Study of Low-Dose Fractionated Radiotherapy in Patients With Locally Advanced Metastatic Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Low-Dose Fractionated Radiotherapy in Patients With Locally Advanced Metastatic Pancreatic Cancer (NCT00761345), a na phase 1 study. The primary outcome is To Determine the Dose Limiting Toxicities.

2. Clinical Question

The clinical question is principally about safety and dose, rather than a comparative estimate of treatment benefit. The study description presents low-dose radiotherapy as a potential way to combine radiation with full dosing of gemcitabine and erlotinib. The record says that participants were enrolled in groups of 3 to 6 with a slightly higher dose of low-dose fractionated radiotherapy and erlotinib. It does not report the dose-escalation rules or a target toxicity rate.

Progression-free survival and overall survival are listed as secondary outcomes. Their observed results and assessment timeframes are not reported in the registry record. Without those results, the record cannot answer how long participants lived without progression or how long they lived overall. The available information supports describing the study objective and design, but not estimating comparative efficacy.

3. Trial Design

This was a Phase I study sponsored by Fox Chase Cancer Center. The registry record lists a single-group model, allocation as NA, and no masking. Enrollment was 27. The record gives a start date of 2008-09, a primary completion date of 2014-07, and a status of COMPLETED.

The treatment combined gemcitabine, erlotinib, and low dose fractionated radiotherapy. Gemcitabine was described at 1000mg/m2 IV on days 1 and 8 of each 21 day cycle. Erlotinib was described as either 100mg PO daily for cohorts 1-3 or 150mg PO daily for cohort 4. Low dose fractionated radiotherapy was given BID on days 1 and 2 and 8 and 9 of each 21 day cycle. The brief description says participants were enrolled in groups of 3 to 6 with a slightly higher dose of radiotherapy and erlotinib. The detailed rules governing those cohorts are not reported in the registry record.

Eligibility was described for people with locally advanced or metastatic pancreatic cancer confined to the abdomen, ECOG performance status of 0-1, 0-1 prior regimens without Gemcitabine or Erlotinib, and no prior radiotherapy. The primary outcome was dose-limiting toxicities, assessed weekly by a physician and nurse and in between as needed until 30 days after treatment termination.

As a single-group study, the design does not separate treatment effects from the course of disease, participant characteristics, or other influences. It can describe outcomes observed among enrolled participants, but it cannot directly estimate how outcomes would have differed under a separate control treatment. The record does not report a randomized allocation, a masking procedure, an analysis plan, or a sample-size justification. Those features should not be inferred from the Phase I label or from the description of cohorts.

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

Analysis population for the primary outcome, as defined in the registry: 27 patients (median age 64years and 15 male) with locally advanced or metastatic pancreatic cancer confined to the abdomen and an ECOG performance status of 0-1 who had received 0-1 prior regimens (without Gemcitabine or Erlotinib) and no prior radiotherapy were eligible.

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: Patients with locally advanced or metastatic pancreatic cancer confined to the abdomen and an ECOG performance status (PS) of 0-1 who had received 0-1 prior regimens (without Gemcitabine or Erlotinib) and no prior radiotherapy were eligible

6. Primary Endpoint

The registry lists the primary outcome as To Determine the Dose Limiting Toxicities, measured over weekly physician and nurse assessment and in between as needed until 30 days after treatment termination.

The primary outcome is titled “To Determine the Dose Limiting Toxicities” and is recorded as a number of participants. In general, a count endpoint describes how many participants experienced an event, rather than how often an event occurred over person-time or how severe a continuous measurement was. The registry record does not provide the observed number for this primary outcome.

The stated assessment process was weekly physician and nurse assessment, with additional assessments in between as needed, until 30 days after treatment termination. This timing indicates the period in which the primary safety outcome was to be assessed. The operational definition of dose-limiting toxicity, the grading system, and the rules for attributing an event to treatment are not reported in the registry record. It is therefore not possible to determine from the record which specific events counted toward this endpoint or how a participant with multiple events was handled.

In general, dose-limiting toxicity is used in early-phase treatment research to assess whether a treatment regimen can be administered at a given dose and to inform dose selection. That general purpose does not establish what dose was considered acceptable in this study. No dose recommendation or dose-limiting toxicity result is reported in the registry record.

Progression-free survival and overall survival are listed as secondary outcomes, but their results and timeframes are not reported in the registry record. They should not be substituted for the missing primary safety result or treated as evidence of a comparative treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study records outcomes among participants receiving a treatment regimen without a concurrent control group. Its summaries can describe what happened in the enrolled group. They do not directly estimate the difference between that regimen and an alternative because outcomes under the alternative are not observed in a comparison group. This study is listed as SINGLE GROUP, with allocation NA and masking NONE. It is therefore not a randomized comparison, and the treatment arms should not be interpreted as like-for-like controls.

The treatment description mentions cohorts with differing doses, but the record does not provide a complete cohort-level outcome analysis or the rules for moving between doses. Cohort descriptions alone do not establish a comparative design. Nor do they reveal how dose selection was made or which participants contributed to each dose-specific estimate.

How should a count endpoint be understood?

The primary outcome is specified as a number of participants with dose-limiting toxicities. In general, a count of affected participants is a direct summary of how many people met an event definition within the assessed group. A rate or proportion can also be useful, but interpretation depends on a clear numerator, denominator, event definition, and follow-up period. Here, the record identifies an assessment period ending 30 days after treatment termination, but does not report the primary outcome count or the event criteria. The result therefore cannot be reconstructed or checked from the registry record.

General statistical practice distinguishes the number of participants with an event from the total number of events. One participant may experience more than one event, so those quantities are not interchangeable. The serious adverse-event summary includes affected-participant counts and listed event terms, but the record does not explain whether term percentages refer to participants, events, or another denominator. They should be read as the registry’s reported percentages rather than reinterpreted as a count of distinct participants for each term.

What would uncertainty measures add?

In general, a confidence interval describes a range of values compatible with a statistical procedure and the observed data, under its assumptions. It helps readers assess the precision of an estimate; a point estimate alone does not show how uncertain it is. The registry record does not report a confidence interval for the primary outcome or the serious-event summaries. The precision of those estimates is therefore not quantified in the recorded results.

For a single-group count, uncertainty would depend on the number of participants, the number meeting the event definition, and the method used to form the interval. Because the primary result and its definition are absent, no such interval can be interpreted for dose-limiting toxicity. No interval should be inferred from the enrollment count alone.

What do the planning assumptions mean?

General power calculations ask how often a statistical procedure would detect a specified effect under stated assumptions if a study were repeated. They are planning tools, not observed trial outcomes. The registry description of planning assumptions refers to 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 an observed effect. For time-to-event outcomes it specifies a total number of events; for other outcomes it specifies participants per arm.

Those assumptions describe a hypothetical planning calculation, not the design that was actually used in this single-group trial. In particular, equal allocation between two arms does not describe the recorded single-group model. Any resulting sample-size illustration must not be read as the trial’s observed power, as a randomized comparison, or as proof that the enrolled group was adequate for the primary endpoint. The registry record does not report the study’s own sample-size justification, target effect, or power calculation.

What analysis details are missing?

The registry lists no analyses. It does not report an analysis population, handling of missing observations, a statistical model, an adjustment strategy, or procedures for multiplicity. General methods for binary outcomes may compare event counts or estimate event probabilities, but choosing among them requires a defined outcome, analysis population, and plan. None should be assumed for this study. Similarly, the record does not say whether every enrolled participant was included in each outcome summary.

Over-dispersion is a general issue when variation in count data exceeds what a chosen model expects; accounting for it can affect uncertainty estimates. The registry record does not report a count model or dispersion assessment, and the primary outcome is described as a number of participants rather than a repeated event count. It would therefore be inappropriate to claim that an over-dispersion adjustment was made or was required. The absence of reported methods limits reproducibility and makes it difficult to assess whether the analyses matched the outcome structure.

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("Radiotherapy and Chemotherapy")
n      <- c(27)
events <- c(27)
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  Radiotherapy and Chemotherapy  27  27  100.0  87.2  100.0  87.5  100.0  87.7  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record names dose-limiting toxicities as the primary outcome and lists progression-free survival and overall survival as secondary outcomes. It does not report a hierarchy of hypotheses, a multiplicity adjustment, or a statistical analysis plan. When several outcomes are tested, general statistical practice considers whether repeated testing affects the interpretation of evidence. No adjustment or testing strategy should be presumed in the absence of a report.

The record lists no analyses and does not report results for the primary or secondary outcomes. It also does not state how missing assessments or incomplete follow-up were handled. Missingness can affect an estimate if the participants with recorded outcomes differ from those without recorded outcomes. Without the number of missing observations, reasons for missingness, and analysis rules, the direction or magnitude of any such effect cannot be assessed.

The eligible population is described, but the analysis populations are not. The record does not say whether outcomes were analyzed for all enrolled participants, only those who began treatment, or another defined group. It also does not report exclusions from analyses or the handling of participants who stopped treatment early. These are not interchangeable questions: enrollment describes who entered the study, while an analysis population describes who contributed to a particular result.

These reporting gaps do not establish that methods were absent from the conduct of the study. They mean that the registry record does not report them, so readers cannot verify how multiplicity, missing data, or analysis populations were handled.

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: pneumonia (14.8%), dehydration (14.8%), ileus (7.4%), dvt (7.4%), diarrhea (7.4%).

The registry lists 15 of 27 participants as affected by serious adverse events and 27 of 27 as affected by other adverse events. These are separate registry summaries; the record does not explain whether the categories overlap, so they should not be added together or treated as mutually exclusive groups. The serious terms listed are Pneumonia and Dehydration, each at 14.8%; Ileus, DVT, and Diarrhea, each at 7.4%; and GI bleed at 3.7%.

These figures describe reported events among the study group. They do not establish that an event was caused by the regimen, and they do not show how event frequency compares with another treatment. The registry record does not report deaths; the death count is not reported in the registry record. It also does not provide event severity grades beyond the serious-event designation, event timing, duration, resolution, or treatment attribution.

In general, an adverse event is a recorded medical occurrence, while seriousness is a classification distinct from whether the treatment caused it. The registry’s serious-event counts should therefore be interpreted as safety reporting, not as causal estimates. The record also does not report how the percentages for individual terms were calculated, so they should be retained as stated rather than converted into counts or assigned a different denominator.

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

The study record documents a Phase I, single-group investigation of low dose fractionated radiotherapy with gemcitabine and erlotinib. The primary objective was to determine dose-limiting toxicities, with assessments described through 30 days after treatment termination. The record also documents adverse-event summaries for the enrolled group. These registry entries describe the study’s purpose and recorded safety information; they do not establish whether the regimen was safe, tolerable, or beneficial.

The primary dose-limiting toxicity result is not reported in the registry record. The listed secondary outcomes, progression-free survival and overall survival, also have no reported results. Therefore, the registry record does not provide outcome estimates from which to judge the primary endpoint or these secondary endpoints. It does not report confidence intervals for these outcomes, so their precision cannot be assessed.

The single-group design has no concurrent control. In general, that design can describe observed events in the treatment group but cannot isolate the effect of treatment from other explanations for those events. The adverse-event counts should not be interpreted as a comparison with standard care, gemcitabine alone, or another regimen. Nor should the treatment description be taken as evidence that the intended doses were delivered to every participant.

The record also does not provide the detailed definition of dose-limiting toxicity, dose-escalation rules, analysis methods, or missing-data procedures. Those omissions limit assessment of how the primary endpoint was measured and analyzed. They do not prove those procedures were not used; they are simply not reported in the registry record.

In short, the available information supports a careful account of the study design, eligibility, treatment schedule, and reported adverse-event counts. It does not support a claim about comparative treatment effect, a definitive dose conclusion, or the degree of uncertainty around the primary outcome. The registry record should be read as an incomplete account of outcomes rather than as evidence that unreported results were favorable, unfavorable, or absent.

14. Why This Trial Matters Statistically

This trial is statistically notable because its central question is an early-phase safety question, while the available registry results do not include the primary outcome. Dose-limiting toxicity is the stated primary objective, and the assessment window is described. Yet without the number meeting the outcome and its operational definition, readers cannot evaluate the main result or its precision.

The single-group design also matters for interpretation. It can provide a description of what was recorded in participants receiving the regimen, but it does not supply a concurrent counterfactual. The adverse-event counts therefore cannot be treated as estimates of excess risk attributable to treatment or as evidence of superiority over another regimen. This is a design limitation for comparative questions, not a reason to disregard the descriptive safety information that is reported.

The record lists progression-free survival and overall survival as secondary outcomes, but gives no results for them. Naming an outcome is not the same as reporting an estimate. Statistical interpretation requires outcome data, a defined analysis population, and methods that explain how estimates and uncertainty were obtained. The record lists no analyses, so those elements cannot be assessed.

Finally, the stated planning assumptions describe an equal-allocation, two-arm illustration, whereas the registered trial model is single-group. That contrast makes it especially important to distinguish planning calculations from the study actually conducted. Sample-size illustrations are not observed power and do not supply missing outcome evidence. The statistical value of this record lies in clarifying the design and reporting gaps as well as the safety counts that are present.

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 is not reported in the registry record, despite dose-limiting toxicities being the stated primary objective. The record does not define dose-limiting toxicity, identify toxicity grades or attribution rules, or provide the count of participants meeting that endpoint. As a result, neither the magnitude nor precision of the primary safety result can be assessed.

The trial has a single-group design with 27 enrolled participants and no concurrent comparator. This limits direct comparisons and makes causal attribution of adverse events difficult. The eligible population was restricted to people with pancreatic cancer confined to the abdomen, ECOG performance status of 0-1, 0-1 prior regimens without Gemcitabine or Erlotinib, and no prior radiotherapy. Results, if reported elsewhere, would not automatically apply to people outside that eligibility description.

The record describes cohort-based dose increases but does not provide the escalation rules, cohort-level enrollment, delivered dose information, or dose-specific outcome results. It also does not report treatment completion, dose interruptions, or the reasons for any changes. These omissions limit interpretation of feasibility and dose selection.

Progression-free survival and overall survival are listed as secondary outcomes without results or assessment timeframes. Analyses, confidence intervals, analysis populations, missing-data handling, and multiplicity procedures are not reported. Serious adverse-event terms and percentages are listed, but definitions of the percentage denominators, event attribution, timing, and resolution are not reported. The registry record therefore supports only a limited descriptive interpretation and does not provide enough statistical detail to evaluate the full outcome analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Low-Dose Fractionated Radiotherapy in Patients With Locally Advanced Metastatic Pancreatic Cancer — NCT00761345.
• Registry record last updated 2017-03-07; status last verified 2017-01.
• Results first posted 2016-03-31.
• 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

The registry record describes a completed Phase I, single-group study sponsored by Fox Chase Cancer Center, with enrollment of 27. It evaluated low dose fractionated radiotherapy with gemcitabine and erlotinib in people with locally advanced or limited metastatic pancreatic cancer. The primary outcome was dose-limiting toxicities, assessed weekly and as needed until 30 days after treatment termination.

The record lists serious adverse events affecting 15 of 27 participants and other adverse events affecting 27 of 27. It names progression-free survival and overall survival as secondary outcomes. The observed primary and secondary outcome results, analysis methods, and confidence intervals are not reported in the registry record. The single-group design does not provide a concurrent treatment comparison, so the recorded safety counts are descriptive rather than comparative.