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 Intensity-Modulated Radiation Therapy, Fluorouracil, and Mitomycin C in Treating Patients With Invasive Anal Cancer (NCT00423293), a na phase 2 study. The primary outcome is Percentage of Subjects With Acute Gastrointestinal (GI) and Genitourinary (GU) Adverse Events (AE) ≥ Grade 2 as Defined by CTCAE v3.0 (Common Terminology Criteria for Adverse Events).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00423293 |
| Phase | Phase 2 |
| Condition | Anal Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 63 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Radiation Therapy Oncology Group |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned patients with invasive anal cancer. The registry lists anal cancer as the condition and describes the primary endpoint population as eligible patients with adverse-event information. The record does not report further eligibility details in the information summarized for this analysis.
Intervention
The treatment combined dose-painted intensity-modulated radiation therapy with fluorouracil, also called 5-FU, and mitomycin C. The stated rationale describes the study as evaluating this combination, with attention to treatment-related acute morbidity. The intervention was delivered as a single-group regimen.
Comparator
There was no separate comparator group. The registry identifies a single-group model and allocation as not applicable. Consequently, the record does not support a direct comparison with another treatment, usual care, or a control regimen.
Primary question
The primary endpoint asked what percentage of participants experienced acute gastrointestinal or genitourinary adverse events of at least grade 2, as assessed with CTCAE v3.0, from treatment start to 90 days. The registry describes how this endpoint was defined but does not report its numeric estimate or confidence interval in the record.
3. Trial Design
This was a phase II, single-group trial sponsored by the Radiation Therapy Oncology Group. The listed regimen combined intensity-modulated radiation therapy with fluorouracil and mitomycin C. The registry describes enrollment of 63 participants, a start in 2006-12, primary completion in 2009-02, and a completed status.
The design has no randomized allocation or separate control arm: allocation is listed as not applicable, and the model is single group. Masking is listed as none. These design features mean that the trial describes outcomes during the studied regimen but does not create a concurrent randomized contrast. Any observed event frequency therefore cannot, by itself, identify what would have occurred under another regimen or without treatment.
The official title identifies the study as an evaluation of dose-painted IMRT in combination with 5-FU and mitomycin C, with reduction of acute morbidity as its stated focus. The brief summary likewise says the phase II trial was studying side effects and how well the combination works. The primary endpoint was an acute toxicity measure; listed secondary outcomes include major radiation-planning deviations, acute and late adverse events, clinical complete response, duration of radiotherapy, survival, disease-free survival, and local-regional failure.
The registry lists 12 outcome measures and 7 analyses, but the statistical plan, allocation procedures beyond the single-group description, and details of any planned interim analyses are not reported in the registry record. The listed enrollment is not a substitute for an endpoint-specific denominator: the adverse-event listing separately gives 52 participants at risk for its event summaries.
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 | 5-FU + Mitomycin + IMRT |
|---|---|
| STARTED | 63 |
| COMPLETED | 52 |
| NOT COMPLETED | 11 |
Reasons for not completing this period:
| Reason | 5-FU + Mitomycin + IMRT |
|---|---|
| Ineligible / No protocol treatment | 11 |
Analysis population for the primary outcome, as defined in the registry: Eligible patients with adverse event information.
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: All eligible patients
| Characteristic | Unit | 5-FU + Mitomycin + IMRT |
|---|---|---|
| Participants analysed | 52 | |
| Age, Continuous | years | 58 (34 to 82) |
| Sex: Female, Male: Female | Participants | 42 |
| Sex: Female, Male: Male | Participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Subjects With Acute Gastrointestinal (GI) and Genitourinary (GU) Adverse Events (AE) ≥ Grade 2 as Defined by CTCAE v3.0 (Common Terminology Criteria for Adverse Events), measured over From the start of treatment to 90 days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the percentage of participants with acute gastrointestinal and genitourinary adverse events of at least grade 2, assessed using CTCAE v3.0. The observation period ran from the start of treatment to 90 days. The record says the highest grade adverse event per subject was counted, so the endpoint represents whether a participant reached the specified severity threshold during the acute period rather than the number of separate episodes.
CTCAE grading organizes adverse events by severity. The registry describes grade 1 as mild, grade 2 as moderate, grade 3 as severe, grade 4 as life-threatening or disabling, and grade 5 as death related to an adverse event. A threshold at grade 2 therefore includes events graded moderate or more severe under this system. The endpoint combines gastrointestinal and genitourinary events, and its stated unit is a percentage of participants.
In general, a percentage endpoint can describe how often a defined event occurred in the population being assessed. A confidence interval communicates uncertainty around the estimate, reflecting that a trial’s observed participants are not the only possible set of participants who might have been studied. The registry identifies a 95% confidence interval as the dispersion measure for this endpoint. However, its numeric percentage and interval are not reported in the registry record. The endpoint definition is available, but the magnitude and precision of the primary result cannot be evaluated from this record alone.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical limitation is that the registry record describes the primary endpoint but does not report its observed percentage or 95% confidence interval. It is therefore possible to explain what was measured, but not to quantify the frequency of acute gastrointestinal or genitourinary events of at least grade 2 from the primary outcome. The record’s endpoint definition specifies the observation window, grading system, and rule of counting each participant’s highest grade; these details clarify the intended measure but do not supply the result.
The study enrolled 63 participants, while the adverse-event summary lists 52 at risk. These figures refer to different record entries and should not be treated as interchangeable. The primary population is described as eligible patients with adverse-event information, but the record does not give a numeric primary endpoint estimate or a complete explanation of the relationship between enrollment and endpoint-specific information. The reason for the difference is not reported in the registry record.
There is no randomized comparator. This matters because an event percentage within a single treatment group is a description of observed outcomes, not an estimate of the difference between treatments. Without a concurrent comparison group, the record cannot separate effects associated with the regimen from other influences on outcomes. No causal claim about comparative benefit or harm follows from the design alone.
The adverse-event listing reports 6 participants with serious adverse events among 52 at risk. It also reports 52 participants affected in the separate other-adverse-event category among 52 at risk. The registry lists serious-event terms with percentages, including dehydration at 3.8% and anemia at 1.9%. These summaries should be read according to their stated categories; they do not replace the missing primary endpoint result. A null entry for deaths is not evidence that no deaths occurred, because the death count is not reported in the registry record.
In general, confidence intervals are useful for distinguishing a relatively precise estimate from one that remains uncertain. A confidence interval does not eliminate the limitations of an uncontrolled design, and it cannot establish causation. Since the primary interval itself is not reported, the precision of the primary endpoint is also not assessable from the record. No adjusted comparison, treatment effect estimate, or primary endpoint p-value is reported in the registry record.
9. Statistical Methods Explained
The trial’s reported design and endpoint define what can be interpreted statistically. The record identifies a phase II single-group study, with no masking and no separate randomized comparator. The primary outcome is a participant-level percentage for acute gastrointestinal and genitourinary adverse events of at least grade 2. The following explanations describe general statistical principles; they do not imply that particular analyses were performed unless the registry record says so.
What does a single-group design estimate?
In general, a single-group study can describe the outcomes observed among participants who received the studied regimen. For a binary endpoint such as whether a participant experienced an event, the basic descriptive quantity is the proportion of assessed participants with that event. The primary endpoint is framed as a percentage, but the record does not include its numerical value. The adverse-event summary has separate counts for serious and other events; those summaries should not be substituted for the primary gastrointestinal and genitourinary endpoint.
A single-group result does not estimate a randomized difference between treatments. Even if an event proportion were available, a comparison with an external expectation or historical group would require assumptions about whether the groups were comparable and whether outcome definitions and follow-up were alike. Those assumptions and any such comparison are not reported in the registry record. The absence of a control arm also means the trial cannot directly show how outcomes would differ under an alternative regimen.
What does the confidence interval add?
In general, a confidence interval gives a range of values compatible with the observed data under the interval’s statistical assumptions. Its width conveys precision: a narrower interval indicates less sampling uncertainty than a wider interval, while neither width nor location resolves systematic bias or creates a control group. The primary endpoint specifies a 95% confidence interval as its dispersion measure, but the actual interval is not reported in the registry record. The interval’s method is also not reported, so its construction cannot be assessed.
For a percentage, interval methods need to account for the fact that the quantity is bounded and depends on the number of participants with and without the event. Different methods can behave differently, particularly when event counts are sparse or the percentage is near a boundary. This is general statistical context, not a statement about which interval method the trial used.
Why does the event definition matter?
The endpoint applies a threshold: adverse events are counted when their grade is at least 2, using CTCAE v3.0, and the highest grade per participant is counted. In general, a thresholded binary endpoint can simplify interpretation by distinguishing participants who did or did not reach a specified severity level. It also discards detail about lower-grade events, the number of repeated episodes, and the timing of events within the observation window. Counting only the highest grade avoids counting a participant multiple times in the primary percentage, but it does not describe the full course of toxicity.
The registry defines acute toxicities as those occurring within 90 days of treatment start and gives the primary timeframe as treatment start to 90 days. The record does not describe how events with incomplete follow-up were handled, whether ascertainment was uniform, or how events that could not be graded were treated. Those details affect interpretation of a participant-level percentage and are not reported in the registry record.
How should adverse-event categories be read?
The adverse-event information lists a serious-event summary and a separate other-event summary. The serious-event listing reports 6 affected participants among 52 at risk; the other-event listing reports 52 affected among 52 at risk. These are registry categories and should not be interpreted as a breakdown of the primary endpoint. Seriousness and severity are also distinct concepts in general: seriousness concerns regulatory or clinical consequences, whereas CTCAE grade describes severity. The record’s primary outcome specifically uses CTCAE grades, while the safety listing labels events as serious or other.
The listed serious-event terms have accompanying percentages. These term-level figures provide a descriptive listing, not a comparative risk estimate. The registry does not report a control group, adjusted analysis, or test comparing these terms across treatments. Nor does the record explain whether participants could contribute to more than one serious-event term. No additional counts or totals should be inferred from the percentages.
What do planning calculations mean?
In general, sample-size calculations are conditional planning exercises. They ask what enrollment might be needed under specified assumptions about the effect to detect, significance level, allocation, and statistical method. They are not evidence that a study achieved a particular probability of detecting an effect after the fact, and they do not change the precision of an observed result. Any planning illustrations associated with this trial are not the trial’s original design justification, according to the stated assumptions. The trial’s own sample-size justification is not reported in the registry record.
The stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The record distinguishes participant-per-arm planning for non-time-to-event outcomes from total event planning for time-to-event outcomes. These are assumptions for illustration, not features of the single-group trial design; no randomized two-arm comparison is reported. The registry does not report the calculated planning values in the information available for this analysis, so no sample-size conclusion can be drawn from them.
Overall, the record supports explanation of the endpoint and design but not reconstruction of the primary analysis. The statistical analysis plan, exact confidence-interval method, handling of missing observations, adjustment for multiple outcomes, and details of any model-based analyses are not reported in the registry record.
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.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| 5-FU + Mitomycin + IMRT | 52 | 40 | 76.9% | 63.2% to 87.5% | 63.9% to 86.3% | 63.8% to 86.2% |
R code and output
arm <- c("5-FU + Mitomycin + IMRT")
n <- c(52)
events <- c(40)
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 5-FU + Mitomycin + IMRT 52 40 76.9 63.2 87.5 63.9 86.3 63.8 86.211. Multiplicity, Missing Data and Analysis Populations
The record lists 12 outcome measures and 7 analyses, including the primary acute gastrointestinal and genitourinary adverse-event endpoint and secondary outcomes covering radiation-planning deviations, acute and late adverse events, clinical complete response, treatment duration, survival, disease-free survival, and local-regional failure. Considering multiple outcomes can raise the chance of at least one apparently notable finding when many hypotheses are tested. In general, multiplicity methods can control that risk by adjusting how evidence is assessed or by defining a hierarchy of outcomes in advance. The registry does not report a multiplicity adjustment, a testing hierarchy, or whether all listed analyses were confirmatory.
The statistical analysis plan and any interim analyses are not reported in the registry record. It is therefore not possible to determine from this record whether analyses were prespecified, whether outcome definitions changed, or how repeated looks at accumulating data were handled.
The primary population is described as eligible patients with adverse-event information. The adverse-event summary separately gives 52 participants at risk, while enrollment is listed as 63. The record does not explain the difference or state how participants lacking endpoint information were handled. In general, missing outcome information can affect a percentage if participants with incomplete assessment differ from those with complete assessment. Methods such as imputation or sensitivity analyses may address some consequences under explicit assumptions, but their use in this trial is not reported in the registry record.
Other analysis-population details, including whether an intention-to-treat, per-protocol, or safety population was defined, are not reported in the registry record. The record also does not report how protocol deviations were handled in the endpoint analysis. These omissions limit assessment of which participants contributed to each reported outcome and whether exclusions could have influenced the results.
12. 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 |
|---|---|---|---|
| 5-FU + Mitomycin + IMRT | 6 | 52 | 11.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 5-FU + Mitomycin + IMRT | 52 of 52 |
Most frequent serious adverse event terms
| Event term | Organ system | 5-FU + Mitomycin + IMRT |
|---|---|---|
| Dehydration | Metabolism and nutrition disorders | 2 of 52 |
| Anemia | Blood and lymphatic system disorders | 1 of 52 |
| Atrial fibrillation | Cardiac disorders | 1 of 52 |
| Sinus bradycardia | Cardiac disorders | 1 of 52 |
| Abdominal pain | Gastrointestinal disorders | 1 of 52 |
| Constipation | Gastrointestinal disorders | 1 of 52 |
| Diarrhea | Gastrointestinal disorders | 1 of 52 |
| Enterocolitis | Gastrointestinal disorders | 1 of 52 |
| Esophagitis | Gastrointestinal disorders | 1 of 52 |
| Mucositis oral | Gastrointestinal disorders | 1 of 52 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 5-FU + Mitomycin + IMRT |
|---|---|---|
| Diarrhea | Gastrointestinal disorders | 42 of 52 |
| Anemia | Blood and lymphatic system disorders | 35 of 52 |
| Fatigue | General disorders | 33 of 52 |
| Neutrophil count decreased | Investigations | 33 of 52 |
| White blood cell decreased | Investigations | 33 of 52 |
| Platelet count decreased | Investigations | 32 of 52 |
| Dermatitis radiation | Injury, poisoning and procedural complications | 31 of 52 |
| Nausea | Gastrointestinal disorders | 28 of 52 |
| Mucositis oral | Gastrointestinal disorders | 25 of 52 |
| Anorexia | Metabolism and nutrition disorders | 19 of 52 |
Serious events with the highest arm-level rate: dehydration (3.8%), anemia (1.9%), atrial fibrillation (1.9%), sinus bradycardia (1.9%), abdominal pain (1.9%).
The registry’s serious adverse-event summary lists 6 affected participants among 52 at risk for the 5-FU, mitomycin, and IMRT group. A separate other-adverse-event category lists 52 affected participants among 52 at risk. These are descriptive safety entries. They are not the primary endpoint, which specifically concerns acute gastrointestinal and genitourinary events of at least grade 2 over the period from treatment start to 90 days.
The serious-event terms listed include dehydration at 3.8%, anemia at 1.9%, atrial fibrillation at 1.9%, sinus bradycardia at 1.9%, abdominal pain at 1.9%, and constipation at 1.9%. These percentages are reported as registry figures; they should not be converted into additional counts or treated as comparative risks. The record does not state in this summary whether a participant could appear under multiple terms.
Seriousness is not the same as CTCAE severity grade. In general, a serious adverse event is classified by its consequences or regulatory criteria, whereas a grade describes severity. The death entry is null, so a death count is not reported in the registry record; null should not be read as zero. No safety comparison with another regimen is available because the study has a single group.
13. What the Result Does, and Does Not, Mean
The trial is a phase II evaluation of intensity-modulated radiation therapy combined with fluorouracil and mitomycin C in patients with invasive anal cancer. Its primary question concerns the percentage of participants with acute gastrointestinal or genitourinary adverse events of at least grade 2 during the interval from treatment start to 90 days. The endpoint is clearly described, including the grading system and the rule to count each participant’s highest grade.
What the record does not establish is the numeric answer to that primary question. The primary endpoint’s percentage and 95% confidence interval are not reported in the registry record. Accordingly, the frequency and precision of the primary acute-toxicity outcome cannot be evaluated from this information. The separate serious and other adverse-event summaries supply some safety counts, but they do not answer the defined primary endpoint.
The record also does not establish whether this regimen produces better or worse outcomes than another treatment. The single-group design has no randomized comparator, and allocation is listed as not applicable. Any outcome observed within the group is descriptive of that group; it is not a randomized treatment contrast. The trial’s secondary outcomes include response, survival, disease-free survival, and local-regional failure, but numeric results for those outcomes are not included in the information.
In general, a confidence interval helps readers understand how much statistical uncertainty surrounds an estimate, while the design determines what comparisons the estimate can support. Neither an interval nor a large enrollment would remove the fundamental absence of a control group. Conversely, missing result details do not establish that an outcome was favorable or unfavorable; they mean that the relevant estimate cannot be assessed from the registry record.
The reported serious-event summary may be useful as a descriptive safety signal, but it cannot be interpreted as evidence of comparative safety. The record does not report the number of deaths, the handling of missing safety observations, or the analytic approach for the primary endpoint. Interpretation should remain limited to the definitions and descriptive safety figures that are explicitly recorded.
14. Why This Trial Matters Statistically
This trial illustrates why endpoint definitions and study design must be read together. The primary outcome is not simply “toxicity”: it specifies gastrointestinal and genitourinary adverse events, a threshold of at least grade 2, CTCAE v3.0 grading, a defined acute observation period, and a rule based on each participant’s highest grade. Those choices determine what the endpoint captures and what it leaves out.
The single-group design is equally important. It can describe outcomes among participants receiving the regimen, but it cannot supply a randomized comparison with another treatment. This distinction is central to biostatistical interpretation: a clearly defined outcome does not by itself provide causal evidence, and a result from a single group should not be read as a treatment effect relative to an unobserved control.
The record also demonstrates the difference between a protocol-level outcome description and an analyzable result. It identifies the primary endpoint and its intended confidence interval but does not report the endpoint’s numerical estimate or interval. Without those values, readers cannot assess either the observed event frequency or its statistical precision. Clear reporting of denominators, missing observations, and analysis methods would be needed for a fuller appraisal.
Finally, the safety listings show why event categories should not be collapsed casually. Serious-event status, CTCAE severity, and the primary threshold endpoint address different aspects of adverse events. Keeping these concepts separate helps prevent a descriptive safety summary from being mistaken for the primary outcome or a comparison of treatment risks.
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 most immediate limitation is incomplete outcome reporting in the registry record available for this analysis. The primary endpoint definition is stated, but its numeric percentage and 95% confidence interval are not reported. Numeric results for the secondary outcomes are likewise not included in the information. This prevents assessment of the magnitude and precision of the primary outcome and limits interpretation of the broader outcome set.
The single-group design provides no concurrent comparator. Allocation is listed as not applicable, and masking is listed as none. As a result, there is no randomized contrast on which to base a comparative estimate. The record does not report an external control analysis or describe assumptions for any such comparison.
Enrollment is listed as 63, while the adverse-event summary gives 52 at risk. The record does not explain the relationship between these figures or the reasons any participants may not have contributed to a particular summary. The primary population is described as eligible patients with adverse-event information, but details of missing-data handling and analysis-population definitions are not reported in the registry record.
The record lists multiple outcomes and analyses but does not report a statistical analysis plan, multiplicity strategy, or interim-analysis information. The interval method for the primary percentage is also not reported. These omissions make it difficult to assess prespecification, the handling of multiple outcomes, and the assumptions underlying reported estimates.
For safety, the serious-event listing includes participant counts and term percentages, but the death entry is null and no death count is reported in the registry record. The listing does not establish comparative safety, and the summary does not explain whether participants could contribute to multiple event terms. These limitations are specific to interpreting the available record and do not imply unreported outcomes or analyses.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Intensity-Modulated Radiation Therapy, Fluorouracil, and Mitomycin C in Treating Patients With Invasive Anal Cancer — NCT00423293.
- Registry record last updated 2019-02-27; status last verified 2019-02.
- Results first posted 2013-05-29.
- 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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19. Record Summary
NCT00423293 is a completed phase II, single-group trial sponsored by the Radiation Therapy Oncology Group. It evaluated intensity-modulated radiation therapy with fluorouracil and mitomycin C in patients with invasive anal cancer. Enrollment is listed as 63; the study started in 2006-12 and reached primary completion in 2009-02.
The primary endpoint was the percentage of participants with acute gastrointestinal and genitourinary adverse events of at least grade 2 under CTCAE v3.0, from treatment start to 90 days. The record describes the measure but does not report its numeric estimate or 95% confidence interval. The adverse-event listing reports 6 participants with serious events among 52 at risk and 52 with other adverse events among 52 at risk. With no randomized comparator, these safety entries are descriptive rather than comparative.