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 Phase I Study of Intensity Modulated Radiation Therapy for Prostate Cancer (NCT00124917), a na phase 1 study. The primary outcome is Maximum Tolerated Dose (MTD) of External Beam Radiation.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00124917 |
| Phase | Phase 1 |
| Condition | Prostate Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
The planned population was patients with prostate cancer without evidence of metastasis. The registry record reports 6 participants enrolled. It does not report further eligibility details or describe the characteristics of the enrolled participants, so the degree to which they represent other patients with prostate cancer cannot be assessed from this record.
Intervention
The intervention was external beam radiation delivered with intensity modulated radiation therapy (IMRT). The planned approach was to escalate dose to regions of histologically confirmed prostate cancer. Anatomic and biological magnetic resonance imaging, including magnetic resonance spectroscopy, and tissue sampling were described as part of the design; whether these procedures were completed is not reported in the registry record.
Comparator
There was no comparator group. The study is described as a single-group phase I trial, with no allocation and no masking. All 6 participants received a dose of 7560 cGy and were grouped together in one arm. As a result, the record does not support a direct comparison between radiation doses or between radiation and another treatment.
Primary question
The planned primary question was what maximum dose of external beam radiation could be given while meeting the protocol’s acute-toxicity criterion. The registry definition places the maximum tolerated dose at the level immediately below a dose level where 2 or more participants in a cohort of either 3 or 6 experienced radiation-attributed dose-limiting toxicity. The primary outcome was not done, so the record does not establish a maximum tolerated dose.
This is a dose-finding question, rather than a test of whether radiation is better than a control treatment. A dose-escalation study seeks information about tolerability at planned dose levels. The recorded result needs to be read in light of what was actually achieved: all participants received 7560 cGy, and an attempt was made to escalate to the next higher dose, but participants could not be treated while maintaining safety standards. The record does not report the toxicity observations by dose cohort needed to apply the stated endpoint definition. It therefore describes the intended question and the treatment delivered, but not a completed estimate of the dose threshold.
3. Trial Design
This was a phase I, single-group study sponsored by the National Cancer Institute (NCI). The registry lists no allocation and no masking. Its planned approach was a standard 3-6 dose-escalation design: an initial cohort of 3 participants at each dose level, with a cohort potentially expanded to 6. Radiation was to be delivered with IMRT to histologically confirmed regions of prostate cancer. The stated scientific objective was to determine the maximum tolerated dose based on acute toxicity.
The design also described an imaging and tissue component. Anatomic magnetic resonance imaging and biological magnetic resonance images, such as magnetic resonance spectroscopy, were to be obtained. Tissue was to be acquired from sites of interest, with biopsy locations co-registered to a reference MR image. The registry record does not report whether these procedures were completed or how their measurements were analyzed.
The recorded conduct differs from the planned dose-escalation sequence in an important way: all 6 enrolled participants received 7560 cGy and were grouped together in one arm. The record says that an attempt was made to escalate to the next higher dose, but that it was not possible to treat participants and maintain safety standards. It does not report the number treated at each planned cohort level, the dose-limiting toxicity observations by cohort, or the reason the next dose could not be given beyond that safety statement.
The trial started on 2005-07-21, had a primary completion date of 2011-03-06, and is listed as terminated. The reason for termination is not reported in the registry record. The study is therefore not a randomized comparison and does not provide a like-for-like control group. Its stated design was exploratory and dose-finding; the actual recorded results describe one dose group and adverse-event counts, while the primary outcome was not done.
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: All 6 participants enrolled in this trial received a dose of 7560 cGy and are grouped together in one Arm/Group. An attempt was made to escalate to the next higher dose but we were unable to treat patients and maintain safety standards.
Overall Study
| Stage | Radiation Therapy - 7560 cGY |
|---|---|
| STARTED | 6 |
| COMPLETED | 3 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Radiation Therapy - 7560 cGY |
|---|---|
| Physician Decision | 3 |
Analysis population for the primary outcome, as defined in the registry: This outcome measure was not done. All 6 participants enrolled in this trial received a dose of 7560 cGy and are grouped together in one Arm/Group. An attempt was made to escalate to the next higher dose but we were unable to treat patients and maintain safety standards.
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 6 participants enrolled in this trial received a dose of 7560 cGy and are grouped together in one Arm/Group. An attempt was made to escalate to the next higher dose but we were unable to treat patients and maintain safety standards.
| Characteristic | Unit | Radiation Therapy - 7560 cGY |
|---|---|---|
| Participants analysed | 6 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 4 |
| Age, Continuous | years | 68.17 (SD 10.07) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 6 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 6 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of External Beam Radiation, measured over 12 weeks after radiation therapy (RT).
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the maximum tolerated dose (MTD) of external beam radiation. The registry defines this as the dose level immediately below the level at which 2 or more participants in a cohort of either 3 or 6 experienced a dose-limiting toxicity attributed to radiation therapy. The listed timeframe was 12 weeks after radiation therapy (RT). The protocol’s stated objective was to determine the MTD based on acute toxicity.
In general, an MTD endpoint is used in dose-finding research to identify a dose boundary under a prespecified toxicity rule. It is not a direct measure of comparative benefit. The endpoint depends on observing toxicity at successive dose levels and assigning events to the treatment under the protocol’s attribution rules. Those cohort-level observations are essential for applying the definition; a single pooled group at one dose does not, by itself, locate the dose level immediately below a toxicity threshold.
In this record, the outcome measure is explicitly described as not done. All 6 participants received 7560 cGy, and the record notes an unsuccessful attempt to proceed to the next higher dose while maintaining safety standards. No MTD estimate, dose-limiting-toxicity count by cohort, or endpoint analysis is reported. Thus, the endpoint definition explains what the trial intended to estimate, but the registry record does not report a result for that endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The main statistical point is that the planned primary outcome and the recorded study results are not the same thing. The trial planned to estimate a maximum tolerated dose through dose escalation and an acute-toxicity rule. The registry states that this outcome was not done. It reports that all 6 participants received 7560 cGy in one arm, and that an attempt to escalate to the next higher dose could not be carried out while maintaining safety standards. These registry entries do not amount to an MTD estimate under the stated definition.
The single-group design also limits the kind of inference available. There is no control group and no randomized dose comparison. The record cannot show how outcomes would have differed under another dose or treatment. Further, the participants were grouped together at one recorded dose, rather than reported across the dose cohorts needed to apply the planned escalation rule. This makes it important not to treat the study as a comparative efficacy trial.
The safety results are counts in the Radiation Therapy - 7560 cGY group. One participant is reported as having a serious adverse event, and 3 participants are reported as having non-serious adverse events. Deaths are reported as 0. The top serious term is Mood alteration:: Depression, listed as 16.7%. The record does not report details sufficient to establish whether these events were attributed to radiation, how long adverse events were collected, or whether the events overlap across seriousness categories. The counts should therefore be read as recorded safety information, not as a complete causal assessment.
No inferential analyses are listed. The registry record does not report a confidence interval, p-value, dose-response estimate, or statistical comparison for the primary outcome. The absence of an inferential result means that the precision of an MTD estimate cannot be assessed; in this case, the primary outcome itself was not done. A confidence interval, in general, describes a range of values compatible with data and an analysis method, but no such interval for the MTD is reported.
The record also does not report a statistical analysis plan, a rationale for the planned enrollment, interim analysis procedures, or handling of missing observations. These omissions do not establish what methods were or were not used during conduct; they mean that those methods are not reported in the registry record. The reported enrollment of 6 is small in absolute terms, and the design was intended for dose finding rather than a broad comparative assessment. Any planning illustrations should be understood as hypothetical calculations, not as observed power or evidence that the primary endpoint was completed.
Overall, the posted results give limited descriptive information about the one recorded dose group and state that the intended primary endpoint was not done. They do not establish a maximum tolerated dose, a comparative treatment effect, or a complete account of safety across escalating doses. Interpretation should remain within those boundaries.
9. Statistical Methods Explained
Statistical interpretation starts with the question the study was designed to answer. This trial’s primary objective was dose finding: identify an external beam radiation dose satisfying a stated acute-toxicity rule. It was not designed as a randomized comparison between treatments. The design description calls for dose escalation, beginning with cohorts of 3 and potentially expanding a cohort to 6. In general, such designs use observed toxicities at a dose level to guide whether escalation, expansion, or stopping is appropriate. The exact decision process beyond the stated MTD definition is not reported in the registry record.
What does the MTD rule mean?
The registry defines the maximum tolerated dose as the dose level immediately below a dose level at which 2 or more participants in a cohort of either 3 or 6 have a dose-limiting toxicity attributed to radiation therapy. This is a rule-based endpoint. To apply it, the analysis needs the dose levels administered, the number of participants assessed at each level, and the qualifying toxicity observations and attribution at each level. General statistical practice distinguishes this kind of dose threshold from an average treatment effect: it is about a protocol-defined boundary across doses, not a comparison with an untreated or alternative-treatment group.
The record states that all 6 participants received 7560 cGy and that the primary outcome was not done. An attempt was made to move to the next higher dose, but the record says that participants could not be treated while maintaining safety standards. Since cohort-specific toxicity results and an endpoint estimate are not reported, the planned decision rule cannot be reconstructed from the posted results. No assumption should be made about what happened at unreported dose levels.
Why does the single-group structure matter?
A single-group study can describe outcomes among people who received the intervention, but it does not offer a concurrent control group for estimating a treatment contrast. General statistical explanation: randomization supports comparisons by balancing, on average, known and unknown baseline factors across assigned groups. With no allocation and no control arm in this record, there is no randomized contrast to interpret. The actual results place the participants in one arm at 7560 cGy, so they also do not report outcomes across multiple dose groups. The study’s dose-finding aim should not be confused with a trial comparing clinical outcomes between treatments.
What can adverse-event counts show?
Counts provide descriptive information about the number of participants recorded with events in the stated group. The registry reports 1 participant with a serious adverse event, 3 with non-serious adverse events, and 0 deaths in the Radiation Therapy - 7560 cGY group. It lists Mood alteration:: Depression as the top serious term at 16.7%. These summaries do not, on their own, show whether an event was caused by the intervention, its timing, severity details beyond the serious/non-serious classification, or whether it occurred alongside another event. Those details are not reported in the registry record.
In general, small event counts have limited precision: a count can change substantially in relative terms when the number of participants is small. This is a general statistical consideration, not an additional calculated result for this trial. The registry’s safety counts should be read as observed descriptive data for the recorded group, not as a precise estimate of event risk across a broader population or across doses not administered.
What is not available for inferential assessment?
The registry lists 0 analyses. No p-value, confidence interval, dose-response model, or statistical estimate for the primary endpoint is reported. In general, a confidence interval communicates uncertainty around an estimate under specified assumptions. Without a reported MTD estimate and an analysis method, there is no interval to interpret for that endpoint. A p-value would address a particular statistical hypothesis under a specified model; no such test result is reported. The record does not report the statistical analysis plan, sample-size justification, interim analyses, or rules for handling missing observations.
Planning illustrations are different from results. General sample-size calculations depend on assumptions about the design, outcome, target effect, and error rates. The calculations associated with the posted material are described as illustrations using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and fractions of an observed effect. Such assumptions do not describe the actual single-group dose-escalation design, and planning sample sizes are not observed power. The registry record does not report a completed primary outcome or an observed effect for the MTD question. The illustrative calculations therefore cannot be treated as evidence that the trial had a particular probability of detecting an effect or of reaching an MTD conclusion.
Finally, analysis populations require clear definitions, such as who was enrolled, treated, assessed for toxicity, or included in a particular analysis. The record reports 6 enrolled participants and states that all received 7560 cGy. It does not report a separate analysis-population definition, exclusions, missing-data methods, or participant-level outcome data. That limits independent checking of how the descriptive results were assembled.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a statistical analysis plan describing how multiple outcomes or multiple statistical tests were to be handled. It lists a primary MTD outcome and a secondary outcome for the number of participants with serious and non-serious adverse events. The trial description also names secondary objectives concerning gene and protein expression in relation to response and toxicity, and the frequency of late-term toxicity. Whether all of those objectives were measured or analyzed is not reported in the registry record.
Multiplicity is a general statistical concern when several outcomes, time points, dose levels, or hypotheses are examined. Without a prespecified analysis approach, readers cannot determine whether any reported inferential findings would account for the number of comparisons. The registry lists 0 analyses, and it does not report p-values or a multiplicity adjustment. No claim about an adjustment having been used or omitted during trial conduct can be made from this record.
Missing-data methods and the handling of participants not evaluable for toxicity are not reported in the registry record. The record reports 6 enrolled participants and says that all 6 received 7560 cGy, but it does not describe completeness of follow-up for each outcome, reasons for any unavailable measurements, or imputation methods. It also does not give an analysis-population definition beyond the reported enrollment and treatment information. These reporting gaps matter because dose-finding decisions depend on the evaluability and toxicity classification of participants at each dose level.
The MTD outcome was not done, so the record does not report an analysis population or missing-data approach for that endpoint. The available information is insufficient to determine whether unreported outcome data were never collected, were collected but not analyzed, or were omitted from 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 |
|---|---|---|---|
| Radiation Therapy - 7560 cGY | 1 | 6 | 16.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Radiation Therapy - 7560 cGY | 0 of 6 |
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 |
|---|---|
| Radiation Therapy - 7560 cGY | 3 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Radiation Therapy - 7560 cGY |
|---|---|---|
| Mood alteration:: Depression | Nervous system disorders | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Radiation Therapy - 7560 cGY |
|---|---|---|
| Renal/Genitourinary - Other, Dysuria | Renal and urinary disorders | 3 of 6 |
| Weight gain | General disorders | 3 of 6 |
| Erectile dysfunction | Reproductive system and breast disorders | 3 of 6 |
| Constipation | Gastrointestinal disorders | 2 of 6 |
| Libido | Reproductive system and breast disorders | 2 of 6 |
| Mood alteration::Depression | Nervous system disorders | 2 of 6 |
| Renal/Genitourinary - Other, Weak stream | Renal and urinary disorders | 2 of 6 |
| Urinary frequency/urgency | Renal and urinary disorders | 2 of 6 |
| Bladder spasms | Renal and urinary disorders | 1 of 6 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 6 |
Serious events with the highest arm-level rate: mood alteration:: depression (16.7%).
For the Radiation Therapy - 7560 cGY group, the registry reports 1 participant with a serious adverse event among 6 at risk and 3 participants with non-serious adverse events among 6 at risk. Deaths are reported as 0. The top serious term is Mood alteration:: Depression, listed at 16.7%. These are descriptive summaries for the recorded group, not comparisons against another dose or a control group.
The at-risk counts identify the number of participants represented in the registry’s safety summary. They do not establish the timing, duration, recurrence, or treatment attribution of each event. The record does not report whether the same participant could contribute to both the serious and non-serious counts, nor does it provide a full event-level account or the criteria used to assess causality. A listed serious term should not be read as proof that radiation caused that event.
Safety counts can help describe what was recorded among participants treated at this dose, but they cannot establish safety across a dose-escalation sequence that is not reported as completed. In particular, the primary MTD outcome was not done, and no cohort-by-cohort dose-limiting-toxicity analysis is reported. The available adverse-event figures should therefore be interpreted as limited descriptive information, rather than as a completed dose-threshold assessment.
12. What the Result Does, and Does Not, Mean
The record establishes that this phase I study enrolled 6 participants and that all 6 received 7560 cGy in a single recorded arm. It also states that an attempt was made to escalate to the next higher dose, but that it was not possible to treat participants while maintaining safety standards. The trial is listed as terminated. These details describe the treatment delivered and the status of the planned escalation; they do not establish the reason for termination beyond the stated safety constraint on further treatment.
The primary endpoint was intended to identify a maximum tolerated dose according to a defined acute-toxicity rule. The registry explicitly says that the outcome measure was not done. Consequently, the posted results do not establish an MTD, do not show the dose-limiting-toxicity pattern across cohorts, and do not support a dose-response conclusion. The one recorded dose group is not a substitute for the sequence of dose cohorts needed by the planned rule.
The adverse-event figures provide a limited account of recorded safety outcomes among those treated at 7560 cGy. They are not a comparison with another intervention and do not show that the intervention caused any particular event. The record also does not provide the detail needed to assess late-term toxicity or to evaluate the stated gene and protein expression objectives.
In general, a phase I dose-finding study is designed to answer a different question from a randomized trial designed to compare treatment outcomes. Its purpose and evidence need to be judged against its endpoint and the data actually reported. Here, the intended dose-finding endpoint was not completed, and no inferential analysis is listed. The record therefore cannot be used to claim a comparative treatment effect or to draw a conclusion about the maximum dose under the protocol definition.
The study still documents a planned imaging-guided dose-escalation approach and the experience of treating one group at the recorded dose. But the extent to which the imaging and tissue components were completed, and what they showed, is not reported in the registry record. The central statistical conclusion is narrow: the registry reports treatment and some safety counts, while the primary result needed to answer the stated dose-finding question is unavailable because the outcome was not done.
13. Why This Trial Matters Statistically
This trial illustrates why it is important to distinguish a protocol objective from a reported result. A defined endpoint does not become an estimate simply because it appears in the study description. Here, the MTD rule is explicit, but the registry says the outcome was not done. The record’s report that all participants received 7560 cGy and that a higher dose could not be pursued while maintaining safety standards provides important context, but it does not supply the cohort-level toxicity information or endpoint estimate needed to apply the rule.
The study also shows how design and analysis are linked. A planned dose-escalation design depends on observations organized by dose level. When the recorded participants are grouped into one arm at one dose, the posted results cannot describe the intended escalation sequence. A single-group design is appropriate to recognize as a dose-finding structure, not as evidence from a controlled treatment comparison.
Finally, this record is a useful reminder that safety summaries and primary endpoint results answer different questions. Counts of serious and non-serious events describe what was recorded for the treated group; they do not by themselves identify a maximum tolerated dose or establish causation. Clear reporting of dose cohorts, toxicity definitions, evaluability, and the analysis process is especially important in dose-finding work. Several of those details are not reported in the registry record, which limits how independently the intended statistical decision can be assessed.
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 trial-specific limitation is that the primary MTD outcome was not done. The record reports one treatment group at 7560 cGy for all 6 participants and does not provide outcomes by planned dose cohort. The stated MTD definition requires a toxicity threshold at a dose level and identifies the MTD as the immediately lower level. The posted information does not supply the cohort-specific observations needed to apply that rule.
The single-group structure offers no randomized control or alternative-dose group for direct comparison. Although the plan described dose escalation, the record says that an attempt to move to the next higher dose could not be carried out while maintaining safety standards. The record does not report the reason for termination or the details of the decision beyond this statement.
The enrollment was 6, and the safety summaries are limited to counts for the recorded dose group. The record does not provide participant-level events, timing, duration, event attribution, or an account of overlap between seriousness categories. It also does not report follow-up completeness, missing-data handling, or an analysis-population definition for the outcomes.
The stated imaging, tissue, gene-expression, protein-expression, and late-toxicity objectives are not accompanied by reported results in the record. The statistical analysis plan, interim analyses, and sample-size justification are also not reported in the registry record. These limitations constrain interpretation of the posted results; they do not establish that an unreported procedure or analysis was not undertaken.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase I Study of Intensity Modulated Radiation Therapy for Prostate Cancer — NCT00124917.
- Registry record last updated 2019-09-13; status last verified 2019-09.
- Results first posted 2019-09-13.
- 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 terminated phase I study evaluated an intended IMRT dose-escalation approach for prostate cancer. The planned primary endpoint was the maximum tolerated dose based on acute toxicity, defined using a cohort threshold of 2 or more dose-limiting toxicities. The registry states that the primary outcome was not done.
All 6 enrolled participants received 7560 cGy and were grouped in one arm. The record says an attempt to escalate to the next higher dose could not be made while maintaining safety standards. It reports 1 participant with a serious adverse event, 3 with non-serious adverse events, and 0 deaths; the top serious term is Mood alteration:: Depression at 16.7%. No analyses are listed, and no control group or MTD estimate is reported. The reason for termination and the statistical analysis plan are not reported in the registry record.