Recombinant Measles Virus Vaccine Therapy and Oncolytic Virus Therapy in Treating Patients With Progressive, Recurrent, or Refractory Ovarian Epithelial Cancer or Primary Peritoneal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Recombinant Measles Virus Vaccine Therapy and Oncolytic Virus Therapy in Treating Patients With Progressive, Recurrent, or Refractory Ovarian Epithelial Cancer or Primary Peritoneal Cancer (NCT00408590), a na phase 1 study. The primary outcome is Dose Limiting Toxicity.

2. Clinical Question

3. Trial Design

This was a phase I trial sponsored by Mayo Clinic and listed as completed. The registry records an enrollment of 37, a start date of 2004-04-19, and a primary completion date of 2012-08. Its title describes treatment for progressive, recurrent, or refractory ovarian epithelial cancer or primary peritoneal cancer. The official title specifies intraperitoneal administration of derivatives of a genetically engineered measles-virus strain in patients with recurrent ovarian cancer.

The study was classified as a single-group model, with allocation listed as NA and masking as none. The record therefore does not describe a randomized comparison, and the adverse-event cohorts cannot be interpreted as treatment and control groups. It lists two biological interventions: a carcinoembryonic antigen-expressing measles virus and an oncolytic measles virus encoding the thyroidal sodium iodide symporter. It also lists reverse transcriptase-polymerase chain reaction and laboratory biomarker analysis. The record does not map the interventions to the two adverse-event cohorts.

The stated purpose was to study side effects and the best dose. The brief summary notes that the measles-virus vaccine therapy study closed as of 06/02/2008. The primary outcome is dose-limiting toxicity, with a timeframe of up to 12 months after last treatment. Secondary outcomes include response categories, change in CA-125 from baseline to the last recorded value up to 18 months, and time to progression. Four outcome measures are listed, but the record lists zero analyses. Thus, the design and outcome definitions can be described, while the posted record does not supply analysis results for the primary endpoint or the listed secondary outcomes.

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.

Only the first 6 of 9 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients that received study drug for at least 4 weeks were evaluated for dose limiting toxicities.

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 Dose Limiting Toxicity, measured over up to 12 months after last treatment.

The primary endpoint is the number of participants with dose-limiting toxicities, assessed up to 12 months after last treatment. The record says that patients who received study drug for at least 4 weeks were evaluated for DLTs. It does not provide a clinical definition of which events qualified as a DLT, nor does it report the observed number of participants with DLTs.

In a phase I dose-escalation study, DLT is used to assess whether treatment at a dose is associated with toxicities that limit further escalation. The registry describes a decision process: if one patient experiences a DLT, up to three additional patients are treated at the same dose level. If DLT is observed in only one of six patients treated at a dose level, the next cohort of three patients is treated at the next higher dose level. If two or more patients experience DLT at a dose level, escalation ceases and subsequent patients are treated at a lower dose level. The stated aim is to find the maximum tolerated dose.

This endpoint is a count of participants with DLTs, not a measure of tumor response or long-term benefit. Its interpretation depends on the DLT definition, the assessment process, and the dose-level results. The DLT definition and observed endpoint counts are not reported in the registry record, so the endpoint’s actual trial result cannot be reconstructed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design allow? The registry classifies the study as a single-group trial. In general, a single-group study can describe events observed among treated participants, but without a concurrent randomized comparison it cannot separate treatment-associated changes from other explanations as securely as a randomized controlled design can. The allocation entry is NA and masking is none. The record does not describe a control group, so the cohorts in its safety data should not be used as if they were randomized comparative arms.

How should a count endpoint be understood? The primary outcome is the number of participants with DLTs. For a binary event such as whether a participant experienced a DLT, the count is informative only alongside a clearly defined population, an event definition, and a time window. The registry identifies the population as patients who received study drug for at least 4 weeks and gives a timeframe of up to 12 months after last treatment. It does not report the DLT definition or the observed count. Without those details, the rate and uncertainty around the endpoint cannot be evaluated from the record.

Why does dose escalation use toxicity rules? General explanation: early-phase dose escalation uses observed toxicity to guide decisions about whether to continue at a dose, enroll additional participants at that dose, or move to a different dose. The registry’s stated rules call for up to three additional patients after one DLT, escalation after one DLT among six patients at a dose level, and cessation of escalation if two or more patients experience DLT at a level. This rule description is not the same as a report of what happened. Actual decisions, dose-level enrollment, and the selected maximum tolerated dose are not reported in the registry record.

What does uncertainty mean for event counts? General explanation: a confidence interval describes a range of values compatible with the observed data under a statistical method. It helps distinguish a precise estimate from one with substantial uncertainty. Event counts from small groups can have considerable uncertainty, even when the counts are reported exactly. The registry record does not provide a confidence interval for the DLT endpoint or for the adverse-event cohort counts. No interval can be attributed to the trial from the information posted.

Why does over-dispersion matter? General explanation: over-dispersion occurs when event counts vary more than a statistical model assumes. If a count analysis assumes less variability than is present, standard errors may be too small and uncertainty may appear understated. A model that allows extra variation can be more appropriate for some count outcomes. The primary outcome in this record is a participant count with DLTs, and the record does not report an analysis model or a count distribution. Over-dispersion is therefore a general statistical consideration, not a reported feature or method of this trial.

How should the planning illustrations be read? General explanation: a sample-size calculation estimates the amount of information a future study might need under specified assumptions. It does not describe the number of events actually observed, and it is not observed power. The planning assumptions associated with this record specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the planning approach gives a total number of events using Schoenfeld; for other outcomes, it gives participants per arm. These are planning illustrations, not the trial’s own design justification. The protocol’s sample-size justification is not reported in the registry record.

Can the posted analyses establish an effect? The registry lists four outcome measures and zero analyses. It does not report an estimated treatment effect, uncertainty interval, or hypothesis test for the primary or secondary outcomes. General explanation: a p-value, when reported, describes how compatible data are with a statistical null model; it does not by itself measure clinical importance or prove causation. No p-value for these outcomes is reported in the registry record. The safest statistical reading is to distinguish the study’s stated aims and rules from the results that are actually posted.

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(21, 16)
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  21  0  0.0  0.0  16.1  -0.0  15.5  0.1  15.4
ARM  Cohort 2  16  0  0.0  0.0  20.6  0.0  19.4  0.1  19.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of dose-limiting toxicity and secondary outcomes covering response categories, change in CA-125 from baseline to the last recorded value up to 18 months, and time to progression. It records four outcome measures and zero analyses. Because no analysis results are posted, there is no reported family of hypothesis tests or set of p-values to assess for multiplicity.

General explanation: when several outcomes or several comparisons are tested, the chance of at least one apparently unusual result can increase. Statistical plans may address this through a prespecified hierarchy, an adjustment, or a clear distinction between confirmatory and exploratory outcomes. Such a plan is not reported in the registry record. The record also does not state whether any interim analyses were planned or conducted. Neither multiplicity adjustment nor interim monitoring should be assumed.

The primary endpoint description identifies patients who received study drug for at least 4 weeks as the population evaluated for DLTs. The record does not explain how patients who did not meet that exposure criterion were handled in the primary analysis, whether other analysis populations were defined, or how missing toxicity assessments were addressed. It does not report imputation methods, censoring rules for the secondary outcomes, or procedures for incomplete follow-up. These details are not reported in the registry record.

For CA-125, the outcome is described as change from baseline to the last recorded value up to 18 months. The record does not state how a missing baseline or follow-up value was handled. For response and time to progression, operational definitions and analysis populations are not reported. Consequently, missing-data effects and the analysis population for those outcomes cannot be evaluated from the posted 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nausea (9.5%), small intestinal obstruction (9.5%), vomiting (9.5%), dehydration (9.5%), colonic obstruction (6.2%).

The adverse-event record lists Cohort 1 with 21 at risk and 3 affected for serious events, and Cohort 2 with 16 at risk and 2 affected. These are the counts posted for the cohorts; the record does not explain how the cohort labels correspond to treatment assignment, and the trial is not described as a randomized comparison. The counts therefore describe the registry’s safety summaries rather than a causal contrast between therapies.

The record lists serious-event terms with percentages: Nausea, Small intestinal obstruction, Vomiting, and Dehydration at 9.5% each; Colonic obstruction at 6.2%; and Abdominal distension at 4.8%. The record does not give the denominator or additional method details for these term percentages. They should be read as a selected list of reported terms, not as an exhaustive account or a complete measure of risk.

The other-event counts list all participants at risk in each cohort as affected: 21 of 21 for Cohort 1 and 16 of 16 for Cohort 2. This summary does not establish the seriousness, duration, cause, or outcome of those events. The registry does not report deaths in these cohort summaries. Absence of a death count in this record should not be interpreted as confirmation that no deaths occurred.

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

The record establishes that this was a completed phase I trial intended to study side effects and dose in patients with recurrent or refractory ovarian or primary peritoneal cancer. It identifies DLT as the primary endpoint, describes who was evaluated for that endpoint, and gives a dose-escalation rule intended to guide movement between dose levels. These details explain the study’s purpose and planned decision logic.

The posted information does not establish the observed DLT count, the dose-level pattern of toxicity, or the maximum tolerated dose. It also does not provide analyses for response, CA-125 change, or time to progression. The record therefore does not support an estimate of treatment effect on those outcomes or a conclusion that the therapies did or did not produce a clinical benefit.

The safety summary provides counts for serious events in two cohorts and percentages for selected serious-event terms. Those entries are descriptive. The single-group design, lack of a randomized control comparison, and absence of a mapping between cohorts and virus derivatives limit comparative interpretation. The percentages also lack denominator details in the record, which restricts their interpretation as risks.

General explanation: an observed event in a trial does not by itself show that treatment caused it, and a lack of a posted result is not evidence that the event did not occur. Interpretation depends on complete outcome reporting, a defined analysis population, event definitions, and appropriate treatment of uncertainty. Several of these details are not reported in the registry record.

The appropriate conclusion is bounded: the registry documents the trial’s objectives and some safety summaries, but it does not report the central dose-limiting toxicity result or analyses of the listed secondary outcomes. It cannot establish efficacy, compare the virus derivatives, or identify the dose selected from the information posted.

14. Why This Trial Matters Statistically

This trial matters statistically because phase I studies are designed around safety and dose-finding questions rather than the same outcome questions used in later comparative trials. Here, the primary endpoint is the number of participants with DLTs, and the registry describes explicit escalation and stopping rules. Those rules show how toxicity observations were intended to inform decisions during the study. Without dose-level DLT results, however, readers cannot evaluate how the rules operated or what dose decision followed.

The trial also illustrates the importance of distinguishing a single-group safety description from a treatment comparison. The registry identifies a single-group model, allocation as NA, and masking as none. Cohort-specific adverse-event counts do not create a randomized contrast, especially when the record does not explain which virus derivative each cohort received. Statistical comparisons between those cohorts would not, on their own, isolate an intervention effect.

Outcome completeness matters as much as design. The record names response, CA-125 change, and time to progression, but lists zero analyses. Naming an outcome does not provide its result, precision, or analysis method. This gap makes clear why registry outcome definitions and posted results need to be read separately: an endpoint can be planned and described without a result being available for interpretation.

Finally, the safety entries show why denominators and definitions are essential. Cohort counts are interpretable as descriptive summaries only within the information given, while the term-level percentages have no denominator details in this record. Statistical reporting is most useful when it connects outcomes to populations, time windows, event definitions, and uncertainty. Those links are incomplete here, so conclusions should remain limited to the stated design and posted counts.

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 result needed to assess the trial’s stated dose-finding objective is not reported in the registry record. The DLT count by dose level, the dose levels used, and the maximum tolerated dose are absent. Although the record describes a DLT decision rule, it does not define DLT clinically or report how the rule was applied in practice.

The design is single-group, with allocation listed as NA and masking as none. There is no randomized control comparison described. The adverse-event cohorts cannot be assumed to represent the two viral interventions, because that mapping is not reported. The cohort counts therefore cannot support a direct safety comparison between derivatives.

The safety record gives selected serious-event terms and percentages, but it does not state their denominators or calculation details. It also does not provide detailed event-level information such as timing, duration, outcome, or attribution. The other-event summaries identify affected counts but do not establish severity or clinical course. Death counts are listed as null, which does not supply a reported count.

Although secondary outcomes are named, their results and analyses are absent. The registry does not report analysis methods, uncertainty intervals, missing-data handling, or definitions for response and time to progression. It also does not report a statistical analysis plan, interim analyses, or sample-size justification. The planning assumptions are illustrative and should not be mistaken for the study’s own design rationale. These omissions constrain interpretation of efficacy, precision, and the completeness of follow-up.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Recombinant Measles Virus Vaccine Therapy and Oncolytic Virus Therapy in Treating Patients With Progressive, Recurrent, or Refractory Ovarian Epithelial Cancer or Primary Peritoneal Cancer — NCT00408590.
• Registry record last updated 2024-01-16; status last verified 2024-01.
• Results first posted 2017-10-02.
• 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

NCT00408590 is a completed phase I, single-group trial sponsored by Mayo Clinic. It studied genetically engineered measles-virus therapies in patients with recurrent ovarian cancer or primary peritoneal cancer. The registry lists an enrollment of 37 and identifies dose-limiting toxicity as the primary outcome, evaluated among patients who received study drug for at least 4 weeks and over a timeframe of up to 12 months after last treatment.

The record describes dose-escalation rules and lists response, CA-125 change, and time to progression as secondary outcomes. It also posts adverse-event summaries for Cohort 1 and Cohort 2. However, it lists zero analyses, and the observed primary endpoint result and secondary outcome analyses are not reported in the registry record. The posted information supports a description of the study design and selected safety data, but not a conclusion about the dose selected, comparative safety, or treatment effects.