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 Temozolomide as a Prophylaxis Against Brain Recurrence in Participants With Metastatic Breast Cancer (P05225 AM2) (NCT00638963), a randomized phase 2 study. The primary outcome is Percent of Participants With Recurrence of Brain Metastases.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00638963 |
| Phase | Phase 2 |
| Condition | Breast Neoplasm, Brain Neoplasm, Second Neoplasm |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants with metastatic breast cancer considered at high risk of brain recurrence. The registry record gives the study population in those terms, but does not report eligibility details, how high risk was defined, or other baseline characteristics.
Intervention
Temozolomide, a drug intervention. The record does not provide a dosing schedule or treatment duration in the arm description.
Comparator
An observational group. The record does not describe what observation involved or whether participants in that group received other care.
Primary question
What percent of participants had recurrence of brain metastases within 1 Year? The registry record says this analysis could not be performed due to low enrollment, so it does not provide an estimated percentage or a comparison between the groups.
The study was intended to examine whether temozolomide could be used as prophylaxis against brain recurrence. That is the research question, not a conclusion about the drug. The record identifies a randomized, parallel-group phase 2 study with temozolomide and observational arms. It records six participants in total. Although randomization was part of the design, the small recorded enrollment and the lack of a primary endpoint analysis mean the registry does not establish the size or direction of any difference between groups.
The primary endpoint focuses on brain metastasis recurrence over a defined period. Other registered outcomes include progression-free survival, disease-free survival, distant disease-free survival, brain recurrence-free survival, and measures of temozolomide exposure and treatment modifications. The record does not report results for these outcomes. Therefore, the clinical question remains unanswered by the results recorded in the registry.
3. Trial Design
This was a phase 2, randomized, parallel-group study with no masking. The listed arms were temozolomide and observational. The registry describes temozolomide as a drug intervention but gives no further description of either arm. In particular, the observational arm's procedures and any permitted treatments are not reported in the registry record.
The record lists enrollment of 6 participants. It gives a start date of 2008-10-02 and a primary completion date of 2010-06-30, and the study status is terminated. These dates and status describe the registry entry; they do not explain why the study was terminated. The record does state that the primary endpoint analysis could not be performed due to low enrollment. A separate reason for termination is not reported in the registry record.
Random allocation is intended to assign participants to study groups by chance, which can reduce systematic differences between groups at the point of assignment. In a parallel-group design, participants are assigned to a group and evaluated within that group rather than switching between study treatments. These are general design concepts; the record does not report how randomization was generated, whether allocation was concealed, or how assignment was implemented.
The study was unmasked, meaning masking was not used according to the registry entry. The record does not describe how knowledge of assignment may have affected care, outcome assessment, or reporting. It also does not report the planned enrollment target, a sample-size justification, or detailed eligibility criteria. With only six participants recorded and no primary analysis, the design information alone cannot establish whether the intervention and observational groups differed in brain recurrence.
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 | Temozolomide | Observational |
|---|---|---|
| STARTED | 3 | 3 |
| COMPLETED | 2 | 3 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Temozolomide | Observational |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Temozolomide | Observational | Total |
|---|---|---|---|---|
| Participants analysed | 3 | 3 | 6 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 | 3 | 6 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 3 | 3 | 6 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Region of Enrollment: Italy | participants | 3 | 3 | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Percent of Participants With Recurrence of Brain Metastases, measured over 1 Year.
| 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 is the percent of participants with recurrence of brain metastases, assessed at 1 Year. It is directly tied to the study's stated question about using temozolomide as prophylaxis against brain recurrence in participants with metastatic breast cancer. A proportion with recurrence can describe how often the event was observed in a defined group over a defined period.
As a general statistical concept, a fixed-time proportion is interpretable only when the outcome status can be assessed for the participants relevant to that time point and the analysis approach is clear. Time-to-event outcomes can also account for the timing of recurrence and follow-up, but the registry record does not give an analysis method for the primary endpoint. It also does not report a numerator, a denominator for an endpoint analysis, an estimated percentage, or a comparison between the arms.
The registry explicitly states that the primary analysis could not be performed due to low enrollment. Therefore, the endpoint is defined, but its result is not available in the registry record. The record does not report an estimate of recurrence or the precision of an estimate, such as a confidence interval. The registered timeframe does not by itself show whether participants were followed for that full period or how incomplete follow-up was handled.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central statistical fact is that the intended primary endpoint analysis was not performed because of low enrollment. Although the study records six participants, the registry does not provide the percentage with brain metastasis recurrence at 1 Year, an arm-specific estimate, or a comparison between the temozolomide and observational groups. There is consequently no primary effect estimate to interpret and no reported measure of its precision.
The absence of an estimate is not evidence that the groups had the same recurrence experience. It also does not establish that recurrence was more common in either group. The registry record leaves the clinical question unresolved. A small enrollment can limit the information available to estimate an outcome, but the record does not provide enough information to quantify how much uncertainty would have remained under any particular analysis.
The listed secondary outcomes cover several kinds of information: time-to-event outcomes, duration and amount of temozolomide exposure, and treatment modifications. The record does not report results for these outcomes or statistical analyses of them. It therefore cannot support conclusions about progression-free survival, disease-free survival, distant disease-free survival, brain recurrence-free survival, or treatment exposure and modifications.
The adverse-event entry records 0 participants affected by serious adverse events in each group, with 3 at risk in each group. It also records 2 participants affected by other adverse events in each group, again with 3 at risk in each group. These are limited descriptive counts from a very small study record. The registry does not list serious adverse event terms, and deaths are not reported. The entries should not be interpreted as a complete characterization of safety or as a comparison with useful precision.
Randomization is a design feature, not a substitute for outcome information. With the primary analysis unavailable and no analyses listed in the registry record, there is no reported statistical test, confidence interval, or adjusted result to weigh. No finding about benefit, lack of benefit, or comparative safety can be inferred from the fact that an analysis was not performed.
9. Statistical Methods Explained
The registry identifies this as a randomized, parallel-group phase 2 study without masking. Those labels describe broad features of the design, not the details of the statistical analysis. The record does not report the randomization method, allocation concealment, planned analysis population, or a statistical analysis plan. Without those details, it is not possible to determine how the investigators intended to handle specific analysis choices.
What randomization can and cannot do
In general, randomization assigns participants to groups using chance. It is used to reduce systematic differences in participant characteristics between groups, so that an outcome contrast can be more credibly associated with the assigned study strategies. Randomization does not guarantee that groups will be alike in every characteristic, especially when few participants are enrolled. Nor does randomization create information about outcomes that were not analyzed or reported. In this study, the registry records six participants, but does not provide the primary outcome comparison.
A parallel-group design means that participants are assigned to one group for the study rather than crossing between groups. Here the listed groups are temozolomide and observational. The record does not state the procedures in the observational group, so the precise contrast between the groups cannot be described beyond those labels. The study is unmasked; in general, lack of masking can matter when decisions or outcome assessments could be influenced by knowledge of group assignment. The registry does not explain whether or how this issue was addressed.
How to interpret an endpoint estimate
In general, a percentage with an event describes the observed frequency in a defined population over a stated period. A comparison between groups would require estimates for both groups and a specified method for contrasting them. A confidence interval, when reported, describes the range of values compatible with the data and analysis under its statistical assumptions. Narrower intervals generally indicate greater precision, while wider intervals indicate less precision. No primary endpoint estimate or confidence interval is reported in this registry record, so precision cannot be evaluated.
The primary endpoint is recurrence of brain metastases at 1 Year. The registry says the analysis could not be performed due to low enrollment. That statement should be distinguished from a null result: a null result would still require an analysis and an estimate, while the registry reports no such analysis. It is also distinct from evidence of no difference, which would require estimates sufficiently informative to assess a difference. Neither is available in the record.
Time-to-event outcomes and follow-up
Several registered secondary outcomes are expressed as numbers of days until outcomes such as progression-free survival, disease-free survival, distant disease-free survival, and brain recurrence-free survival. In general, time-to-event methods are designed for outcomes where both whether an event occurred and when it occurred matter. They can incorporate participants whose follow-up ends before an event is observed, using methods that account for censoring. Censoring means the event time is not known beyond a participant's last observed follow-up; it does not mean that the participant had no event.
These general methods rely on clear definitions of events, follow-up, censoring, and analysis populations. The registry lists the outcomes but does not report their results or the methods used to analyze them. It does not describe follow-up completeness or how participants without a recorded event were handled. Those details are not reported in the registry record, so no time-to-event estimates can be reconstructed or assessed from this entry.
Small samples and uncertainty
In general, small samples often produce imprecise estimates because each participant's outcome can have a substantial influence on the observed result. For binary outcomes, such as whether recurrence occurred by a fixed time, the number of events and the number of participants assessed are important for understanding precision. For time-to-event outcomes, the number and timing of events and the follow-up information also matter. The registry gives no primary endpoint event counts or analysis denominator, and its statement that low enrollment prevented analysis means the primary outcome is not available for interpretation.
Over-dispersion is a general issue in some count-data settings: the observed variability can exceed the variability assumed by a simple model. Accounting for it can affect standard errors and confidence intervals. No count-data analysis or over-dispersion assessment is reported in this record, so this concept does not provide a basis for interpreting a study result.
Planning calculations versus study findings
In general, sample-size planning illustrations describe how many participants might be needed under stated assumptions about the target effect, significance level, allocation, and statistical method. They are planning exercises, not evidence about what the study observed. A calculation based on an observed effect is especially unsuitable as a claim about the original design when the primary analysis was not performed. The registry does not report a sample-size justification or planned enrollment target. Any planning illustration should therefore be read as a hypothetical calculation under its stated assumptions, not as an observed result or evidence that the study had adequate power.
The registry lists no statistical analyses. It does not report p-values, adjusted estimates, confidence intervals, interim analyses, multiplicity procedures, or a prespecified analysis plan. These absences limit the statistical interpretation: the available record describes the design and outcomes, but does not contain an inferential result for the primary question.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and multiple secondary outcomes, including several survival-related measures and measures of temozolomide exposure and treatment modifications. When a study examines several outcomes, general statistical practice recognizes that the chance of finding an apparently notable result can increase if many comparisons are tested. A multiplicity strategy may specify which outcomes are confirmatory, how tests are ordered, or how statistical thresholds are adjusted. Such a strategy is not reported in the registry record.
The registry lists no statistical analyses, and it does not report results for the primary or secondary outcomes. It therefore does not show whether any multiplicity adjustment was planned or applied. The absence of a reported adjustment should not be interpreted as proof that no adjustment was considered outside the registry; the relevant information is not reported in the registry record.
Details about missing outcome data are also not reported. The record does not describe follow-up completeness, withdrawals, censoring, imputation, or sensitivity analyses. These details matter because incomplete observation can affect which participants contribute to an endpoint estimate and how uncertainty is assessed. The primary endpoint analysis was not performed due to low enrollment, but the registry does not specify whether missing data contributed to that decision.
The analysis population is not reported in the registry record. It does not say whether the planned analysis was based on all randomized participants, participants who received treatment, or another defined group. Nor does it describe how participants were to be analyzed if they did not follow their assigned group. With no analysis population or endpoint analysis stated, the record does not permit an assessment of these choices.
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 |
|---|---|---|---|
| Temozolomide | 0 | 3 | 0.0% |
| Observational | 0 | 3 | 0.0% |
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 |
|---|---|
| Temozolomide | 2 of 3 |
| Observational | 2 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Temozolomide | Observational |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 2 of 3 | 0 of 3 |
| Diarrhoea | Gastrointestinal disorders | 1 of 3 | 0 of 3 |
| Vomiting | Gastrointestinal disorders | 1 of 3 | 0 of 3 |
| Asthenia | General disorders | 1 of 3 | 0 of 3 |
| Chest pain | General disorders | 0 of 3 | 1 of 3 |
| Influenza like illness | General disorders | 1 of 3 | 0 of 3 |
| Pyrexia | General disorders | 1 of 3 | 0 of 3 |
| Myalgia | Musculoskeletal and connective tissue disorders | 1 of 3 | 0 of 3 |
| Insomnia | Psychiatric disorders | 1 of 3 | 0 of 3 |
| Vulvovaginal dryness | Reproductive system and breast disorders | 0 of 3 | 1 of 3 |
The registry reports serious adverse event figures separately for the temozolomide and observational groups. Each group has 3 participants at risk and 0 affected by serious adverse events. For other adverse events, each group has 3 participants at risk and 2 affected. These are descriptive counts in the registry record; they are not estimates of comparative safety with useful statistical precision.
The entry does not list serious adverse event terms. It also does not report deaths. These omissions mean the listed counts do not describe the types, timing, severity details, or outcomes of individual events. The record does not clarify the ascertainment procedures or the duration over which adverse events were monitored.
With so few participants recorded, the absence of a serious adverse event entry in a group should not be read as proof that serious harms cannot occur. Similarly, matching counts of other adverse events do not establish equivalent safety between groups. The figures describe what the registry records for this study, not a general estimate applicable beyond its participants.
12. What the Result Does, and Does Not, Mean
The registry record documents a phase 2 randomized study intended to assess temozolomide as prophylaxis against brain recurrence in metastatic breast cancer. It records six participants and identifies a primary endpoint: the percent with recurrence of brain metastases at 1 Year. It also states that this primary analysis could not be performed due to low enrollment.
That leaves the key result unknown in the registry. There is no reported recurrence percentage, no arm-specific estimate, and no reported comparison between temozolomide and the observational group. The record therefore does not show whether recurrence was more or less frequent in either group, and it does not support a conclusion that the groups were similar. An unavailable analysis is not a negative finding.
The registry also does not report results for the listed secondary outcomes. The available adverse-event entries report 0 serious adverse events among 3 at risk in each group and 2 participants affected by other adverse events among 3 at risk in each group. These small descriptive counts do not establish a comparative safety profile, and deaths are not reported.
The study's randomized design is relevant to how a comparison might have been conducted, but design labels cannot replace outcome estimates. The record does not provide uncertainty intervals, statistical tests, analysis populations, or details of missing data and follow-up. As a result, the precision and robustness of any treatment comparison cannot be evaluated from the registry entry.
The appropriate interpretation is limited: the study set out to ask a clinically focused question, but the registry does not contain an analyzable primary result. It does not establish that temozolomide prevents brain recurrence, nor does it establish that it does not. The clinical question remains unresolved in the reported record.
13. Why This Trial Matters Statistically
This study illustrates an important distinction between a registered research question and an answer supported by reported data. The registry describes a randomized comparison and defines a primary endpoint, but also states that the endpoint analysis could not be performed because enrollment was low. Statistical interpretation depends on estimates and their uncertainty, not only on the intended design or the presence of a stated outcome.
Enrollment of 6 participants leaves little information for describing outcomes across the groups. The adverse-event entry records 3 at risk in each group, but the primary endpoint result is absent. Without recurrence counts and an analysis method, readers cannot quantify an effect, assess its precision, or determine whether observed group differences—if any—could plausibly reflect chance variation.
The record also highlights why a randomized design does not guarantee a conclusive study. Random allocation can help make groups comparable, but it cannot compensate for an outcome analysis that was not performed. Nor can the study's phase label or list of secondary outcomes establish a result.
For biostatistical interpretation, the case underscores the need to distinguish unobserved or unanalyzed outcomes from analyzed outcomes that show little evidence of a difference. It also shows why transparent reporting of analysis populations, follow-up, missing data, and statistical methods is essential. Those details are not reported in the registry record, and the primary outcome is explicitly unavailable. The resulting conclusion is not that one group performed better or worse, but that the recorded evidence does not answer the study's primary 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 primary endpoint analysis was not performed because of low enrollment. The record lists six participants, but does not provide an endpoint denominator, recurrence counts, or group-specific primary outcome estimates. It is therefore not possible to assess the magnitude or precision of a difference between the groups.
The registry record does not report baseline characteristics or detailed eligibility criteria. Although the population is described as metastatic breast cancer patients at high risk of brain recurrence, the way high risk was defined is not stated. The arm descriptions provide no further details about the treatment schedule or the observational group's procedures. These omissions limit understanding of the enrolled population and the exact comparison.
Methods needed to evaluate the analysis are also not reported, including the randomization implementation, planned analysis population, missing-data handling, and statistical analysis plan. The registry lists no statistical analyses and provides no results for the registered secondary outcomes. Follow-up completeness and the handling of participants who may not have been observed through 1 Year are not reported in the registry record.
The safety entries are limited to affected counts and numbers at risk. Serious event terms are not listed, and deaths are not reported. The record does not give further details about adverse-event ascertainment or monitoring duration. These limitations mean the safety figures should be treated as a narrow description of the registry entry, not as a complete evaluation.
The study status is terminated, but a reason for termination is not reported in the registry record. The reason should not be inferred from the low enrollment statement, which specifically explains why the primary endpoint analysis could not be performed.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Temozolomide as a Prophylaxis Against Brain Recurrence in Participants With Metastatic Breast Cancer (P05225 AM2) — NCT00638963.
- Registry record last updated 2017-06-14; status last verified 2017-05.
- Results first posted 2011-07-22.
- 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
The registry describes a phase 2, randomized, parallel-group study without masking, comparing temozolomide with an observational group in participants with metastatic breast cancer at high risk of brain recurrence. Enrollment was 6. The study start date is 2008-10-02, the primary completion date is 2010-06-30, and the status is terminated.
The primary endpoint was the percent of participants with recurrence of brain metastases at 1 Year. The registry states that the analysis could not be performed due to low enrollment. It lists secondary outcomes covering survival-related measures and temozolomide treatment and exposure, but does not report their results or any statistical analyses.
For adverse events, the registry records 0 participants affected by serious adverse events among 3 at risk in each group, and 2 affected by other adverse events among 3 at risk in each group. Serious event terms and deaths are not reported. The primary clinical comparison and its statistical precision remain unavailable in the registry record.