Phase 1/2a DTA-H19 in Patients With Unresectable Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1/2a DTA-H19 in Patients With Unresectable Pancreatic Cancer (NCT00711997), a na phase 1, phase 2 study. The primary outcome is Maximal Tolerated Dose (MTD) & Dose Limiting Toxicity (DLT) of Intratumoral Injections of BC-819.

2. Clinical Question

3. Trial Design

This was a completed Phase 1/2a study of intratumoral DTA-H19 in patients with unresectable, locally advanced pancreatic cancer. The registry lists 9 participants enrolled, the sponsor as Anchiano Therapeutics Israel Ltd., a start date of 2009-08, and primary completion in 2010-10. The study status is recorded as completed.

The study had a single-group model, no masking, and no allocation. The registry lists two dose cohorts, BC-819 4 mg and BC-819 8 mg. These groups indicate different doses, but they do not create a randomized control comparison. The registry itself cautions that the arms are not a like-for-like control comparison. Any numerical contrast between the dose groups therefore needs to be interpreted as descriptive rather than as a randomized estimate of a dose effect.

The stated aims included assessing safety, tolerability, pharmacokinetics, and preliminary efficacy. The primary objective was to determine the maximum tolerated dose and identify dose-limiting toxicities. Secondary objectives included the adverse-event profile, clinical laboratory analytes, vital signs, pharmacokinetics, tumor response, and possible tumor resectability after 4 intratumoral administrations. Tumor response and tumor resectability are listed as secondary outcomes.

The primary endpoint was assessed at Week 4. Its stated population required receipt of all 4 scheduled treatments and completion of that assessment. The number of participants meeting those requirements is not reported in the registry record. Details about dose-escalation steps, cohort assignment, and the number treated at each dose beyond the listed adverse-event groups 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.

Before assignment: Of the 16 patients screened, 7 were screening failures due to metastatic disease

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants had to receive all 4 scheduled treatments and completed the Week 4 assessment

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 Maximal Tolerated Dose (MTD) & Dose Limiting Toxicity (DLT) of Intratumoral Injections of BC-819, measured over Week 4.

The primary endpoint concerns the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of intratumoral injections, with assessment at Week 4. A DLT is defined in the registry as grade 3 or greater toxicity judged to be at least possibly related to the investigational products. The registry describes a decision rule: if 2 patients in any cohort experience DLTs, the next lower dose is considered the MTD when a lower-dose cohort exists.

In general, a dose-limiting toxicity endpoint is used in early-phase dose-finding research to identify toxicities that constrain dose selection. The severity threshold and relationship assessment specify which events count toward that endpoint; they do not, by themselves, report how many qualifying events occurred. The maximum tolerated dose is a dose-selection conclusion that depends on the prespecified decision rule and the observed dose-limiting toxicities across cohorts.

The registry record names this endpoint and its assessment conditions but does not report an endpoint result, a dose-limiting toxicity count, or an identified maximum tolerated dose. It also does not report how many participants met the requirement to receive all 4 scheduled treatments and complete the Week 4 assessment. Therefore, the endpoint definition can be described, but the result of applying the rule is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a dose-finding endpoint ask?

In general, an early-phase dose-finding endpoint is intended to guide dose selection by relating dose exposure to unacceptable toxicity. The registry defines a dose-limiting toxicity as grade 3 or greater toxicity judged at least possibly related to the investigational products. This definition combines a severity criterion with a judgment about whether the event may be related to treatment. The endpoint is assessed at Week 4, and the stated population includes participants who received all 4 scheduled treatments and completed that assessment.

The registry's decision rule says that if 2 patients in any cohort experience dose-limiting toxicities, the next lower dose is considered the maximum tolerated dose if a lower dose cohort exists. This is a rule for interpreting observed events, not an outcome result. Applying it requires the cohort-specific dose-limiting toxicity counts and the relevant dose ordering. Those result details and the selected maximum tolerated dose are not reported in the registry record.

Why are the dose groups not a control comparison?

In general, randomization helps make groups comparable on average by assigning participants through a chance process. This record identifies no allocation and describes a single-group study; it also states that the arms are not a like-for-like control comparison. The 4 mg and 8 mg cohorts are useful for describing what was recorded at each dose, but a difference between their counts cannot automatically be attributed to dose. The record does not report enough information to evaluate how cohort assignment occurred or whether the groups were comparable in other respects.

Masking is listed as none. In general, masking can reduce the influence of knowledge about treatment assignment on assessments or reporting, depending on who is masked and how outcomes are measured. Since no masking was used, outcome assessments may be more vulnerable to such influences; however, the registry does not describe the assessment process in detail. This is a design consideration, not proof that any reported assessment was biased.

How should counts and uncertainty be read?

The registry reports adverse-event counts for the listed groups rather than inferential estimates. A count describes how many participants were recorded as affected among those listed at risk. It does not show the range of plausible event frequencies in a broader patient population. In general, uncertainty around event estimates is important, especially when groups are small, because a limited set of observations can leave substantial uncertainty about less common outcomes. No confidence intervals for the adverse-event counts are reported in the registry record.

The record lists no statistical analyses. Consequently, there are no reported model-based estimates, tests, confidence intervals, or p-values for the primary endpoint. General statistical methods can describe how such quantities would be used, but no method-specific result can be attributed to this study when it is not reported. The registry does not report a statistical analysis plan, so the planned handling of estimates or inferential procedures is not reported in the registry record.

What does the planning illustration represent?

In general, a sample-size calculation evaluates how many observations a proposed design might need to detect a chosen effect under specified assumptions. This record describes its illustration as planning based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is not the trial's own design. It should not be read as evidence that the actual trial was planned with those assumptions or that the study had a particular probability of detecting an effect.

“Observed power” is not a substitute for uncertainty around an observed estimate. In general, power is a design property calculated from assumptions about an effect, variability, sample size, and a testing procedure. A planning illustration using an observed effect is not a report of the study's prospective design or an inferential result. The registry record does not report a sample-size justification for the study itself. Nor does it report a randomized two-arm comparison matching the equal-allocation assumption in the illustration.

What is not available for interpretation?

The record identifies tumor response and tumor resectability as secondary outcomes, along with safety, laboratory measures, vital signs, and pharmacokinetics as objectives. However, numerical results for those measures are not reported in the registry record. Without outcome values, analysis populations, and uncertainty estimates, readers cannot evaluate the magnitude or precision of those outcomes from the registry record. General statistical principles can explain the purpose of endpoints and estimates, but they cannot supply missing study results.

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("BC-819 4 mg", "BC-819 8 mg")
n      <- c(3, 6)
events <- c(0, 1)
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  BC-819 4 mg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  BC-819 8 mg  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record names a primary endpoint and lists secondary outcomes, including tumor response and tumor resectability. It does not report a statistical analysis plan, a multiplicity adjustment, or how conclusions across multiple outcomes were intended to be controlled. When several outcomes or statistical tests are considered, general statistical practice recognizes that the chance of at least one apparently notable result can increase unless the analysis plan addresses multiplicity. That general concern cannot be converted into a claim about the study's actual testing because analyses are not reported.

The record lists no analyses and does not report inferential results for the primary or secondary outcomes. It therefore provides no information about analysis models, covariate adjustment, confidence intervals, hypothesis tests, or any prespecified hierarchy beyond identifying the primary endpoint and secondary outcomes. These details are not reported in the registry record.

The primary endpoint population is defined as participants who received all 4 scheduled treatments and completed the Week 4 assessment. The number of participants meeting this definition is not reported in the registry record, and the record does not explain how participants who did not meet it were handled. Missing-data procedures, reasons for missing assessments, and the analysis populations for secondary outcomes are not reported in the registry record.

In general, an analysis restricted to participants with complete treatment and assessment information can differ from an analysis that includes everyone enrolled. The direction and size of any difference depend on why information is missing and how those participants are handled. Without counts and methods, the effect of missing information cannot be assessed for this study. No assumptions about missing outcomes or exclusions should be inferred from the stated primary population alone.

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 non-serious adverse event terms

The registry lists serious adverse-event counts by dose group. In the BC-819 4 mg group, 3 participants were at risk and 0 were affected by a serious adverse event. In the BC-819 8 mg group, 6 participants were at risk and 0 were affected. These are the reported counts; they are not a guarantee that serious adverse events are impossible, nor do they establish the frequency that would occur in a larger or different population.

The record lists no serious-event terms, so the types of serious events cannot be described from the registry record. Death counts are not reported in the registry record. For the separate category of other adverse events, the record reports 3 affected among 3 at risk in the 4 mg group and 6 affected among 6 at risk in the 8 mg group. Those counts indicate that each listed participant in each group was recorded as affected in that category, but the event terms and further details are not reported.

In general, adverse-event counts need context about definitions, observation period, event severity, recurrence, and completeness of follow-up. The registry record gives a Week 4 primary endpoint timeframe, but the adverse-event counts should not be assumed to have exactly that observation window unless stated. These figures are descriptive and do not establish a comparative safety effect between the dose cohorts.

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

The posted results establish that the registry lists 9 participants enrolled and provides adverse-event counts for BC-819 4 mg and BC-819 8 mg cohorts. The listed serious adverse-event count is 0 in each cohort, with 3 and 6 participants at risk, respectively. The record also lists other adverse events among all participants shown at risk in each cohort. These counts describe what is recorded for the listed groups; they do not determine the complete safety profile or predict what would occur in other patients.

The primary objective was to determine the maximum tolerated dose and identify dose-limiting toxicities, but the endpoint result itself is not reported in the registry record. The record therefore does not show whether the stated dose-limiting toxicity rule was met or what maximum tolerated dose, if any, was identified. Although tumor response and tumor resectability are listed as secondary outcomes, their results are not reported in the registry record.

The data do not support a randomized comparison between the 4 mg and 8 mg groups. The study has no control arm, and the registry states that the groups are not a like-for-like control comparison. No analyses or inferential estimates are listed. As a result, there is no reported confidence interval or p-value from which to assess precision or statistical evidence for an outcome contrast.

In general, a small early-phase study can provide descriptive information about events observed in its participants, while leaving substantial uncertainty about uncommon events and outcomes in a broader population. This general point does not establish any particular risk or benefit for DTA-H19. The registry results do not establish treatment efficacy, lack of efficacy, or a causal dose effect. They also do not provide enough information to infer the reasons behind missing endpoint results or how participants outside the primary endpoint population were handled.

14. Why This Trial Matters Statistically

This study raises several important statistical questions common to early-phase clinical research. Its primary endpoint is a dose-finding decision based on dose-limiting toxicities, rather than a conventional comparison of treatment outcomes against a randomized control group. The endpoint definition and decision rule are useful to identify what evidence would inform dose selection, while the absence of the endpoint result in the registry record prevents readers from knowing how that rule was applied.

The distinction between dose cohorts and randomized comparison groups matters. The registry lists 4 mg and 8 mg groups, but describes the study as single-group with no allocation and cautions that the groups are not like-for-like controls. That limits causal interpretation of differences between their descriptive counts. It also makes transparent reporting of cohort assignment and outcome details particularly important for understanding how the dose decision was reached.

The safety counts illustrate why denominators and event definitions matter. A count of 0 serious adverse events in a small listed group is not equivalent to evidence that the event cannot occur. The accompanying risk counts help readers understand the observations, but the absence of event terms, mortality counts, and detailed follow-up information limits interpretation. Likewise, counts for other adverse events do not identify event type or severity.

Finally, the registry record lists objectives and outcome names without reporting their numerical results or analyses. Statistical interpretation depends not only on a study question and endpoint definition, but also on transparent results, analysis populations, and uncertainty measures. The gap between a clearly stated clinical question and unavailable endpoint results is itself relevant: readers can identify what the trial set out to assess, but cannot evaluate the primary dose-finding conclusion from the 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 registry record does not report the primary endpoint result, the number of dose-limiting toxicities, or the identified maximum tolerated dose. Although it defines the Week 4 assessment population as participants who received all 4 scheduled treatments and completed the assessment, it does not report how many participants met those conditions. This prevents assessment of the endpoint's observed denominator and of how the stated dose rule was applied.

Enrollment is listed as 9, and adverse-event risk counts are reported for the BC-819 4 mg and BC-819 8 mg groups. Other design details, including how participants were assigned to cohorts and whether cohort-specific follow-up was complete, are not reported in the registry record. The registry names the intervention DTA-H19 and the dose groups BC-819 but does not explain the naming relationship. This leaves a terminology point that readers should not resolve by assumption.

The study had no allocation, no masking, and no randomized control group. The record explicitly cautions that the arms are not a like-for-like control comparison. Accordingly, the adverse-event counts cannot support a randomized estimate of differences between doses. The record also does not list serious-event terms, death counts, numerical tumor response or resectability results, or analyses. The handling of missing data and analysis populations for outcomes beyond the primary endpoint is not reported in the registry record.

In general, early-phase data from limited groups provide restricted information about less common events and the precision of outcome estimates. Here, no confidence intervals or other uncertainty measures for the reported counts are given in the registry record. The sample-size illustration is described as planning rather than as the study's design; the registry does not report the study's own sample-size justification. These limitations constrain interpretation of the posted information without implying that unreported outcomes had any particular result.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 1/2a DTA-H19 in Patients With Unresectable Pancreatic Cancer — NCT00711997.
• Registry record last updated 2019-03-20; status last verified 2019-03.
• Results first posted 2013-12-02.
• 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

NCT00711997 is a completed Phase 1/2a study of intratumoral DTA-H19 in patients with unresectable, locally advanced pancreatic cancer. The registry lists enrollment of 9, a start date of 2009-08, and primary completion in 2010-10. It describes a single-group study with no allocation and no masking, and lists BC-819 4 mg and BC-819 8 mg dose groups.

The primary endpoint concerns maximum tolerated dose and dose-limiting toxicity at Week 4. The registry defines a dose-limiting toxicity and gives a decision rule, but the endpoint result and dose-limiting toxicity counts are not reported in the registry record. Serious adverse-event counts are 0 among 3 at risk in the 4 mg group and 0 among 6 at risk in the 8 mg group; other adverse-event counts are 3 among 3 and 6 among 6, respectively. Death counts are not reported in the registry record. Numerical secondary outcome results and statistical analyses are not reported in the registry record.