohort difference is reported. General statistical methods such as regression, exact binomial intervals, or adjustment for multiple testing should not be assumed to have been used in the study.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cohort 1", "Cohort 2")
n      <- c(3, 4)
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  Cohort 1  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Cohort 2  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists the primary DLT outcome and secondary outcomes concerning clearance, measured by the half-life of the elimination phase, and human anti-human antibodies after treatment. It lists three outcome measures and no analyses. The results for the primary endpoint and the listed secondary outcomes are not reported in the registry record.

Multiplicity concerns arise when several outcomes or statistical comparisons are examined. General statistical context: if many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis plan addresses that issue. The registry record does not report a multiplicity strategy, a hierarchy of testing, or statistical tests. It is not possible to determine whether adjustment was planned or used.

The record also does not describe missing outcome data, participant exclusions from analyses, or imputation methods. Missing-data handling is important because conclusions can depend on whether participants with incomplete follow-up are omitted, counted in a specified way, or included through a model. These details are not reported in the registry record. The primary endpoint population is described as all patients who entered the study, but the record does not give participant-level completion or endpoint-evaluation information.

Analysis populations beyond that endpoint description are not reported in the registry record. The record does not specify whether safety summaries include everyone who received treatment or another defined population. No assumptions about missingness, exclusions, or analysis populations should be inferred from the cohort counts alone.

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 non-serious adverse event terms

The registry record lists safety counts by cohort. In Cohort 1, 0 of 3 at-risk participants were recorded as affected by a serious adverse event; 2 of 3 were affected by other adverse events; and deaths were 0. In Cohort 2, 0 of 4 at-risk participants were recorded as affected by a serious adverse event; 3 of 4 were affected by other adverse events; and deaths were 0. These are participant counts in the registry’s safety summary.

The serious adverse-event counts should not be read as proof that serious risks are absent. Small cohorts provide limited information about uncommon outcomes, and a zero count does not rule out an event outside the observed participants or observation period. The record does not report confidence intervals or additional follow-up detail for these safety counts.

Nor do these figures give the primary DLT result. The DLT definition includes criteria based on toxicity grade, event type, duration, and relationship to the investigational agent. The registry record does not identify whether the participants with other adverse events met those criteria. It also does not report event-level descriptions or attribution for the other adverse events. The safety counts therefore describe the posted categories but cannot be substituted for a DLT count or interpreted as a treatment-effect comparison.

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

The record establishes that a completed Phase I study enrolled patients with advanced ovarian cancer into sequential cohorts receiving single intraperitoneal doses of 90Y-hu3S193. The cohorts received different 90Y activity levels, with 111In-hu3S193 included for imaging after dosing. The primary question concerned DLTs up to day 56. The posted safety information records no serious adverse events and no deaths in either cohort, alongside other adverse events in both cohorts.

Those observations are descriptive. They do not show that the treatment is effective, and they do not establish that it is free of serious risk. The primary DLT result is not reported in the registry record, and the safety counts do not provide enough detail to determine which participants, if any, met the DLT definition. The record also does not report results for clearance or human anti-human antibodies.

General statistical context: absence of an observed event in a small cohort is compatible with uncertainty about the underlying event probability. Observed counts describe what was recorded among participants in the study; they do not guarantee what would occur in a broader population. Likewise, an observed difference between cohorts would not necessarily reflect a dose effect, because allocation was not randomized and the groups were sequential rather than like-for-like controls.

The registry record does not report a statistical analysis plan, outcome confidence intervals, hypothesis tests, or an efficacy analysis. There is therefore no reported inferential basis for claiming a difference between doses or a broader clinical effect. A sound reading is limited to the study design, endpoint definition, and posted safety counts, with the primary outcome and secondary outcome results noted as not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why design, endpoint definitions, and result reporting need to be considered together. It asks an early-phase safety question using a defined DLT endpoint, yet the registry record does not report the observed DLT count. Without that primary result, the central safety question cannot be answered from the record, even though some adverse-event counts are available.

The sequential, non-randomized design also illustrates an important distinction between cohort description and controlled comparison. Cohorts can document observations at different dose levels, but their outcomes cannot be interpreted as if participants had been randomly assigned to comparable groups. Any apparent variation could have more than one explanation. The record does not report an analysis intended to separate these possibilities.

General statistical context: a count and its uncertainty matter together, especially when cohorts are small. Reporting participant counts can make results accessible, while confidence intervals and transparent methods help readers judge precision. The registry record does not report confidence intervals or analyses for the primary endpoint. Its serious adverse-event counts should therefore be read as observations, not as evidence that the risk is absent.

The case also underscores why safety categories should not be collapsed. Serious adverse events, other adverse events, deaths, and DLTs have different definitions. The DLT definition includes toxicity criteria and an attribution requirement, so counts in another category cannot stand in for it without supporting detail. Clear reporting of the endpoint result, event attribution, follow-up, and analysis population would be needed for a fuller statistical interpretation. Their absence limits what can be concluded from this registry 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 primary limitation for interpretation is that the DLT result is not reported in the registry record, although DLTs are the primary outcome. The adverse-event counts cannot substitute for this endpoint because the definitions differ, and the record does not provide the detail needed to classify individual events against the DLT criteria.

The study is listed as non-randomized, unmasked, and sequential. Cohorts receiving different doses are not equivalent to randomized comparison groups. No controlled estimate of the effect of dose can be derived from the design as described. The registry record does not report cohort-specific baseline characteristics or other information that would help assess differences between groups.

The available safety summaries are limited to counts of participants affected by serious adverse events, other adverse events, and deaths. Event descriptions, attribution details, and confidence intervals are not reported in the registry record. The secondary results for clearance and human anti-human antibodies are not reported either. The record lists no analyses and does not describe missing data, exclusions, or the analysis population for safety outcomes.

The registry record also does not report the statistical analysis plan, dose-escalation rules, sample-size justification, interim analyses, or multiplicity handling. These omissions prevent assessment of whether analyses were prespecified or how decisions were to be made. The listed planning assumptions are not evidence of the trial’s own design, and no numerical planning estimates are available in the record. Together, these reporting and design limitations leave the posted results suitable for narrow description, not broad comparative or efficacy conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Radiolabeled Monoclonal Antibody in Treating Patients With Advanced Ovarian Epithelial Cancer — NCT00072410.
• Registry record last updated 2023-10-04; status last verified 2023-10.
• Results first posted 2021-12-21.
• 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

NCT00072410 is a completed Phase I, non-randomized, unmasked, sequential study sponsored by the Ludwig Institute for Cancer Research. It enrolled 7 patients with ovarian cancer. Cohort 1 received a single intraperitoneal dose of 10 mg of hu3S193 radiolabeled with 10 millicuries of 90Y and 5mCi of 111In-hu3S193. Cohort 2 received 10 mg of hu3S193 radiolabeled with 15 millicuries of 90Y and 5mCi of 111In-hu3S193.

The primary outcome was the number of patients with DLTs up to day 56. The record also lists outcomes for clearance and human anti-human antibodies. It reports serious adverse-event counts of 0 in each cohort and deaths of 0 in each cohort, with other adverse events recorded in both cohorts. The primary endpoint result, secondary outcome results, statistical analyses, and detailed missing-data methods are not reported in the registry record.