Pemetrexed, Gemcitabine, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pemetrexed, Gemcitabine, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer (NCT00310050), a na phase 1 study. The primary outcome is Determine Maximum Tolerated Dose of Pemetrexed When Administered With Concomitant Radiation Therapy.

2. Clinical Question

3. Trial Design

This was a phase I, single-group study of pemetrexed in combination with radiation therapy for locally advanced pancreatic cancer. The registry record gives an enrollment of four participants and a status of terminated. The study started in 2005-10, and its primary completion date is recorded as 2008-05. The reason for termination is not reported in the registry record.

The official title describes a dose-escalating study in which induction gemcitabine/pemetrexed was followed by pemetrexed and concurrent upper abdominal radiation therapy. The brief summary likewise describes the trial as evaluating pemetrexed with radiation. The intervention listing and the arm description identify pemetrexed and radiotherapy, but do not list gemcitabine or provide a detailed treatment schedule. The specific dose levels, escalation rules, and treatment actually received by each participant are not reported in the registry record.

There was one treatment arm, described as pemetrexed in combination with concomitant radiotherapy. Allocation was recorded as not applicable, and masking was recorded as none. These features are consistent with a study focused on dose and tolerability rather than a comparison of outcomes between randomized groups. The registry lists secondary outcome topics including dose-limiting toxicities, patterns of failure, patterns of response, and survival. It records six outcome measures overall, but does not provide results for those outcomes.

The record contains no analysis entries. Most importantly, it states that data were not collected for the primary outcome. Thus, although the study objective and timeframe are listed, the registry record does not supply the outcome observations needed to assess dose escalation or identify a maximum tolerated dose.

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: data were not collected

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 Determine Maximum Tolerated Dose of Pemetrexed When Administered With Concomitant Radiation Therapy, measured over 42 days.

The primary endpoint was to determine the maximum tolerated dose of pemetrexed when administered with concomitant radiation therapy. Its timeframe was 42 days. The endpoint is a dose-finding question: it concerns whether treatment-related toxicity at different dose levels permits identification of a dose judged tolerable under the study’s rules. The registry record does not specify those rules, dose levels, or the definition of a dose-limiting toxicity.

General: In a phase I dose-escalation study, a maximum tolerated dose is used to characterize tolerability within the tested treatment schedule. It is not the same as an endpoint that directly compares clinical benefit between treatment groups. Interpretation depends on the toxicity definition, observation window, escalation method, and participants’ actual exposure. Those details are not reported in the registry record, so the endpoint cannot be reconstructed from the stated objective alone.

The registry record explicitly says that primary outcome data were not collected. It therefore reports neither a dose-level result nor an estimated maximum tolerated dose. The listed 42-day timeframe describes the intended outcome window; it does not establish that participants were observed for that duration or that toxicity findings were available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Design and estimand. The study is recorded as phase I and single group. The stated primary objective is to determine the maximum tolerated dose of pemetrexed with concurrent radiation therapy. An estimand is the precise treatment effect or clinical quantity a study seeks to describe, including the population, treatment, outcome, and timeframe. In this case, the stated target is a dose-tolerance decision over 42 days, rather than a contrast between treatment groups. The registry record does not report a formal estimand, operational decision rule, or detailed analysis plan.

Dose escalation and toxicity. General: Dose-escalation studies examine whether treatment can be given at successive dose levels while tracking defined toxicities. The maximum tolerated dose depends on how toxicity is defined and graded, when it is assessed, which participants count as evaluable, and the rule for moving between doses. A dose-limiting toxicity is generally a prespecified toxicity that affects dose-escalation decisions. The registry lists qualitative dose-limiting toxicities as a secondary outcome and gives a 42-day primary outcome timeframe, but does not report dose levels, grading criteria, escalation decisions, or a dose-limiting toxicity definition. The specific dose-finding method is therefore not reported in the registry record.

Single-group interpretation. General: A single-group study can describe outcomes among participants who received a regimen, but it does not directly estimate how those outcomes differ from a separate control group. Here, allocation is recorded as not applicable, masking as none, and the model as single group. There is no like-for-like control arm. The title and brief summary describe induction chemotherapy followed by concurrent treatment, while the listed intervention and arm description name pemetrexed and radiotherapy. The detailed regimen and participant-level exposures are not reported in the registry record.

Outcome data and precision. The primary outcome record states that data were not collected. The registry record also has zero analysis entries. Accordingly, there is no reported outcome estimate from which to assess statistical precision. General: A confidence interval describes a range of values compatible with data under a specified statistical model and assumptions. It is useful alongside an estimate because it communicates uncertainty, but it cannot be interpreted when the underlying endpoint observations and estimate are absent. No confidence interval or model-based estimate for the primary endpoint is reported in the registry record.

Small-study uncertainty. The enrollment is four participants. General: With very few observations, each participant’s outcome can have substantial influence on a descriptive summary, and uncommon events may not appear even when they are possible. Sparse data also limit the ability to characterize variation across participants or distinguish patterns by dose. These are general consequences of small samples; they do not establish what happened to any individual in this trial. In this record, the missing primary outcome data are an additional limitation beyond the small enrollment.

Safety counts. The registry lists four participants at risk for serious adverse events and zero affected, and four at risk for other adverse events and two affected. It separately records one death. General: Counts of participants with at least one event are different from counts of individual events; one participant can experience multiple events, and the record does not establish whether categories overlap. The registry does not give the serious-event terms or explain the death’s timing, cause, or attribution. It is not possible to infer those details from the counts.

Multiplicity and analysis choices. The record lists six outcome measures and several secondary outcome topics, but gives no analyses. General: When a study examines several outcomes or performs multiple statistical tests, the chance of at least one apparently notable result can increase. A prespecified testing hierarchy or multiplicity adjustment can address aspects of that issue, but neither a testing strategy nor an adjustment is reported in the registry record. The record also does not report a statistical analysis plan, analysis populations, handling of missing observations, or interim analyses. Their existence or absence cannot be inferred from the lack of posted analysis entries.

Planning calculations. General: Sample-size planning illustrations describe hypothetical sample sizes under stated assumptions; they are not observed power and do not replace an analysis of trial outcomes. Any such illustration must be interpreted in light of its assumptions and should not be confused with the number enrolled or with evidence that the study achieved a target level of precision. The registry record does not report an original sample-size justification or trial-specific analysis plan. With no primary outcome data collected, no trial-based estimate of the observed effect is available to answer the dose-finding question.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures, including a primary objective concerning maximum tolerated dose and secondary topics such as qualitative dose-limiting toxicities, patterns of failure, patterns of response, and survival. It records zero analysis entries and reports no results for these outcomes. A testing hierarchy, prespecified primary and secondary analysis procedures, or multiplicity adjustment is not reported in the registry record.

General: Multiplicity becomes relevant when several outcomes, timepoints, groups, or statistical tests are examined. Without a plan for prioritizing hypotheses or accounting for repeated testing, isolated results can be difficult to distinguish from chance findings. Here, no posted outcome analyses are available, so there are no statistical findings for which to assess multiplicity adjustment. The missing information should not be interpreted as evidence that a particular method was or was not used outside the registry record.

The primary outcome is specifically marked as having no data collected. The registry record does not describe missing-data procedures, participant-level outcome availability, reasons for missingness, or whether any participants were considered evaluable for dose-limiting toxicity. It also does not report analysis populations such as an intention-to-treat or per-protocol population. Those details are not reported in the registry record and should not be inferred from the enrollment or safety counts.

The record gives no information about interim analyses or stopping rules. It reports a terminated status, but the reason for termination and any role of interim findings are not reported in the registry record. Thus, neither the handling of missing outcome data nor the decisions that led to termination can be evaluated from the posted information.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry safety entry lists four participants at risk for serious adverse events and zero participants affected. For other adverse events, it lists four at risk and two affected. The record separately lists one death. These are participant counts in the registry’s safety fields; the record does not provide a detailed event narrative.

The serious adverse event terms are not listed. The cause, timing, and relationship of the death to the study treatment are not reported in the registry record. It is therefore not possible to classify the death further or determine whether it overlaps with another safety category. The count of two participants with other adverse events does not identify the event types, severity, duration, or attribution.

General: A count of participants with an event is not necessarily a count of all events, since a participant may have more than one event. Small enrollment also means that a zero count in a particular category is limited information about the range of possible risks. The serious-event count should be read as the record’s reported observation, not as proof that serious events cannot occur.

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

The record establishes that a phase I, single-group study was registered to examine pemetrexed with concomitant radiation therapy in locally advanced pancreatic cancer. It reports enrollment of four participants, a 42-day timeframe for the primary outcome, and a terminated status. It also records selected adverse-event counts. These details describe the trial’s scope and the information entered in the registry.

The central question was whether a maximum tolerated dose could be determined. The registry record says that primary outcome data were not collected. Therefore, it does not identify a maximum tolerated dose or report the dose-limiting toxicities, dose-level decisions, or other primary endpoint results needed to evaluate that objective. The listed secondary outcome topics also lack posted results, and no analysis entries are recorded.

The record does not compare the regimen with a control treatment. It therefore does not provide a randomized estimate of a difference in outcomes or establish a causal treatment effect. The safety entries report zero participants affected by serious adverse events, two affected by other adverse events, and one death; they do not explain the death’s cause or treatment relationship, nor do they characterize the other events.

General: A study objective is not itself a study result. Likewise, a registry entry describing a treatment schedule does not demonstrate that the treatment has a particular benefit or risk. Interpretation requires observed outcomes, a clear account of who was analyzed, and the methods used to define and evaluate those outcomes. For this record, the absent primary outcome data leave the dose-finding question unanswered in the posted results.

The terminated status is a registry status, not an explanation of why the study ended. No reason for termination is reported. The record also does not establish whether the listed interventions fully describe the regimen participants received: the official title describes induction gemcitabine/pemetrexed, while the intervention listing names pemetrexed and radiotherapy. These limits make it important to separate what the record documents from conclusions that would require additional clinical or statistical information.

13. Why This Trial Matters Statistically

This study illustrates why a clearly stated objective and an observed endpoint must be considered separately. The registry identifies a specific phase I goal: determining the maximum tolerated dose of pemetrexed with concurrent radiation therapy. Yet it states that primary outcome data were not collected. Without dose-level observations and the toxicity information used for escalation, the central statistical target cannot be estimated from the registry record.

It also illustrates the limits of interpreting a small, single-group study. Four participants were enrolled, and there was no separate comparator arm. Such a design can be relevant to early dose and tolerability questions, but it cannot provide a randomized comparison of clinical outcomes. General: Small studies can be useful for focused early questions, but their findings are inherently limited in how broadly they characterize variability and uncommon events. In this record, the absence of primary results further prevents an assessment of the intended dose-finding outcome.

The safety entries underscore the importance of distinguishing different kinds of information. A count of zero participants with serious adverse events is not the same as a complete safety profile, particularly when event terms are absent and one death is reported separately without context. The record’s counts should not be expanded into claims about cause, attribution, or risk beyond what is explicitly recorded.

Finally, the difference between the official title’s description of induction gemcitabine/pemetrexed and the listed interventions is a reminder that registry descriptions may not include all details needed to reconstruct treatment exposure. The record does not report the full schedule or dose-escalation method. Taken together, the design, sparse enrollment, terminated status, and missing primary outcome data define a narrow evidentiary record: it documents the intended question and selected safety counts, but does not resolve the dose-finding question.

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.

The most direct limitation is that the registry record states that primary outcome data were not collected. The trial’s stated purpose was to determine the maximum tolerated dose, but no dose-level findings, dose-limiting toxicity results, or estimated maximum tolerated dose are reported. The record also contains zero analysis entries and no posted results for the listed secondary outcome topics.

Enrollment was four participants, and the design was single group. There was no control arm for a comparative treatment estimate. The record does not report a statistical analysis plan, analysis populations, handling of missing observations, interim analyses, or the reason for termination. These details are not reported in the registry record; their absence from the record does not establish what occurred outside it.

The treatment description is incomplete for reconstructing exposure. The official title describes induction gemcitabine/pemetrexed followed by pemetrexed and concurrent upper abdominal radiation therapy, while the intervention list and arm description name pemetrexed and radiotherapy. Specific doses, treatment schedules, radiation details, and escalation rules are not reported in the registry record.

Safety interpretation is limited by the lack of event terms and clinical context. The record does not explain the separately reported death, identify its cause or timing, or provide attribution to treatment. It also does not detail the two participants with other adverse events. The terminated status has no stated explanation, and no reason for termination is reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pemetrexed, Gemcitabine, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer — NCT00310050.
• Registry record last updated 2018-11-30; status last verified 2018-11.
• Results first posted 2018-11-30.
• 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.

18. Record Summary

NCT00310050 is a phase I, single-group study of pemetrexed with concomitant radiation therapy in locally advanced pancreatic cancer. The official title describes induction gemcitabine/pemetrexed followed by pemetrexed and concurrent upper abdominal radiation therapy. The record lists enrollment of four participants, no masking, and a terminated status. It gives a start date of 2005-10 and a primary completion date of 2008-05.

The primary objective was to determine the maximum tolerated dose of pemetrexed with radiation therapy over a 42-day timeframe. The registry record states that primary outcome data were not collected. It lists six outcome measures and zero analysis entries. Safety fields report zero participants with serious adverse events, two with other adverse events, and one death; further event context is not reported in the registry record. The reason for termination is not reported.