Genistein, Gemcitabine, and Erlotinib in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Genistein, Gemcitabine, and Erlotinib in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer (NCT00376948), a na phase 2 study. The primary outcome is Patients Alive.

2. Clinical Question

The stated rationale was to study whether genistein might make tumor cells more sensitive to gemcitabine and erlotinib. That rationale describes the motivation for testing the combination; it is not evidence that the combination improved survival or tumor response. The trial also listed overall objective response, response duration, time to treatment failure, time to progression, grade 3 or higher toxicity, and biomarker activation outcomes. Results for these outcomes are not reported in the registry record.

3. Trial Design

This was a phase II, single-group trial sponsored by Barbara Ann Karmanos Cancer Institute. The registry records the study as completed, with a start in 2005-05 and primary completion in 2010-03. Enrollment was 20. Allocation is listed as not applicable and masking as none. Accordingly, the design does not include a randomized comparison group, and the results cannot provide a treatment-versus-control estimate.

The regimen combined Novasoy® (genistein), gemcitabine, and erlotinib. The arm description specifies Novasoy® 396 mg, including 177 mg of isoflavones, twice daily starting day -7 until day 28; gemcitabine 1000 mg/m2 on days 1, 8, and 15; and erlotinib 150 mg from day 1 until day 28. These are the regimen details recorded for the single group.

The registry names survival at 6 months as the primary outcome, phrased as the number of “Patients Alive.” Secondary outcomes include overall objective response rate, response duration, time to treatment failure, time to progression, grade 3 or higher toxicity evaluation, and pAKT and NF-kappaB activation. The record indicates eight outcome measures, but does not report the numerical result for the primary outcome or results for the listed secondary outcomes.

Although the study is completed, completion status does not supply missing outcome results. The registry record does not report a statistical analysis plan, the number assessed for the primary outcome, or how missing outcome observations were handled. The single-group design is important when interpreting any outcome: it can describe what was observed in the treated group, but without a comparator it cannot isolate the regimen’s effect from other explanations.

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

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 Patients Alive, measured over at 6 months.

The primary outcome is “Patients Alive,” measured as the number of participants alive at 6 months. This is a fixed-time survival outcome: it asks whether each participant was alive at a specified follow-up landmark. The record gives the time point but does not report the number alive, the number whose status was known, or a proportion.

As a general statistical concept, a fixed-time survival measure can be easy to interpret because it focuses on status at a clinically specified time. It does not, by itself, describe when deaths occurred before that point, how long participants survived beyond it, or the timing of follow-up for those whose status is unknown. Time-to-event methods can account for event timing and censoring, but the registry record does not report such an analysis for this primary outcome.

The endpoint is relevant to a trial in advanced cancer because survival is a direct outcome for participants. Still, an outcome name and timeframe do not establish what happened. Without a reported result and clear information about the analysis population and missing status, the primary endpoint cannot be quantified or compared with an external expectation from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a binary primary outcome: whether a participant was alive at 6 months. It describes the result as a number of participants, rather than reporting a time-to-event estimate. The result value is not reported in the registry record. No inferential analysis, confidence interval, or p-value for this endpoint is reported either.

What does a binary endpoint represent?

As a general statistical concept, a binary outcome places each assessed participant into one of two categories, such as alive or not alive at a specified time. A count describes how many participants fall into a category; a proportion additionally relates that count to an analysis denominator. The registry record names a count as the primary measure, but reports neither the count nor the denominator used for analysis. It is therefore not possible to reconstruct a proportion or assess the completeness of endpoint ascertainment.

Binary measures can be straightforward to communicate, but a fixed-time status does not preserve all the timing information in survival data. Participants who die at different times before the landmark are represented by the same status at that landmark. Participants lost to follow-up or otherwise lacking known status require explicit handling. The registry record does not report whether any primary-outcome data were missing or how such data were handled.

How would a time-to-event analysis differ?

In general, a time-to-event analysis uses the time until an event, such as progression or death, and can account for participants whose event time is not observed during follow-up through censoring methods. The registry lists time to treatment failure and time to progression among the secondary outcomes, but it does not report their results or analysis methods. It also does not report a time-to-event analysis for the primary survival outcome. No assumptions about censoring, follow-up duration, or event definitions can be recovered from the outcome titles alone.

A survival curve is a common way to describe the changing probability of remaining event-free over follow-up. A hazard ratio is a comparative time-to-event measure that requires a defined comparison. Neither a survival curve nor a hazard ratio is reported in the registry record. Since this trial has a single group, a treatment-versus-control hazard ratio would not arise from the design as described.

What can the adverse-event counts tell readers?

For the regimen group, the registry records 20 participants at risk for serious adverse events and 14 participants affected. It separately records 20 at risk for other adverse events and 15 affected. These are participant counts; they are not totals of event episodes. The record does not report deaths in the adverse-event entry. Serious adverse event terms are listed with percentages, including nausea at 35.0%, fatigue at 25.0%, pain at 25.0%, neutrophil at 20.0%, vomiting at 20.0%, and diarrhea at 15.0%.

As a general concept, a serious adverse event classification concerns regulatory seriousness, while severity grading describes intensity. The trial’s listed secondary outcome of grade 3 or higher toxicity is a separate measure. Because its results are not reported, the serious-event counts and term percentages cannot be used to infer the grade 3 or higher toxicity result. Nor do these single-group figures estimate excess risk compared with another regimen.

What do the planning illustrations mean?

The planning assumptions describe illustrations based on a stated fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They specify that time-to-event illustrations use a total event count, while other illustrations use participants per arm. These are planning assumptions, not a statistical analysis of this trial. The record does not report the observed primary or secondary effects needed to interpret such illustrations, and a two-arm planning setup does not match the single-group design recorded for this study.

In general, sample-size calculations estimate the amount of information a proposed study might need to detect a specified effect under stated assumptions. They do not measure the probability that an already completed study found a true effect, and they are not observed power. No trial-specific sample-size justification is reported in the registry record. The planning material should therefore not be read as evidence about the result or precision of this trial.

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("Novasoy®, Gemcitabine & Erlotinib")
n      <- c(20)
events <- c(10)
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  Novasoy®, Gemcitabine & Erlotinib  20  10  50.0  27.2  72.8  29.9  70.1  29.8  70.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcomes: survival at 6 months as the primary outcome, along with response, response duration, treatment failure, progression, toxicity, and biomarker outcomes. When many outcomes are assessed, the chance of finding at least one apparently notable result can be affected by multiple testing. As a general statistical practice, investigators may prespecify which outcomes are primary and how additional analyses will be interpreted or adjusted. The registry record names a primary outcome but does not report a multiplicity strategy, a hierarchy among secondary outcomes, or the statistical plan. No adjustment or decision rule should be assumed.

The record does not report the numerical primary outcome or secondary outcome results, nor does it report how many participants contributed data to each outcome. The number with known survival status at 6 months is not reported in the registry record. Missing-data frequency, reasons for missingness, and methods for handling missing observations are also not reported.

Analysis populations are not described in the registry record. It does not say whether the primary analysis included all enrolled participants, only participants who began treatment, or another defined group. The record also does not report an intention-to-treat approach or a per-protocol approach. These details matter because changing who is included can change the estimate and its interpretation. With these methods and results unreported, readers cannot evaluate the impact of missing observations, exclusions, or outcome selection on the findings.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nausea (35.0%), fatigue (25.0%), pain (25.0%), neutrophil (20.0%), vomiting (20.0%).

The registry records serious adverse events for the Novasoy®, gemcitabine, and erlotinib group among 20 participants at risk, with 14 participants affected. For other adverse events, it records 20 at risk and 15 affected. The counts refer to participants with an event, not the total number of event episodes. Deaths are not reported in the adverse-event entry.

The listed serious adverse event terms and percentages are nausea, 35.0%; fatigue, 25.0%; pain, 25.0%; neutrophil, 20.0%; vomiting, 20.0%; and diarrhea, 15.0%. These are the percentages attached to the registry’s listed terms. The record does not provide additional detail in these entries about event timing, recurrence, attribution to a particular intervention, or the analysis used to calculate each percentage.

As a general statistical distinction, seriousness is not the same as severity grade. The record separately names grade 3 or higher toxicity as a secondary outcome, but its result is not reported. These safety figures describe events recorded in the treated group; with no comparator group, they do not quantify a comparative increase or decrease in risk.

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

The registry record establishes that a phase II, single-group study of Novasoy® (genistein), gemcitabine, and erlotinib was completed, with enrollment of 20 participants. It identifies survival at 6 months as the primary outcome and lists several response, progression, toxicity, and biomarker outcomes. It also reports adverse-event counts and selected serious adverse event percentages.

However, the primary survival result is not reported in the registry record. The listed secondary outcomes also lack reported results. The record therefore does not show the number alive at 6 months, the response rate, the time to progression, or the result of the grade 3 or higher toxicity evaluation. It cannot establish the size or precision of a treatment effect on these outcomes.

The design also matters. A single-group trial can document observations among participants receiving a regimen, but it cannot provide a randomized comparison with a control group. Even if an outcome result were available, a difference from an external benchmark would not be equivalent to a concurrent randomized treatment comparison. Other explanations for outcomes would remain possible.

The safety figures are descriptive. They do not show whether adverse events were more or less frequent than they would have been under another treatment, and the serious-event entries cannot replace the unreported severity-based toxicity outcome. The record does not describe enough about event attribution or analysis to make further comparative claims.

Thus, the registry record can inform readers about the study’s design, intended outcomes, regimen, and recorded safety counts. It does not support a conclusion that the regimen did or did not improve survival, response, or disease control. Absence of a reported outcome is not evidence that no outcome occurred; it means the result is not available in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it illustrates the gap between an outcome being named and its result being reported. The record identifies a clear landmark primary outcome, survival at 6 months, but does not report its numerical value or analysis. A reader cannot assess the estimate, its uncertainty, or the completeness of follow-up from the registry entry alone.

Its single-group structure is equally important. A study can describe outcomes in people receiving a regimen, but a concurrent comparator is needed to estimate a treatment contrast directly. With allocation listed as not applicable and masking listed as none, the record does not describe a randomized, blinded comparison. Claims about comparative effectiveness are therefore beyond what this design and the reported results support.

The study also demonstrates why safety outcomes need careful labels. Participant counts for serious and other adverse events are distinct from event episode counts, and serious-event categories do not answer the separate question of grade 3 or higher toxicity. Keeping these measures distinct prevents a descriptive safety entry from being mistaken for a complete severity analysis.

Finally, planning assumptions should be read in the context of the proposed design and available results. The recorded planning framework assumes equal allocation between two arms, whereas this trial is single-group. Without reported observed effects, those illustrations cannot communicate the trial’s result, and they are not observed power. Together, these features make the record useful for understanding trial design and reporting limits, while leaving the principal efficacy outcomes unresolved.

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 interpreting this particular registry entry is that the primary endpoint result is not reported. Although survival at 6 months is specified, the record provides no count, analysis denominator, confidence interval, or description of who had known status at that landmark. The secondary outcome titles likewise lack numerical results. Consequently, neither the magnitude nor precision of the intended efficacy outcomes can be evaluated from the registry record.

The study’s single-group design means there is no like-for-like control comparison. This limits attribution even if outcome data were available. The registry also records no allocation scheme beyond not applicable and no masking. These design details do not reveal how participants were selected, what other care they received, or how outcomes were assessed; those details are not reported in the registry record.

Important analysis details are also absent. The statistical plan, analysis population, handling of missing data, definitions for time-to-event outcomes, and multiplicity approach are not reported. The record does not state how survival status was established or how censoring was treated for time-to-event outcomes. These omissions make it impossible to assess potential sensitivity to analytic choices.

The safety entries report participant counts and selected event-term percentages but do not provide comparative safety estimates. Deaths are not reported in the adverse-event entry, and results for the separate grade 3 or higher toxicity outcome are not available. The planning assumptions describe a two-arm illustration, unlike the single-group design, and no trial-specific sample-size justification is reported. These limitations constrain both efficacy and safety interpretation without implying that unreported outcomes were absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Genistein, Gemcitabine, and Erlotinib in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer — NCT00376948.
• Registry record last updated 2021-03-01; status last verified 2021-02.
• Results first posted 2014-08-26.
• 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

NCT00376948 is a completed phase II, single-group trial sponsored by Barbara Ann Karmanos Cancer Institute. The registry records enrollment of 20 participants with locally advanced or metastatic pancreatic cancer. The regimen comprised Novasoy® (genistein), gemcitabine, and erlotinib. The study started in 2005-05 and reached primary completion in 2010-03.

The primary outcome was the number of participants alive at 6 months. Results for that outcome and the listed secondary outcomes are not reported in the registry record. The adverse-event entry records 14 participants affected by serious events and 15 affected by other events, with 20 at risk in each category. A single-group design does not support a randomized treatment comparison, and the record does not report the statistical plan, analysis populations, or missing-data methods.