This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study of Proton Therapy in Adjuvant Pancreatic Cancer (NCT03885284), a non-randomized phase 1 study. The primary outcome is Incidence of Dose Limiting Toxicites (DLTs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03885284 |
| Phase | Phase 1 |
| Condition | Resected Pancreatic Adenocarcinoma |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 9 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Georgetown University |
| Results posted | Yes |
2. Clinical Question
Population
Patients with resected pancreatic adenocarcinoma were the intended population. The registry summary describes the treatment as adjuvant, meaning it was studied after surgery. Eligibility details beyond the condition and treatment context are not reported in the registry record, so the record does not establish which clinical or demographic characteristics were required for participation.
Intervention
The study combined mFOLFIRINOX with short-course proton beam radiation. The radiation timing varied by dose level: Dose Level 1 scheduled radiation on days 8-12 of cycle 6, while Dose Level 2 scheduled it on days 15-19 of cycle 6. The registry describes the objective as finding a safe schedule integrated with adjuvant mFOLFIRINOX.
Comparator
There was no randomized control group. Both dose levels received mFOLFIRINOX and proton beam radiation; the described difference was the days in cycle 6 on which radiation was given. Because allocation was non-randomized, the groups are not a like-for-like control comparison. The record does not report a separate group receiving mFOLFIRINOX without proton radiation.
Primary question
The primary endpoint was the incidence, expressed as a number, of dose-limiting toxicities over 6 months. The registry says the recommended phase II dose and schedule would be based on the number of these toxicities. Thus, the central question was whether the combined treatment schedule produced dose-limiting toxicity patterns that could guide further study, not whether proton therapy improved survival or recurrence outcomes compared with a control treatment.
3. Trial Design
This was a phase I, parallel, non-randomized study sponsored by Georgetown University. Its registry status is completed. The record lists an enrollment of 9 and gives a start date of 2019-07-15 and a primary completion date of 2022-05-24. These are registry entries, not evidence that every participant completed treatment or follow-up.
The two treatment groups were called Dose Level 1 and Dose Level 2. Both combined mFOLFIRINOX with proton beam radiation. For Dose Level 1, radiation was scheduled on days 8-12 of cycle 6; for Dose Level 2, it was scheduled on days 15-19 of cycle 6. The descriptions identify different radiation timing schedules, but do not specify other treatment differences. Allocation was non-randomized, and masking was absent. The registry lists a parallel model.
The primary outcome was the number of dose-limiting toxicities, assessed over 6 months. The stated purpose was to use the number of these toxicities to determine a recommended phase II dose and schedule for short-course proton radiation integrated within adjuvant mFOLFIRINOX. Recurrence-free survival and overall survival were listed as secondary outcomes.
A phase I dose-and-schedule study has a different inferential purpose from a randomized efficacy trial. Its primary focus is treatment safety and selection of a schedule for further evaluation. With non-randomized allocation, observed differences between the dose levels cannot be interpreted as unbiased causal effects of changing the radiation timing. The registry record does not report the allocation procedure, a formal sample-size justification, or the rules used to choose the recommended phase II schedule.
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
| Stage | Dose Level 1 | Dose Level 2 |
|---|---|---|
| STARTED | 3 | 6 |
| COMPLETED | 2 | 2 |
| NOT COMPLETED | 1 | 4 |
Reasons for not completing this period:
| Reason | Dose Level 1 | Dose Level 2 |
|---|---|---|
| Disease Progression | 1 | 3 |
| Physician Decision | 0 | 1 |
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.
| Characteristic | Unit | Dose Level 1 | Dose Level 2 | Total |
|---|---|---|---|---|
| Participants analysed | 3 | 6 | 9 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 2 | 3 |
| Age, Categorical: >=65 years | Participants | 2 | 4 | 6 |
| Sex: Female, Male: Female | Participants | 1 | 2 | 3 |
| Sex: Female, Male: Male | Participants | 2 | 4 | 6 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 6 | 9 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 3 | 5 | 8 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Incidence of Dose Limiting Toxicites (DLTs), measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Dose limiting Toxicities |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the incidence of dose-limiting toxicities, recorded as a number and assessed over 6 months. A dose-limiting toxicity, often abbreviated DLT, is generally an adverse event that meets protocol-defined criteria for severity, timing, or clinical significance. Those criteria determine which events count toward the endpoint. The detailed DLT definition is not reported in the registry record, so the endpoint cannot be independently reconstructed from the description alone.
In an early-phase study, counting DLTs is a way to assess whether a treatment dose or schedule raises safety concerns that should affect further testing. Here, the registry says the recommended phase II dose and schedule would be based on the number of DLTs observed with short-course proton radiation integrated into adjuvant mFOLFIRINOX. The endpoint therefore addresses treatment tolerability and schedule selection, rather than comparative treatment benefit.
A count needs context to be interpretable. Readers would want to know the number of participants assessed, the observation window, the criteria for an event, how incomplete follow-up was handled, and whether the count refers to participants with at least one DLT or to individual toxicity events. The record gives the 6-month timeframe and identifies the endpoint as a number, but the detailed event definition, analysis population, and observed primary-endpoint results are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study enrolled 9 participants and evaluated two non-randomized schedules that both included mFOLFIRINOX and proton beam radiation. The schedule distinction in the arm descriptions is when radiation was given during cycle 6: days 8-12 for Dose Level 1 and days 15-19 for Dose Level 2. The registry identifies the count of dose-limiting toxicities over 6 months as the primary endpoint and states that it would inform a recommended phase II dose and schedule.
The primary-endpoint result itself is not reported in the registry record. Consequently, the record does not allow readers to assess the observed DLT count for either schedule, determine how the sponsor applied the DLT criteria, or verify which schedule was recommended. Although the study is listed as completed, completion status is not a substitute for an outcome estimate.
The adverse-event figures are reported separately by dose level. For Dose Level 1, the serious-event fields show 0 affected among 3 at risk, and the other-event fields show 3 affected among 3 at risk. For Dose Level 2, the serious-event fields show 1 affected among 6 at risk, and the other-event fields show 6 affected among 6 at risk. The record also reports 2 deaths for each dose level and lists abdominal pain at 16.7% among the top serious terms. These safety entries do not, by themselves, establish that events were caused by treatment or that they met the study's DLT criteria. The event timing, relationship to treatment, and overlap with the primary endpoint are not reported in the registry record.
These groups should not be treated as randomized comparators. Assignment was non-randomized, and the record does not describe how participants entered each dose level. Differences between groups could reflect factors other than radiation timing, including differences in participant characteristics or clinical course. The small enrollment also means that safety counts should be read as descriptive observations from this study, not as precise estimates of risk in a broader population.
Recurrence-free survival and overall survival were listed as secondary outcomes, but outcome estimates for them are not reported in the registry record. The registry lists 5 outcome measures and 0 analyses. Without posted primary and secondary outcome results, uncertainty intervals, and analysis details, conclusions about safety, schedule selection, recurrence, or survival cannot be drawn from the registry entries.
9. Statistical Methods Explained
Clinical trial results require a distinction between the question a study was designed to address and the comparisons that its data can support. This study was a phase I, parallel, non-randomized evaluation of two schedules of proton beam radiation given with mFOLFIRINOX. Its primary question concerned the number of dose-limiting toxicities over 6 months, with the stated goal of using that number to select a recommended phase II dose and schedule. It was not described as a randomized comparison of proton radiation against no proton radiation.
Why randomization matters
In a randomized trial, treatment assignment is determined by a chance process. Randomization can make groups comparable, on average, with respect to measured and unmeasured characteristics, supporting a causal interpretation of differences under appropriate assumptions. In a non-randomized study, assignment may be related to clinical factors, logistics, or investigator decisions. Those factors can also be related to outcomes. As a result, differences between Dose Level 1 and Dose Level 2 cannot be attributed to radiation timing alone from the registry information.
The two arm descriptions specify different radiation days in cycle 6, while both include mFOLFIRINOX and proton beam radiation. This makes the timing schedules clinically relevant to the study question, but it does not make the groups interchangeable. The record does not report how participants were assigned to the dose levels or whether other treatment features differed. That information is important when interpreting any apparent group difference.
What a count endpoint captures
A count endpoint records how many events or affected participants meet a specified definition. For a DLT endpoint, the protocol definition is essential: it determines which toxicities count and the period during which they qualify. General statistical practice may summarize such an endpoint as a count, a proportion, or a rate, depending on the definition and analysis plan. The registry describes this primary endpoint as a number and gives a 6-month timeframe, but does not report the detailed DLT criteria or an observed count.
Counts can be informative for early-phase safety decisions, especially when the decision is whether to continue evaluating a schedule. They are also sensitive to the amount of observation. If participants have different follow-up, a raw count may not convey the same exposure time for everyone. General methods can account for differing observation time when the data and design warrant it, but the registry record does not report whether that issue arose or which method was planned.
Uncertainty and precision
An estimate describes the observed data; a confidence interval describes the range of values reasonably compatible with the data under a statistical model and its assumptions. Intervals are useful because a point estimate alone can make an uncertain result look more definitive than it is. For small studies, estimates of event frequencies can be imprecise, and intervals can be wide. The registry record does not report an interval for the primary endpoint or the safety figures, so their statistical precision cannot be assessed from these entries.
When counts are sparse, normal approximations may not perform well. Exact or other small-sample methods may be considered in general, depending on the estimand and design. For count data with variation greater than a simple model expects, over-dispersion can also matter: a model that assumes too little variability may understate uncertainty. These are general methodological considerations, not methods reported for this trial. The statistical analysis plan and the method used for any posted outcome estimate are not reported in the registry record.
Safety summaries are not the primary endpoint
The registry reports serious adverse-event and other adverse-event fields by dose level. These summaries are distinct from the primary DLT endpoint unless the trial's DLT definition explicitly connects them. A serious adverse event is classified using seriousness criteria, while a DLT is classified according to study-specific dose-limiting rules. The categories can overlap, but they are not automatically equivalent. The record does not report how the DLT endpoint relates to the adverse-event categories or whether the same event could appear in both.
Likewise, a death count is a safety summary, not a measure of treatment effect unless the trial specifies an appropriate causal or comparative analysis. The record gives deaths by dose level but does not report timing, cause, treatment relationship, or an analysis of mortality. Those details are necessary to interpret what the counts mean clinically and statistically.
Planning calculations and observed evidence
Sample-size planning is different from evaluating the evidence collected in a completed study. Planning calculations depend on assumptions about the target effect, significance level, allocation, and statistical model. An illustrative calculation based on an observed effect does not become an observed power estimate, and it does not replace a confidence interval or a direct outcome analysis. The registry record describes planning illustrations using a two-sided significance level of 0.05, equal allocation, and a normal approximation, but does not report the trial's own design justification. The illustrations are planning exercises rather than evidence about the probability that this study detected an effect.
In this study, the registry lists 0 analyses, and the primary outcome result is not reported in the registry record. Therefore, no study-specific p-value, confidence interval, adjusted estimate, or model-based result can be interpreted from the record entries described. The statistical methods used for the outcomes, if any, are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 5 outcome measures, including recurrence-free survival and overall survival as secondary outcomes, alongside the primary DLT endpoint. When a study assesses several outcomes or makes several comparisons, the chance of at least one apparently unusual result can increase if each is tested separately without accounting for multiplicity. General approaches include prespecifying a primary outcome, controlling an overall error rate, or treating secondary analyses as exploratory. The statistical approach to multiplicity is not reported in the registry record.
The registry lists 0 analyses. It does not report a numerical result for the primary endpoint or for the listed secondary outcomes. The methods used to analyze these outcomes, including any model, effect measure, interval estimation, or hypothesis-testing procedure, are not reported in the registry record. The record also does not report whether analyses were planned at interim time points.
Missing-data handling and analysis populations are important for interpreting an outcome. For example, an analysis might include all enrolled participants, only those who started treatment, or only those with evaluable follow-up; those choices can affect the estimate and its interpretation. The registry record does not report the analysis population for the primary or secondary outcomes, how incomplete follow-up was handled, or whether any participants were excluded from outcome analyses. The enrollment figure and adverse-event fields do not establish the completeness of follow-up for each endpoint.
These omissions limit reproducibility and prevent readers from determining whether the reported safety counts align with the planned endpoint definitions. They also mean that absence of a posted result should not be interpreted as evidence of no events or no effect. The primary outcome result, missing-data rules, analysis-population definitions, and multiplicity strategy are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Dose Level 1 | 0 | 3 | 0.0% |
| Dose Level 2 | 1 | 6 | 16.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Dose Level 1 | 2 of 3 |
| Dose Level 2 | 2 of 6 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Dose Level 1 | 3 of 3 |
| Dose Level 2 | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Dose Level 1 | Dose Level 2 |
|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | 0 of 3 | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Dose Level 1 | Dose Level 2 |
|---|---|---|---|
| Peripheral sensory neuropathy | Nervous system disorders | 1 of 3 | 5 of 6 |
| Fatigue | General disorders | 1 of 3 | 3 of 6 |
| Abdominal pain | Gastrointestinal disorders | 2 of 3 | 1 of 6 |
| Diarrhea | Gastrointestinal disorders | 1 of 3 | 1 of 6 |
| Nausea | Gastrointestinal disorders | 2 of 3 | 0 of 6 |
| Neutrophil count decreased | Investigations | 0 of 3 | 2 of 6 |
| Anorexia | Metabolism and nutrition disorders | 0 of 3 | 2 of 6 |
| Pain | General disorders | 0 of 3 | 1 of 6 |
| Alanine aminotransferase increased | Investigations | 1 of 3 | 0 of 6 |
| Alkaline phosphatase increased | Investigations | 1 of 3 | 0 of 6 |
Serious events with the highest arm-level rate: abdominal pain (16.7%).
The registry reports serious adverse-event counts separately for the two dose levels. Dose Level 1 lists 0 affected among 3 at risk; Dose Level 2 lists 1 affected among 6 at risk. For other adverse events, Dose Level 1 lists 3 affected among 3 at risk, and Dose Level 2 lists 6 affected among 6 at risk. The registry also lists 2 deaths in each group and identifies abdominal pain at 16.7% among the top serious terms.
These entries are descriptive safety summaries. The at-risk and affected fields should be read using the registry's categories, not as the DLT outcome: the relationship between those categories and the primary endpoint is not reported in the registry record. Nor do these figures establish that an event was caused by proton radiation or mFOLFIRINOX. The record does not report event timing, duration, attribution, recurrence, or whether an individual could contribute to more than one category. It also does not provide uncertainty intervals for these counts.
Because allocation was non-randomized, group differences in these summaries are not controlled treatment comparisons. The counts should be interpreted as observations within this study, with the limitations of the group sizes and missing event details in mind.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this completed phase I study evaluated short-course proton beam radiation with adjuvant mFOLFIRINOX in patients with resected pancreatic adenocarcinoma. It compared two described radiation schedules within a non-randomized design and identified the number of dose-limiting toxicities over 6 months as the primary endpoint. The stated aim was to use DLT counts to guide a recommended phase II dose and schedule.
The record does not report the observed primary-endpoint result or identify a recommended phase II schedule. It therefore does not establish which schedule had fewer DLTs, how precisely any safety difference was estimated, or whether the study met a particular safety criterion. The adverse-event summaries provide counts by dose level, but they cannot stand in for the missing DLT result because the relationship between those categories is not reported.
The record also does not establish a comparative benefit of proton radiation, a survival advantage, or a reduction in recurrence. Recurrence-free survival and overall survival were listed as secondary outcomes, but their results are not reported in the registry record. With no randomized control group, even posted differences between dose levels would not by themselves isolate a causal effect of radiation timing.
These limitations do not mean that the study has no value. Early-phase investigations can contribute safety and feasibility information that helps shape later research. But a registry entry without outcome estimates, analysis details, or uncertainty measures cannot support conclusions about the magnitude or precision of treatment effects. The appropriate interpretation is restricted to the study design, treatment schedules, endpoint definition as described, and safety counts actually recorded.
13. Why This Trial Matters Statistically
This study illustrates an important distinction in clinical research: a phase I safety question is not the same as an efficacy comparison. The registry's primary endpoint was the number of dose-limiting toxicities over 6 months, and the stated purpose was to guide a recommended phase II dose and schedule. That focus is appropriate to the stated early-phase objective, but it should not be confused with a test of whether proton radiation improves recurrence or survival outcomes.
The design also makes clear why the label “comparison” needs care. Both groups received mFOLFIRINOX and proton beam radiation, and the described schedule difference concerned the days of radiation in cycle 6. Since allocation was non-randomized, the groups cannot be assumed to be comparable. Statistical interpretation must distinguish a descriptive contrast from a causal estimate.
The small enrollment and sparse safety counts underscore the importance of transparent reporting. A DLT definition, analysis population, event attribution, follow-up completeness, and uncertainty estimates are central to interpreting early-phase safety evidence. Without these details and the primary-endpoint result, readers cannot determine how the study's findings informed schedule selection.
The registry record also demonstrates that trial completion and outcome availability are separate matters. A study may be marked completed while analyses and numerical results are not posted. For biostatisticians and clinical researchers, checking the design, estimand, endpoint rules, and analysis reporting is therefore essential before drawing conclusions. In this case, the available information supports a description of the study's question and design, but not an estimate of treatment benefit or a definitive safety ranking of the schedules.
14. 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.
Several limitations specific to this study constrain interpretation. The enrollment was 9, and the dose-level groups were small: Dose Level 1 lists 3 at risk for the adverse-event summaries, while Dose Level 2 lists 6. Safety counts from groups of this size are necessarily limited in how precisely they describe uncommon events or the range of possible event rates. The registry record does not report confidence intervals for these summaries.
Allocation was non-randomized, and the method of assignment is not reported in the registry record. Differences between schedules could therefore reflect participant selection or other factors, rather than radiation timing. Both groups received the combination treatment, so the design does not provide a group without proton radiation for assessing the effect of adding proton therapy.
The detailed DLT criteria and observed primary-endpoint result are not reported in the registry record. This is particularly consequential because DLT count was the stated basis for recommending a phase II dose and schedule. The registry also does not report which analysis population was used, how missing follow-up was handled, the timing and attribution of adverse events or deaths, or the statistical methods used for the outcomes.
Finally, recurrence-free survival and overall survival are listed as secondary outcomes, but their results are not reported in the registry record. The record's completion status does not resolve these reporting gaps. These limitations prevent conclusions about comparative efficacy and make the safety evidence descriptive rather than a precise, controlled estimate.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Proton Therapy in Adjuvant Pancreatic Cancer — NCT03885284.
- Registry record last updated 2024-10-24; status last verified 2023-11.
- Results first posted 2024-10-24.
- 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.
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18. Record Summary
This completed phase I study, sponsored by Georgetown University, enrolled 9 participants with resected pancreatic adenocarcinoma. It evaluated mFOLFIRINOX with proton beam radiation in a non-randomized, parallel design without masking. Dose Level 1 scheduled radiation on days 8-12 of cycle 6; Dose Level 2 scheduled it on days 15-19 of cycle 6.
The primary endpoint was the number of dose-limiting toxicities over 6 months, intended to inform a recommended phase II dose and schedule. Recurrence-free survival and overall survival were listed as secondary outcomes. The registry reports adverse-event counts by dose level but does not report the primary-endpoint result, secondary outcome estimates, or analysis methods. The listed safety counts should therefore be read descriptively, not as randomized comparisons or proof of treatment effect.