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 Pralatrexate and Fluorouracil in Treating Patients With Recurrent Solid Tumors (NCT01206465), a na phase 1 study. The primary outcome is Recommended Dose of PDX Given With a Fixed Dose of 5-FU.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01206465 |
| Phase | Phase 1 |
| Condition | Unspecified Adult Solid Tumor, Protocol Specific |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 29 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Nebraska |
| Results posted | Yes |
2. Clinical Question
Population
Adults with recurrent solid tumors were eligible for this phase I trial. The registry lists the condition as “Unspecified Adult Solid Tumor, Protocol Specific.” The record does not report further eligibility details or describe the tumor types represented among participants.
Intervention
Participants received pralatrexate, followed by fluorouracil. Pralatrexate was administered intravenously over 5 minutes on day 1, and fluorouracil was given as a continuous 48-hour intravenous infusion on days 2 and 16. Courses were scheduled every 28 days in the absence of disease progression or unacceptable toxicity.
Comparator
There was no concurrent comparator group. The registry describes a single-group trial and lists allocation as not applicable. The findings therefore do not provide a randomized, like-for-like comparison with another treatment or with no treatment.
Primary question
The primary question was what recommended dose of pralatrexate could be given with a fixed dose of fluorouracil. The registry describes dose-limiting toxicities during the initial course as the basis for determining whether the maximum tolerated dose had been exceeded: that threshold was defined as 2 patients at a given dose level experiencing specified dose-limiting toxicities. The actual recommended dose and the observed primary outcome result are not reported in the registry record.
This is a dose-finding question, not a direct test of whether the combination improves tumor response, delays progression, or is better than another treatment. Response to therapy, grade 3–4 toxicity, pharmacokinetics, genetic polymorphisms, plasma levels, and time to disease progression appear among the secondary outcomes. Their presence does not establish that numerical results for those outcomes are available in the registry record.
3. Trial Design
The registry describes a phase I, single-group clinical trial. It lists no allocation scheme and no masking. In practical terms, the record does not describe random assignment to different groups or blinding of participants or investigators. Because there is no concurrent control group, the trial is not designed as a randomized comparison of the combination against another treatment.
The trial enrolled 29 participants and is marked completed. Its recorded start date is 2010-09-14, and its primary completion date is 2015-02-04. The registry identifies the sponsor as the University of Nebraska. The participant group is described broadly as adults with recurrent solid tumors, with the listed condition “Unspecified Adult Solid Tumor, Protocol Specific.” The specific tumor types and other eligibility details are not reported in the registry record.
The treatment schedule involved pralatrexate by intravenous administration over 5 minutes on day 1, followed by fluorouracil as a continuous 48-hour intravenous infusion on days 2 and 16. Courses were to repeat every 28 days if disease had not progressed and unacceptable toxicity had not occurred. The stated primary outcome concerned the recommended pralatrexate dose alongside a fixed dose of fluorouracil. The primary outcome timeframe is described as the initial course, with “day 1 & 15 of a 4 week schedule.” That wording does not match the treatment schedule’s stated days for fluorouracil, and the registry record does not explain the difference.
The registry lists laboratory biomarker analysis, DNA analysis, high performance liquid chromatography, polymerase chain reaction, nucleic acid sequencing, and a pharmacological study among the interventions or procedures. The record does not give enough detail to infer the exact role of each procedure in dose assignment or outcome analysis. Specific dose levels, the fixed fluorouracil dose, the detailed definition of dose-limiting toxicity, and the statistical plan are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: 29 signed a consent form. Two patients never received any study drug: one became ineligible due to rise in bilirubin; another decided against participating.
Overall Study
| Stage | 75 mg/m^2 | 94 mg/m^2 | 118 mg/m^2 | 148 mg/m^2 | 185 mg/m^2 |
|---|---|---|---|---|---|
| STARTED | 3 | 6 | 6 | 6 | 6 |
| COMPLETED | 3 | 6 | 6 | 6 | 6 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All participants receive pralatrexate IV over 5 minutes on day 1 and fluorouracil IV continuously over 48 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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: Analysis was performed on 27 patients who received study drug; 2 patients did not receive any study drug (1 changed mind after signing consent; 1 no longer eligible due to elevated bilirubin)
| Characteristic | Unit | Treatment (Enzyme Inhibitor Therapy) |
|---|---|---|
| Participants analysed | 27 | |
| Age, Continuous | years | 61 (30 to 80) |
| Sex: Female, Male: Female | Participants | 13 |
| Sex: Female, Male: Male | Participants | 14 |
| Race/Ethnicity, Customized: Race/Ethnicity – Caucasian | Participants | 24 |
| Race/Ethnicity, Customized: Race/Ethnicity – Black, not of hispanic origin | Participants | 1 |
| Race/Ethnicity, Customized: Race/Ethnicity – Hispanic | Participants | 1 |
| Race/Ethnicity, Customized: Race/Ethnicity – Asian | Participants | 1 |
| Region of Enrollment: United States | participants | 27 |
6. Primary Endpoint
The registry lists the primary outcome as Recommended Dose of PDX Given With a Fixed Dose of 5-FU, measured over During the initial course (day 1 & 15 of a 4 week schedule).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | mg per meter square |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is described as the recommended dose of pralatrexate, abbreviated PDX in the registry, when given with a fixed dose of fluorouracil. Its unit is mg per meter square. The timeframe is the initial course, described in the record as day 1 and day 15 of a 4 week schedule. The stated dose-finding rule says that the maximum tolerated dose would have been exceeded when 2 patients entered at a given dose level experienced specified dose-limiting toxicities in the initial cycle.
In general, a dose-finding endpoint is used to guide selection of a dose for further study by balancing treatment exposure against unacceptable toxicity. It is different from an endpoint that measures whether a treatment reduces disease or prolongs time to progression. A recommended dose is a trial-specific decision informed by observations under the protocol; it is not, by itself, evidence of comparative benefit.
The registry record does not report the selected recommended dose, the dose levels tested, the number of participants treated at each dose, or the observed dose-limiting toxicity results. It also does not specify what toxicities met the dose-limiting definition. As a result, the endpoint’s purpose and stated decision rule can be described, but its observed numerical result cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive point is that the registry describes a phase I dose-finding study, while the numerical primary outcome needed to understand its dose recommendation is not reported in the registry record. The study’s stated objective was to identify a recommended pralatrexate dose given with a fixed fluorouracil dose. The posted information does not identify that recommended dose or report the observations used to select it. Consequently, the dose-finding result itself cannot be evaluated from this record.
The design also limits what can be inferred about treatment effects. A single-group trial has no concurrent control arm, and the record lists allocation as not applicable. Any observed response or toxicity in this group would describe experience during the study, not a randomized contrast with another treatment. The registry lists response to therapy and time to disease progression as secondary outcomes, but their numerical results are not reported in the registry record. Even if such outcomes were reported, a single-group design would not establish how they compare with outcomes under another treatment.
The record lists enrollment of 29, while the safety group lists 27 at risk for serious adverse events and 27 at risk for other adverse events. Those denominators should be read as the registry’s stated risk groups for the respective safety summaries; the record does not explain why they differ from enrollment. Serious adverse events affected 10 participants in the listed group, other adverse events affected 27, and 3 deaths are recorded. The record does not state whether the deaths were treatment-related, what caused them, or whether all safety events were judged related to treatment. The listed safety counts therefore describe what was recorded, without establishing causation.
The serious-event terms and percentages are registry-listed summaries. Their interpretation depends on the event definitions, attribution rules, and denominator used for each percentage. Those details are not reported in the registry record. A listed event term should not be read as proof that the treatment caused that event, and a percentage should not be interpreted as a comparative risk without a suitable comparison group and clearly defined denominator.
The registry identifies seven outcome measures and lists secondary measures spanning response, toxicity, pharmacokinetics, genetic polymorphisms, fluorouracil plasma levels, and time to progression. It records no analyses. That does not establish that no analyses were performed; it means that analysis results and methods cannot be assessed from this record. Confidence intervals, hypothesis tests, analysis populations, handling of missing outcomes, and multiplicity procedures are not reported in the registry record.
Overall, the posted information supports a description of the trial’s design, treatment schedule, stated dose-finding rule, and selected safety summaries. It does not support a conclusion about the numerical recommended dose, the precision of the primary estimate, comparative efficacy, or the causal contribution of treatment to reported adverse events or deaths.
9. Statistical Methods Explained
What does a single-group phase I design tell us?
In general, phase I studies are designed to examine treatment administration and safety, and may seek a dose for further study. A single-group design follows participants receiving the study regimen without a concurrent randomized comparison group. It can describe observations among participants treated under the study conditions, but it cannot by itself separate treatment effects from other influences or establish how outcomes would have differed under an alternative treatment.
The registry lists the model as single group, allocation as not applicable, and masking as none. These design features mean that the record does not describe random allocation or blinding. There is no like-for-like control group against which to interpret response, progression, or adverse events. Therefore, the trial’s primary dose-finding aim should be distinguished from comparative questions about benefit or harm.
How is the primary dose-finding endpoint framed?
The primary outcome is the recommended dose of pralatrexate with a fixed dose of fluorouracil, expressed in mg per meter square. The registry’s stated rule refers to specified dose-limiting toxicities during the initial cycle and says the maximum tolerated dose would have been exceeded when 2 patients at a dose level experienced those toxicities. In general, such rules provide a decision framework for dose escalation or selection; they do not alone reveal what dose was ultimately recommended. That requires the observed dose-level and toxicity results, which are not reported in the registry record.
The detailed toxicity criteria, dose levels, allocation of participants across dose levels, and any rules for incomplete observation are not reported. The outcome timeframe also contains a schedule wording difference: the primary endpoint description refers to day 1 and day 15, while the treatment description schedules pralatrexate on day 1 and fluorouracil on days 2 and 16. The registry record does not clarify the discrepancy.
What can an estimate and confidence interval tell a reader?
In general, an estimate gives a numerical summary of an outcome, while a confidence interval communicates the uncertainty around an estimate under the assumptions of the statistical method. A narrower interval generally indicates greater precision, and a wider interval indicates less precision. For a dose-finding outcome, the underlying results and decision process would be needed to understand the stability of a recommended dose. No numerical primary outcome estimate or confidence interval is reported in the registry record, so precision cannot be assessed.
A confidence interval is not a guarantee that the true value lies within its bounds, nor does it describe the probability that a particular treatment will work for an individual. Its interpretation depends on the outcome, analysis, and assumptions used. The statistical plan and any interval estimates for the trial’s outcomes are not reported in the registry record.
Why does the absence of a control group matter?
In general, a randomized comparison helps balance participant characteristics and other influences across groups, supporting interpretation of differences as treatment contrasts. A single-group study does not make that comparison. A response observed during treatment cannot establish what would have occurred without the regimen or under another regimen. Similarly, adverse-event counts describe events recorded among those at risk; without a comparator and clear attribution information, they do not quantify an excess risk caused by treatment.
The registry’s comparison status is not a randomized treatment comparison. Any planning illustration based on an observed effect should be understood as a hypothetical design exercise, not as observed power or proof of a treatment effect. The actual planning assumptions and numerical illustrations are not needed to interpret the primary endpoint, and no numerical sample-size result is reported in the registry record.
Why do dose-finding studies need careful safety interpretation?
In general, toxicity can vary in severity, timing, and relationship to treatment. A dose-limiting toxicity is a protocol-defined event used in a dose decision; it is not necessarily equivalent to every serious adverse event or every event of a particular severity. The registry describes a threshold involving specified dose-limiting toxicities but does not state the detailed definitions. The serious adverse event summary is therefore not interchangeable with the primary dose-limiting toxicity endpoint.
The registry separately lists serious events, other adverse events, and deaths. These categories should be read as distinct summaries rather than combined into a single measure. Their overlap, attribution, and observation periods are not described in the registry record. The serious-event terms have listed percentages, but the corresponding percentage definitions and denominators are not reported there.
What information is needed to reproduce or assess the analysis?
In general, statistical interpretation depends on knowing the analysis population, outcome definitions, observation windows, missing-data rules, and any planned adjustment or testing strategy. For dose finding, the dose assignment and toxicity decision rules are also central. The registry record does not report these details sufficiently to reproduce the primary analysis. It lists no analyses, but that registry entry does not establish whether analyses were conducted outside the record. Without numerical outcome results and methods, the primary estimate, uncertainty, and sensitivity to assumptions cannot be evaluated.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists seven outcome measures, including the recommended-dose primary outcome and secondary outcomes concerning response to therapy, grade 3–4 toxicity, pharmacokinetics, genetic polymorphisms, fluorouracil plasma levels, and time to disease progression. When a study evaluates multiple outcomes or multiple analyses, general statistical practice considers whether repeated testing could increase the chance of a false-positive finding. The statistical plan for handling multiplicity is not reported in the registry record. It is therefore not possible to determine whether any adjustment, hierarchy, or prespecified testing strategy was used.
The record lists no analyses and provides no numerical primary outcome result. It also does not report analysis populations, missing-data counts, reasons for missingness, or methods for handling incomplete observations. These details matter because the group included in an analysis and the treatment of missing outcomes can affect how results are interpreted. Their absence from the registry record does not show that the trial had missing data or that no statistical analyses were conducted.
The enrollment entry is 29, while each listed safety risk group is 27. The registry record does not explain this difference, and it does not specify whether the safety groups reflect exclusions, evaluability, or another rule. No conclusion should be drawn about the reason for the difference. The available record also does not say whether all enrolled participants were included in the primary dose-finding analysis or how participants with incomplete initial-course observation were handled.
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 |
|---|---|---|---|
| Treatment (Enzyme Inhibitor Therapy) | 10 | 27 | 37.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (Enzyme Inhibitor Therapy) | 3 of 27 |
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 |
|---|---|
| Treatment (Enzyme Inhibitor Therapy) | 27 of 27 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment (Enzyme Inhibitor Therapy) |
|---|---|---|
| Thromboembolic Event | Vascular disorders | 4 of 27 |
| Abdominal pain | Gastrointestinal disorders | 3 of 27 |
| Pain | General disorders | 2 of 27 |
| Diarrhea | Gastrointestinal disorders | 2 of 27 |
| gastrointestinal disorders - Other | Gastrointestinal disorders | 1 of 27 |
| Nervous system disorders- Other | Nervous system disorders | 1 of 27 |
| Sepsis | Infections and infestations | 1 of 27 |
| Fracture | Injury, poisoning and procedural complications | 1 of 27 |
| Wound complication | Injury, poisoning and procedural complications | 1 of 27 |
| hypotension | Vascular disorders | 1 of 27 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Enzyme Inhibitor Therapy) |
|---|---|---|
| Mucositis oral | Gastrointestinal disorders | 23 of 27 |
| Anemia | Blood and lymphatic system disorders | 20 of 27 |
| Platelet count decreased | Investigations | 16 of 27 |
| Fatigue | General disorders | 15 of 27 |
| Neutrophil count decreased | Investigations | 13 of 27 |
| Diarrhea | Gastrointestinal disorders | 11 of 27 |
| dehydration | Metabolism and nutrition disorders | 9 of 27 |
| Nausea | Gastrointestinal disorders | 8 of 27 |
| rash, maculo-papular | Skin and subcutaneous tissue disorders | 7 of 27 |
| Hemoglobinuria | Renal and urinary disorders | 5 of 27 |
Serious events with the highest arm-level rate: thromboembolic event (14.8%), abdominal pain (11.1%), pain (7.4%), diarrhea (7.4%), gastrointestinal disorders - other (3.7%).
The safety summary lists 27 participants at risk for serious adverse events, with 10 affected, and 27 at risk for other adverse events, with 27 affected. It also records 3 deaths. These are separate registry summaries; the record does not explain whether the groups or event categories overlap, or how the deaths relate to the event counts. It does not report whether deaths were judged related to treatment or identify their causes.
The registry lists the following serious-event terms and percentages: thromboembolic event, 14.8%; abdominal pain, 11.1%; pain, 7.4%; diarrhea, 7.4%; gastrointestinal disorders - Other, 3.7%; and nervous system disorders- Other, 3.7%. The record does not specify the denominator or calculation method for these percentages. They should therefore be read as listed summaries, not as estimates of a comparative treatment risk.
In general, serious adverse events and dose-limiting toxicities are not interchangeable categories. The detailed definition of dose-limiting toxicity is not reported in the registry record, so the serious-event counts cannot be substituted for the primary dose-finding observations. The safety summaries also do not establish that the regimen caused a reported event.
12. What the Result Does, and Does Not, Mean
The registry record describes a phase I investigation of pralatrexate followed by fluorouracil in adults with recurrent solid tumors. Its primary purpose was dose finding: identify a recommended pralatrexate dose alongside a fixed fluorouracil dose, using a stated toxicity threshold during the initial course. The record also describes the treatment schedule and provides selected safety counts and event terms.
The primary numerical result is not reported in the registry record. The recommended dose, tested dose levels, number of participants at each level, observed dose-limiting toxicities, and the uncertainty around the dose decision are unavailable. Thus, the posted information does not show which dose was selected or how strongly the data supported that choice.
The design does not establish whether the combination improves response or delays disease progression relative to another treatment. There was no concurrent comparator group, and numerical results for the listed response and progression outcomes are not reported in the registry record. Likewise, listed adverse events and deaths describe recorded safety information but do not, without attribution and a comparison, establish that treatment caused those outcomes.
In general, a phase I dose-finding result can inform subsequent research by identifying a regimen and dose for further evaluation. It does not by itself establish clinical benefit or comparative safety. The registry information does not report the detailed protocol, statistical analysis plan, or numerical results needed to judge the dose recommendation or the other listed outcome measures.
The result therefore means that the registry records a completed single-group trial with a dose-finding objective and selected safety summaries. It does not supply enough numerical outcome information to evaluate the primary dose decision, quantify precision, or assess treatment effects. Interpretations should stay within those boundaries.
13. Why This Trial Matters Statistically
This trial is statistically notable because its primary question is a dose-selection question rather than a conventional comparison of outcomes between treatment groups. The registry’s stated threshold links dose finding to specified toxicities in the initial course. Understanding that decision requires detailed information on tested doses, toxicity definitions, participant observations, and the rule used to select a recommendation. Those details and the numerical primary result are not reported in the registry record.
The design also illustrates why the question being asked matters when interpreting a result. A single-group phase I study can describe treatment experience and support a dose-finding process, but it cannot provide a randomized comparison against another regimen. Response, progression, and safety observations from such a design do not by themselves estimate a comparative treatment effect.
The record further distinguishes enrollment from the safety summaries’ risk groups: enrollment is listed as 29, while the risk groups for both serious and other adverse events are 27. Without an explanation of eligibility for those summaries, readers cannot determine why those entries differ. Reporting analysis populations and safety denominators clearly is important for interpreting the scope of outcome counts.
Finally, the record names several secondary outcome areas but does not report their numerical results or analysis methods. This underscores the value of complete outcome reporting: a trial’s stated objectives and measured domains are not enough to evaluate its findings without estimates, uncertainty, definitions, and analysis details. The available record supports a careful description of design and selected safety information, while leaving the primary dose-finding evidence unevaluable.
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 main limitation for interpreting the trial is that the registry record does not report the numerical result for its primary outcome. It identifies recommended dose as the endpoint, but gives no selected dose, dose-level observations, or dose-limiting toxicity results. The threshold refers to specified toxicities, yet their definitions are not included. This prevents assessment of how the decision rule was applied.
The single-group design has no concurrent control group, so it does not support a randomized comparison. The registry also lists no masking. The record does not provide enough participant-level or eligibility information to assess how representative the enrolled group was of adults with recurrent solid tumors more broadly. Specific tumor types and detailed eligibility criteria are not reported in the registry record.
There is a wording difference between the primary outcome timeframe, which refers to day 1 and day 15, and the treatment schedule, which places fluorouracil on days 2 and 16. The record does not clarify this discrepancy. The fixed fluorouracil dose and pralatrexate dose levels are also not reported.
For safety, the listed risk groups contain 27 participants, while enrollment is recorded as 29. The reason is not reported. The record does not explain the serious-event percentage denominators, event attribution, overlap between event categories, or relationship of the deaths to treatment. It also does not provide analysis populations, missing-data methods, a statistical plan, or numerical secondary outcome results. These omissions limit reproducibility and prevent evaluation of precision or the robustness of the conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pralatrexate and Fluorouracil in Treating Patients With Recurrent Solid Tumors — NCT01206465.
- Registry record last updated 2023-12-26; status last verified 2023-12.
- Results first posted 2018-07-16.
- 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
NCT01206465 is a completed phase I, single-group trial sponsored by the University of Nebraska. It enrolled 29 participants with recurrent solid tumors and studied pralatrexate followed by fluorouracil. The schedule describes pralatrexate on day 1 and continuous 48-hour fluorouracil infusions on days 2 and 16, with courses repeated every 28 days in the absence of progression or unacceptable toxicity.
The primary objective was to identify a recommended pralatrexate dose with a fixed fluorouracil dose. The record states a toxicity-based threshold for exceeding the maximum tolerated dose, but does not report the recommended dose or primary outcome result. Safety summaries list 10 participants affected by serious adverse events, 27 affected by other adverse events, and 3 deaths among the stated risk groups. The registry record does not report the detailed analysis methods or numerical results for the listed secondary outcomes.