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 Liposomal Cytarabine and High-Dose Methotrexate in Treating Patients With Central Nervous System Metastases From Breast Cancer (NCT00992602), a na phase 2 study. The primary outcome is Survival Free of Neurological Progression, Measured in Weeks.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00992602 |
| Phase | Phase 2 |
| Condition | Central Nervous System Metastases, Leptomeningeal Metastases, Recurrent Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 3 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Washington |
| Results posted | Yes |
2. Clinical Question
Population
Patients with breast cancer involving the central nervous system were the intended population. The official title specifies patients with leptomeningeal metastases, with or without parenchymal brain involvement. The listed conditions also include recurrent and stage IV breast cancer and tumors metastatic to the brain. The registry record reports enrollment of 3 but does not give further detail about the characteristics of the enrolled participants.
Intervention
The study examined a combination of liposomal cytarabine and high-dose methotrexate. The official title describes intrathecal liposomal cytarabine. The registry also lists a quality-of-life assessment and laboratory biomarker analysis as interventions, but does not report their findings in the information available in the record.
Comparator
There was no separate comparator group. The study is registered as a single-group trial with no allocation, and its treatment arm is described as receiving liposomal cytarabine and high-dose methotrexate. Outcomes therefore describe participants in that group; they do not provide a randomized estimate of how the combination compares with another treatment or with no treatment.
Primary question
The primary endpoint was survival free of neurological progression, measured in weeks. Neurological progression could be defined by clinical impression using Karnofsky Performance Status, radiographical response using Macdonald criteria, or cytologic response using cerebrospinal fluid cytology. The registry specifies a median and a 95% confidence interval, but the endpoint result is not reported in the registry record. Consequently, the record does not allow a numerical description of the observed time to neurological progression or its precision.
3. Trial Design
This was a phase II study of a combination of high-dose methotrexate and intrathecal liposomal cytarabine for patients with leptomeningeal metastases, with or without parenchymal brain involvement. It is registered as a single-group study, with no allocation and no masking. The treatment arm is titled liposomal cytarabine and high-dose methotrexate. The record lists University of Washington as sponsor and gives the status as completed.
The record reports enrollment of 3. The study start is listed as 2011-04 and primary completion as 2013-06. These registry dates describe the study timeline; they do not provide a participant-level follow-up schedule or establish when each participant was observed. The primary endpoint timeframe is time from start of therapy, assessed up to 4 years.
A single-group design can describe outcomes among people receiving the study regimen, but does not create a concurrent control group. Without a randomized or otherwise comparable group, differences from another treatment cannot be attributed to the regimen on the basis of this design alone. The registry record does not report the detailed treatment schedule; the arm description directs readers to the detailed description. It also does not report a sample-size justification, interim-analysis plan, or detailed statistical analysis plan. The small enrollment and the absence of a reported primary endpoint estimate mean the design description alone cannot establish the observed efficacy or precision of the outcome.
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 | Treatment (Liposomal Cytarabine, High-dose Methotrexate) |
|---|---|
| STARTED | 3 |
| COMPLETED | 0 |
| NOT COMPLETED | 3 |
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 | Treatment (Liposomal Cytarabine, High-dose Methotrexate) |
|---|---|---|
| Participants analysed | 3 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 3 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 3 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 |
| 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 | 3 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Survival Free of Neurological Progression, Measured in Weeks, measured over Time from start of therapy, assessed up to 4 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | weeks |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is survival free of neurological progression, measured in weeks. It is a time-to-event outcome: the event is neurological progression, and the measure concerns the time from therapy start until progression. The record specifies that progression could be identified through clinical impression measured by Karnofsky Performance Status, radiographical response using Macdonald criteria, or cytologic response measured by cerebrospinal fluid cytology. The listed assessment timeframe is up to 4 years.
The registry specifies the median as the summary measure and a 95% confidence interval as its measure of uncertainty. In general, a median time-to-event measure describes the point by which half of the observed time distribution has experienced the event, subject to the analysis and handling of participants whose event time is not observed. A confidence interval conveys uncertainty around an estimate; it is not a guarantee that the true value lies within the interval.
Time-to-event endpoints are commonly used when both whether an event occurs and when it occurs matter. They can also accommodate differing observed follow-up through methods that account for censoring, if those methods are used and appropriately reported. The registry record does not give the median, confidence interval, event count for this endpoint, censoring information, or method of estimation. The endpoint's numerical result and precision are therefore not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically defined primary endpoint and names the treatment combination, but it does not report the primary endpoint estimate. It specifies survival free of neurological progression in weeks, summarized by a median with a 95% confidence interval, yet neither the median nor its interval is reported in the registry record. There is therefore no numerical primary result to interpret for duration or precision.
Enrollment was 3, and the design was single-group. This is important for interpreting any outcome: an outcome observed among treated participants would describe that group, not the effect of treatment relative to a concurrent control. No randomized comparison is registered. The study cannot, from this record, distinguish the effect of the treatment combination from other possible explanations for an observed outcome.
The listed neurological progression definition incorporates clinical impression, imaging criteria, or cerebrospinal fluid cytology. Those sources can capture different aspects of disease status. The record does not specify how a disagreement among them was handled, how often participants were assessed, or which criterion triggered an event when findings differed. Such details matter because event classification and timing influence a time-to-event estimate.
The record lists 3 participants at risk for serious adverse events, 0 with serious adverse events, 3 at risk for other adverse events, and 2 with other adverse events. It also lists 3 deaths. These are descriptive counts in the treatment group. The record does not give timing, causes, relationship to treatment, or a definition for the other adverse-event category, so those details should not be inferred from the counts. The death count is not itself a reported primary endpoint result.
Overall, the registry supports describing the study design, enrollment, endpoint definition, and recorded safety counts. It does not support a numerical estimate of neurological-progression-free survival or a comparative treatment conclusion. The lack of a reported endpoint result is a limitation of the information in the registry record, not evidence that the outcome was either favorable or unfavorable.
9. Statistical Methods Explained
The statistical interpretation of this study depends first on the distinction between a single-group description and a comparative treatment effect. The study is registered as single-group, with no allocation or masking. Its endpoint can be described within the treated group, but a treatment-versus-control contrast is not available from this design. The registry record does not report a statistical analysis plan that would add a comparative framework.
What does a median time-to-event result describe?
For a time-to-event outcome, each participant contributes information about time from a defined origin to an event, or to the last time the event status is known. In this study, the specified origin is therapy start and the event is neurological progression. The registered summary is the median time to progression-free survival, expressed in weeks. In general, the median marks the point in the estimated event-time distribution at which the event-free proportion reaches the midpoint. It is not an average, and it does not mean that every participant experienced an event at that time.
Some participants may not have a recorded event by the end of observation. In general, time-to-event methods can retain information from such participants by accounting for censoring, rather than treating their last observed time as an event time. The registry record does not report whether censoring occurred, how it was handled, or which estimation method was used. It also does not report the median estimate itself, so the method’s result cannot be checked or interpreted numerically.
What does the confidence interval add?
A confidence interval expresses statistical uncertainty around an estimated quantity under the assumptions of the method used. A narrower interval generally indicates greater precision, while a wider interval indicates greater uncertainty. It does not describe the range of individual participant outcomes, and it does not account for every possible source of bias. The registry specifies a 95% confidence interval for the primary median but does not report its limits. Precision cannot therefore be assessed from the registry record.
With enrollment of 3, any estimate would be based on a very small group. This context is relevant to how much information the study can contribute, but the record does not report the endpoint observations needed to determine what estimate was obtained. It would be inappropriate to reconstruct an estimate from enrollment alone.
How should neurological progression be understood?
The registry defines progression using clinical impression measured by Karnofsky Performance Status, radiographical response using Macdonald criteria, or cytologic response using cerebrospinal fluid cytology. In general, a composite definition that can use multiple types of evidence may capture more ways in which disease status changes. It also requires transparent rules about the timing of assessments, the interpretation of conflicting findings, and the event date. Those rules are not reported in the registry record. The endpoint's operational definition is therefore only partly described in the available information.
What can planning calculations tell readers?
Any sample-size calculations associated with the posted material are planning illustrations, not observed power and not evidence about the trial's design. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set as a fraction of the observed effect. For time-to-event illustrations, the stated quantity is a total number of events; other illustrations use participants per arm. Those assumptions do not describe this single-group trial, and the registry does not report that the trial was planned using them. Planning calculations show how a hypothetical future design might be sized under stated assumptions; they do not change the information actually observed in this study.
General statistical guidance also emphasizes that an assumed effect used for planning is not a guaranteed future effect. Planning results depend on the target effect, design, analysis method, and other assumptions. Because the primary estimate and the detailed protocol-based statistical plan are not reported in the registry record, no claim about the planning rationale, achieved precision, or planned power is supported.
Why does the design constrain inference?
Randomization can help make groups comparable at baseline, on average, while a control group provides a reference for interpreting outcomes over the same period. Neither is present as a comparison in this registered design. A single group can still contribute descriptive information, but observed outcomes alone cannot establish what would have happened to comparable patients under a different regimen. The record also reports no analyses, so no sponsor-reported comparative estimate is available to interpret. General methods cannot substitute for missing outcome results or unreported analysis details.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary outcome as survival free of neurological progression and lists overall survival as a secondary outcome. It also identifies a quality-of-life assessment and laboratory biomarker analysis among the interventions. The record does not report outcome estimates for these measures, or describe which analyses were conducted. It reports no analyses in the outcome-analysis listing.
Multiplicity arises when several outcomes, time points, subgroups, or statistical tests are considered. In general, examining many results can increase the chance that at least one appears notable by chance, unless the analysis plan addresses that issue. The registry record does not report a multiplicity adjustment, a hierarchy among outcomes, or a prespecified strategy for interpreting multiple tests. It is not possible to determine from the record whether any such approach was used.
The record does not report an analysis population, participant-level exclusions, the number included in the primary endpoint analysis, missing endpoint observations, or methods for handling missing data. These details are important because incomplete follow-up or exclusions can affect a time-to-event estimate. The listed enrollment should not be assumed to equal the number analyzed for every outcome.
Likewise, the registry record does not report an interim-analysis plan, stopping rules, or the handling of protocol deviations. The information available does not establish whether these procedures existed outside the record. Without reported analysis populations and missing-data methods, readers cannot assess whether the outcome analysis included all enrolled participants or how incomplete observations might have influenced it.
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 (Liposomal Cytarabine, High-dose Methotrexate) | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (Liposomal Cytarabine, High-dose Methotrexate) | 3 of 3 |
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 (Liposomal Cytarabine, High-dose Methotrexate) | 2 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Liposomal Cytarabine, High-dose Methotrexate) |
|---|---|---|
| Transaminitis | Hepatobiliary disorders | 2 of 3 |
| Lymphopenia | Blood and lymphatic system disorders | 1 of 3 |
The registry reports 3 participants at risk for serious adverse events and 0 with serious adverse events in the treatment group. For other adverse events, it reports 3 at risk and 2 with events. These figures are descriptive counts for the registered group, not a comparison against another treatment. The record does not provide the event terms in the listed serious-event category.
The registry also reports 3 deaths. It does not report their timing, causes, relationship to treatment, or how deaths were handled in the adverse-event summaries. The count should therefore be read as a separate recorded figure, not as evidence that the deaths were caused by treatment or were unrelated to it. The registry record does not explain whether the other-adverse-event count represents participants, events, or another reporting unit beyond the group-level fields.
With enrollment of 3, the safety counts describe only a small group. A zero count of serious adverse events in this group does not establish that such events cannot occur, and the counts do not characterize risk in a broader population. The registry record does not provide event severity, duration, or participant-level detail sufficient to interpret the clinical circumstances. These figures should be read as limited registry reporting, not as a complete safety profile.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a completed phase II, single-group study of liposomal cytarabine and high-dose methotrexate in patients with breast cancer involving the central nervous system. It records enrollment of 3 and defines neurological-progression-free survival as the primary endpoint, measured in weeks from therapy start and assessed up to 4 years. It describes several ways progression could be identified and specifies a median with a 95% confidence interval as the intended summary.
What the record does not establish is the numerical primary result. The median and its confidence interval are not reported in the registry record. Without them, readers cannot determine the observed time to progression, its precision, or how the study's endpoint experience compares with a stated benchmark. The record also does not report the endpoint's event count or analysis method.
The single-group design means the study does not provide a randomized comparison. Even if a within-group outcome estimate were available, it would not by itself show what would have occurred under an alternative treatment. The registry contains no comparative estimate that could support such an inference. It also does not report a detailed analysis plan, missing-data handling, or analysis population.
The adverse-event and death counts provide limited descriptive information. They should not be read as proof of benefit, lack of benefit, safety, or causation. In particular, the death count has no accompanying information about cause or relationship to treatment in the registry record.
The appropriate conclusion is narrow: the registry documents the study's design, intended endpoint, enrollment, and some group-level safety counts, while leaving the primary outcome result and important analysis details unreported. Neither a positive nor a negative efficacy conclusion follows from the missing endpoint estimate. This distinction matters because absence of a reported result is not equivalent to a result showing no effect.
13. Why This Trial Matters Statistically
This study illustrates why design and result reporting must be considered together. The registry describes a phase II study of a treatment combination in a serious disease setting, but registers it as single-group, with no allocation and no masking. A single group can describe outcomes in participants receiving the regimen; it cannot provide the same direct contrast as a randomized control group. That distinction remains important even when a study has a clearly defined endpoint.
The primary endpoint has a time-to-event structure and a clinical definition using clinical status, radiographical response, or cerebrospinal fluid cytology. Those features make the endpoint more informative than a simple statement that progression did or did not occur, but they also make transparent reporting of event timing, assessment rules, and analysis methods important. The registry record provides the endpoint definition and intended summary, but not the estimate or its uncertainty.
Enrollment of 3 also underscores the limited amount of information represented by the registered group. The registry's adverse-event counts are useful to distinguish what was recorded from what was not, but they do not yield a broad safety characterization. With no reported primary outcome estimate, readers cannot evaluate the study's observed endpoint experience or its precision.
Statistically, the record is a reminder that design descriptions and outcome results answer different questions. Knowing the treatment, population, endpoint, and enrollment does not supply an effect estimate. Nor can planning illustrations be treated as observed evidence or as proof that the trial had a particular design rationale. The registry record supports careful description of what was registered; conclusions beyond that require results and analysis details that are not reported.
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 primary limitation is that the registry record does not report the median survival free of neurological progression or its 95% confidence interval. It also does not report the number of primary endpoint events, individual follow-up information, censoring details, or the method used to estimate the median. As a result, the principal outcome cannot be quantitatively interpreted.
Enrollment was 3, and the study had a single group rather than a comparator arm. The design therefore cannot support a randomized estimate of the treatment combination's effect relative to another approach. The record does not give participant characteristics beyond the intended disease population, so the extent to which the enrolled group reflects the stated population cannot be assessed.
The endpoint definition allows clinical, radiographical, or cytologic evidence of neurological progression, but the record does not report rules for resolving discordant assessments or assigning event dates. It does not report assessment frequency, missing observations, analysis populations, or missing-data procedures. These omissions limit assessment of how endpoint results would have been derived, even if a numerical result were available.
The record lists overall survival as a secondary outcome and identifies quality-of-life assessment and laboratory biomarker analysis, but provides no corresponding findings. It also does not report the sample-size justification, interim analyses, detailed statistical plan, or multiplicity approach. For safety, it lists group-level counts but not event details, timing, causes of death, or treatment relationships. These are limitations of the information reported in the registry record; they should not be filled in by assumption.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Liposomal Cytarabine and High-Dose Methotrexate in Treating Patients With Central Nervous System Metastases From Breast Cancer — NCT00992602.
- Registry record last updated 2017-07-07; status last verified 2017-06.
- Results first posted 2017-07-07.
- 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
NCT00992602 is a completed phase II, single-group study sponsored by University of Washington. Its title concerns liposomal cytarabine and high-dose methotrexate for breast cancer involving the central nervous system; the official title specifies leptomeningeal metastases with or without parenchymal brain involvement. The record lists no allocation or masking and reports enrollment of 3.
The primary endpoint is survival free of neurological progression, measured in weeks from therapy start and assessed up to 4 years. Neurological progression is defined through clinical impression, radiographical response, or cerebrospinal fluid cytology. The intended summary is a median with a 95% confidence interval, but its numerical result is not reported in the registry record.
The record lists overall survival as a secondary outcome. It reports 0 serious adverse events among 3 at risk, 2 other adverse events among 3 at risk, and 3 deaths, without further context about event details or causation. No outcome analyses are listed.