Phase 1b Dose Escalation Study of Intravenous JX-594 in Metastatic, Refractory Colorectal Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1b Dose Escalation Study of Intravenous JX-594 in Metastatic, Refractory Colorectal Carcinoma (NCT01380600), a na phase 1 study. The primary outcome is Number of Participants Experiencing Dose-Limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

This was a completed, single-group Phase 1b dose-escalation study of intravenous JX-594 in metastatic, refractory colorectal carcinoma. The registry reports enrollment of 15 participants. The study began on 2010-09-08, and primary completion was recorded as 2012-10-18. Its stated purpose was to evaluate safety and tolerability in patients who were refractory to or intolerant of oxaliplatin, irinotecan, and Erbitux treatments.

Three dose levels are listed: 1e6 pfu/kg bw, 1e7 pfu/kg bw, and 3e7 pfu/kg bw. Cohort descriptions identify 3 participants at the first dose, 3 at the second, and 9 at the third in the adverse-event information. Those cohort counts describe the available safety grouping; the registry record does not explain the dose-escalation decision rules, the timing or basis for moving between doses, or whether additional participants were added for a particular reason.

The study had no randomized control arm, and masking was none. Consequently, comparisons across cohorts are not randomized treatment comparisons. The study is described as a pilot safety study, and the primary outcome was a count of participants with DLTs rather than a comparative efficacy endpoint. The registry also names best overall tumor response based on RECIST and overall survival as secondary outcomes, but the endpoint values for those outcomes are not reported in the registry record.

Further information about the protocol, eligibility criteria beyond the brief summary, statistical analysis plan, and dose-escalation procedures is not reported in the registry record. The design should therefore be understood from the features explicitly recorded: a single group, sequential dose levels, a safety-oriented primary endpoint, and an ITT population defined as participants receiving at least one treatment.

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.

Before assignment: A total of 15 patients were screened for the study. All 15 screened patients (100%) met the eligibility criteria and were successfully enrolled. There were no screen failures or significant events prior to cohort assignment.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The analysis population is the Intent-to-Treat (ITT) population, which includes all patients who received at least one treatment of Pexa-Vec.

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: The baseline analysis population is based on the Intent-to-Treat (ITT) population, which includes all enrolled patients who received at least one treatment of Pexa-Vec

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Experiencing Dose-Limiting Toxicities (DLTs), measured over Up to Day 57 (assessed through 14 days following the 4th and final biweekly JX-594 infusion, an average of 8 weeks)..

The primary endpoint is the number of participants experiencing dose-limiting toxicities. A DLT is defined in the registry as a treatment-related adverse event meeting one of the listed severity or duration criteria: Grade 4 toxicity; Grade 3 hematologic toxicity for > 5 days; or Grade 3 non-hematologic toxicity persisting for > 7 days, with flu-like symptoms that respond to standard therapies excepted. The endpoint is assessed up to Day 57, through 14 days following the 4th and final biweekly infusion; the registry describes this as an average of 8 weeks.

A count of participants with DLTs is useful in dose escalation because it records how many people met the study’s toxicity threshold during the defined assessment period. The registry says this count was used to determine the Maximally-Tolerated Dose and/or Maximum-Feasible Dose. The endpoint is not a measure of tumor response or survival, and it does not include every adverse event: it applies the stated DLT definition and assessment window.

The primary endpoint result itself—the number of participants with DLTs—is not reported in the registry record. Therefore, the record does not show the observed DLT count or the dose determination based on that endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a count: the number of participants who met the DLT definition during the stated assessment period. A count answers how many participants had the event, but its interpretation depends on how many participants were assessed and how the event was defined. The registry identifies the ITT population as all patients who received at least one Pexa-Vec treatment. It does not report the observed DLT count, the number assessed for that endpoint, or a confidence interval around the count.

What does a confidence interval communicate?

In general, a confidence interval describes the uncertainty around an estimate under a specified statistical model and sampling process. For a participant count or event proportion, an interval can help show how much uncertainty remains when the number observed is small. A point estimate alone does not convey that uncertainty. The registry record does not report a confidence interval for the primary endpoint or for the adverse-event counts, so no interval-based precision assessment can be made from the posted results.

Why does the design matter for comparisons?

In general, random allocation helps make treatment groups comparable in expectation, supporting a causal interpretation of differences between them. This study is recorded as single group, with allocation not applicable and masking none. The dose cohorts are therefore not randomized controls. Counts across dose levels can be described, but any apparent difference may reflect cohort composition, exposure, follow-up, or other factors rather than dose alone. The registry record does not report an adjusted comparison between dose cohorts.

What is the role of dose escalation?

In general, dose-escalation studies examine safety across increasing dose levels, often using prespecified rules to guide enrollment and decisions. The registered levels are 1e6 pfu/kg bw, 1e7 pfu/kg bw, and 3e7 pfu/kg bw. The DLT endpoint is explicitly connected to determining the Maximally-Tolerated Dose and/or Maximum-Feasible Dose. However, the particular escalation rules, review process, and dose-selection decision are not reported in the registry record. It would therefore be inappropriate to infer a protocol from the dose levels alone.

How should planning illustrations be interpreted?

In general, sample-size planning estimates the number of participants or events that a future study might need under specified assumptions. The planning assumptions described for this study’s illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a fraction of the observed effect. For time-to-event planning, the stated quantity is total events; for other outcomes, it is participants per arm. These are planning illustrations based on an observed effect, not the trial’s own design and not observed power. The registry record does not report the study’s sample-size justification. No planning value should be interpreted as the number enrolled, a result observed in this study, or evidence that the study had a particular probability of detecting an effect.

What can be inferred from the listed analyses?

The registry lists no analyses. In general, an analysis plan would specify how outcomes are summarized, how missing observations are handled, and whether comparisons or adjustments are intended. Without those details, readers should not assume that a particular model, hypothesis test, interim analysis, or multiplicity adjustment was used. The available primary endpoint is a count, and the adverse-event data are presented as counts by cohort; these descriptions do not establish that inferential testing was performed.

Why does over-dispersion matter in general?

For count outcomes, a simple statistical model may assume that variability follows a particular relationship to the mean. Over-dispersion occurs when the observed variability is greater than that assumption allows. In general, ignoring over-dispersion can make uncertainty appear smaller than it is. This is a general consideration for count data, not a finding about this study: the registry record does not report a count model, dispersion estimate, or model-based analysis.

More broadly, the small cohort counts and absence of a reported primary endpoint result leave limited basis for estimating the frequency or precision of DLTs. The study’s stated safety purpose and endpoint definition remain informative, but the posted information does not supply the result needed to assess that endpoint quantitatively.

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: Pexa-Vec 1 × 10^6 Pfu/kg", "Cohort 2: Pexa-Vec 1 × 10^7 Pfu/kg", "Cohort 3: Pexa-Vec 3 × 10^7 Pfu/kg")
n      <- c(3, 3, 9)
events <- c(0, 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: Pexa-Vec 1 × 10^6 Pfu/kg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Cohort 2: Pexa-Vec 1 × 10^7 Pfu/kg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Cohort 3: Pexa-Vec 3 × 10^7 Pfu/kg  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8

11. Multiplicity, Missing Data and Analysis Populations

The registry names the primary DLT endpoint and lists secondary outcomes of best overall tumor response based on RECIST and overall survival. It reports four outcome measures, but the values for the secondary outcomes are not reported in the registry record. The record lists no analyses. It therefore does not describe a family of statistical tests, an adjustment for multiple comparisons, or a hierarchy for interpreting secondary outcomes. Multiplicity procedures are not reported in the registry record.

In general, multiplicity arises when several outcomes, groups, time points, or statistical tests are examined. If many tests are conducted, the chance of at least one apparently notable result can increase unless the analysis plan accounts for that. This is general statistical context, not a claim about analyses conducted in this study. Since the registry does not list analyses or test results, it is not possible to determine whether multiplicity was addressed or whether any particular result was selected from multiple analyses.

The registry describes the primary endpoint population as ITT, including all patients who received at least one treatment of Pexa-Vec. It does not report how missing DLT assessments were handled, whether all participants completed the specified assessment period, or whether the primary endpoint was available for every participant in that population. The handling of missing data is not reported in the registry record. No assumptions about missing outcomes or imputation methods should be inferred.

The adverse-event groups give counts at risk and affected for each cohort, but the record does not explain whether all participants had the same duration of observation or how incomplete follow-up was handled. Nor does it report an analysis population for the secondary outcomes. These omissions limit assessment of the completeness and comparability of outcome ascertainment.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia necrotising (11.1%), disease progression (11.1%).

The serious adverse-event figures are cohort-level participant counts. For Cohort 1, 3 participants were at risk and 0 were affected; for Cohort 2, 3 were at risk and 0 were affected; for Cohort 3, 9 were at risk and 2 were affected. The registry separately reports other adverse events for 3 of 3 participants in Cohort 1, 3 of 3 in Cohort 2, and 9 of 9 in Cohort 3. Death counts are 2, 1, and 5, respectively. These counts describe what is recorded for each cohort; they do not establish that events or deaths were caused by the intervention.

The top serious adverse-event terms are pneumonia necrotising and disease progression, each reported as 11.1%. The registry does not provide additional detail in these fields about whether the terms refer to participants, episodes, timing, severity beyond their serious classification, or treatment attribution. The counts should not be treated as rates over equal follow-up unless the observation time and method support that interpretation; such information is not reported in the registry record.

Serious adverse events and DLTs are not interchangeable categories. DLTs follow the specific severity, duration, and treatment-relatedness criteria in the primary endpoint definition. The serious adverse-event counts alone do not reveal how many participants met those DLT criteria.

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

The study addresses a safety question in a specific setting: intravenous JX-594 was evaluated in a Phase 1b dose-escalation study involving people with metastatic, refractory colorectal carcinoma. The registry specifies three dose levels, biweekly infusion, and a DLT endpoint intended to inform determination of the Maximally-Tolerated Dose and/or Maximum-Feasible Dose. Those details clarify the study’s aims and the kind of evidence it was designed to collect.

The posted information does not include the primary DLT count, so it does not show how many participants met the endpoint definition. It also does not state which dose, if any, was determined to be the Maximally-Tolerated Dose or Maximum-Feasible Dose. The presence of a defined endpoint is not itself a result. Similarly, the names of secondary outcomes do not establish tumor response or survival findings; those results are not reported in the registry record.

The adverse-event counts describe reported events across the dose cohorts, but they are not evidence from a randomized comparison. The differences in cohort counts cannot establish that one dose caused more or fewer events than another. The death counts are not identified as treatment-related deaths in the registry information. Serious adverse-event terms and percentages also require caution because the record does not describe their timing, attribution, or follow-up context in these fields.

In general, a small single-group dose-escalation study can contribute descriptive safety observations and guide further investigation, but its design does not provide a controlled estimate of comparative benefit or harm. That is a general interpretation of the design, not a claim about a particular clinical effect. The available record supports understanding the planned safety question and the reported cohort counts, while leaving the primary result and key analysis details unresolved.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a well-defined endpoint and an available endpoint result. The registry defines DLT criteria, identifies the assessment window, and explains how the count was intended to inform dose determination. Yet the number of participants who experienced DLTs is not reported in the registry record. For readers assessing evidence, endpoint definitions and endpoint findings serve different roles: a definition explains what would be counted, while the result shows what was observed.

The single-group dose-escalation structure also illustrates why descriptive cohort counts should not be mistaken for comparative estimates. Cohorts at different dose levels are not randomized controls, and their counts do not by themselves isolate the effect of dose. This matters especially when the cohort sizes are small and unequal, as reflected by the reported at-risk counts of 3, 3, and 9. These counts allow the reader to see the scale of the safety groups, but they do not eliminate uncertainty or support causal comparisons.

Finally, the record distinguishes the primary DLT outcome from broader adverse-event reporting. The serious and other adverse-event counts may provide useful descriptive context, but they cannot substitute for the DLT result because the primary endpoint uses its own criteria. The listed tumor-response and survival outcomes likewise cannot be interpreted without their results. Statistically, the key lesson is to keep design, endpoint definition, observed data, and inferential claims separate. The registry provides some of these elements, but not all of them.

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 consequential limitation for interpretation is that the registry record does not report the primary endpoint result. Without the DLT count, readers cannot assess the observed frequency of the event used to inform dose determination. The record also does not identify a selected Maximally-Tolerated Dose or Maximum-Feasible Dose, or explain the dose-escalation decisions.

The design is single group, with no randomized comparator and no masking. Consequently, the dose cohorts cannot serve as like-for-like controls. Their safety counts are descriptive, and the registry does not report adjusted comparisons or confidence intervals. Cohort sizes are limited, and the available fields do not establish whether follow-up or event ascertainment was comparable across cohorts.

The serious adverse-event and death counts are not accompanied in these fields by detailed timing, duration, attribution, or participant-level context. The death counts should not be interpreted as deaths caused by treatment. The serious-event terms and percentages do not replace the primary DLT endpoint, whose criteria are narrower and explicitly defined.

The registry lists best overall tumor response and overall survival as secondary outcomes, but their results are not reported in the registry record. Missing-data handling, statistical analysis methods, multiplicity procedures, interim analyses, and the sample-size justification are also not reported in the registry record. These limitations restrict both quantitative interpretation and assessment of how the results were analyzed. They do not establish that unreported procedures were absent; they mean the registry record does not describe them.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 1b Dose Escalation Study of Intravenous JX-594 in Metastatic, Refractory Colorectal Carcinoma — NCT01380600.
• Registry record last updated 2026-07-08; status last verified 2026-06.
• Results first posted 2026-07-08.
• 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

NCT01380600 is a completed Phase 1b, single-group dose-escalation study of intravenous JX-594 in metastatic, refractory colorectal carcinoma. The registry reports enrollment of 15 and dose levels of 1e6 pfu/kg bw, 1e7 pfu/kg bw, and 3e7 pfu/kg bw. The primary endpoint was the number of participants experiencing DLTs through the specified assessment period, in an ITT population defined as participants receiving at least one treatment.

The registry reports cohort-level serious and other adverse-event counts and deaths, and names best overall tumor response and overall survival as secondary outcomes. It does not report the primary DLT count, the secondary-outcome results, or inferential analyses. The record describes the study’s safety objective and design, but leaves important outcome and analysis details not reported in the registry record.