Temozolomide and Vinorelbine in Treating Patients With Recurrent Brain Metastases: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Temozolomide and Vinorelbine in Treating Patients With Recurrent Brain Metastases (NCT00026494), a na phase 1, phase 2 study. The primary outcome is Radiographic Response Assessed by Macdonald Criteria Every 2 Months.

2. Clinical Question

The central question is whether radiographic response was observed during treatment in this group of patients with recurrent brain metastases. The endpoint description says tumor measurements were recorded at baseline and at each MRI scan, with lesions measured in two dimensions. That identifies the type of observation planned; it does not provide the criteria details needed to independently determine how response was classified.

The study record describes a combination regimen and a single-group design, not a comparison of the combination against another treatment or against no treatment. Consequently, the registry record cannot answer a comparative-effectiveness question from the primary endpoint information available. It also does not report response counts by treatment phase or vinorelbine dose level. The clinical question is therefore narrower than whether the regimen is better than an alternative: it concerns the recorded radiographic response measure in the enrolled study group, for which the posted registry record gives no outcome result.

3. Trial Design

This is a phase I/II, completed, single-group trial sponsored by Memorial Sloan Kettering Cancer Center. The registry record lists enrollment of 49 and a start date of 2001-07, with primary completion at 2008-04. Allocation is listed as not applicable and masking as none. The record does not report a randomized control group, and the dose-level groups in the safety summary are not a like-for-like control comparison.

The intervention is temozolomide with vinorelbine. The listed regimen administers vinorelbine on days 1 and 8 of each cycle and temozolomide on days 1 to 7 and 15 to 21, at 150 mg/m2/day. A cycle is defined as 28 days. Safety summaries are organized under vinorelbine dose labels of 15mg/m2, 20mg/m2, 25mg/m2, and 30mg/m2. The record does not give a participant flow or explain how enrollment was distributed across phases or dose levels. It also does not say whether participants received other treatments during follow-up.

The primary outcome is a participant count for radiographic response assessed by Macdonald Criteria every 2 months, with a stated timeframe of 2 years. The outcome description specifies baseline and MRI tumor measurements, including measurement of lesions in two dimensions. The registry record lists one outcome measure and zero analyses. It does not include a primary response count, a response estimate, or an analysis population. It also does not report a sample-size justification, detailed statistical plan, or protocol-level explanation of the phase transitions. Accordingly, the design can be described from its registry entries, but its rationale and analysis conduct cannot be reconstructed beyond those entries.

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

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Radiographic Response Assessed by Macdonald Criteria Every 2 Months, measured over 2 years.

The primary endpoint is the number of participants with radiographic response assessed by Macdonald Criteria every 2 months, over a timeframe of 2 years. Tumor measurements were to be recorded at baseline and at each MRI scan, and the description says lesions must be measured in two dimensions. The endpoint parameter is a participant count rather than a time-to-event measure or a continuous change in tumor size.

In general, a radiographic response endpoint is used to describe whether tumors meet prespecified imaging criteria for response during an observation period. Repeated imaging can track tumor measurements over time, while baseline measurements provide a reference for later assessment. The registry record names the Macdonald Criteria but does not provide the operational response definitions, confirmation rules, or handling of unevaluable scans. Those details are needed to reproduce the classification from measurements alone.

The record does not report how many participants met the response criteria, how many were assessed, or what summary estimate was calculated. Thus the endpoint’s intended measurement is identifiable, but its observed result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry entries describe a phase I/II, single-group study and list one primary outcome measure with zero analyses. They do not identify a statistical analysis plan, a model, a hypothesis test, or a method for estimating uncertainty for the response outcome. The explanations below distinguish the general statistical ideas relevant to this design from methods documented for this trial.

What does a participant-count endpoint represent?

The primary measure is a count of participants with radiographic response. In general, a binary outcome classifies each participant into one of two states for the endpoint, such as meeting or not meeting a stated response definition. A count can describe how many participants meet the definition, but interpretation usually also requires the number assessed and a clear rule for missing or unevaluable assessments. The registry record does not report the response count, assessed denominator, or these classification rules.

When such a count is reported, a response proportion is often used to express the count relative to the analysis population. That proportion is not available for this trial, and none can be inferred from the enrollment total. The number enrolled does not establish how many were eligible for the analysis, received treatment, completed imaging, or had an evaluable assessment.

What would uncertainty measures add?

In general, a confidence interval gives a range of values compatible with the observed data under the interval’s statistical assumptions. It helps readers assess the precision of an estimate; a point estimate alone does not convey that uncertainty. For a binary response measure, an interval would ordinarily be considered alongside the response count and analysis denominator. No response estimate or confidence interval is reported in the registry record, so the precision of the intended endpoint cannot be assessed.

A p-value, when used, addresses compatibility between data and a specified statistical null hypothesis under the assumptions of a test. It does not show the size or clinical importance of an outcome, and it does not replace an estimate with an uncertainty interval. The registry does not report a primary endpoint test, null hypothesis, or p-value. No test should be presumed from the existence of an endpoint.

How does the single-group design affect inference?

In a single-group design, the study can describe outcomes observed among participants in the group, if the results are reported. It does not provide a concurrent control outcome for estimating a between-group contrast. In general, without a control group, observed changes or responses cannot be separated from all other explanations by a randomized comparison. The registry explicitly lists no allocation and a single-group model, so the dose-level safety categories should not be interpreted as randomized arms or as a controlled comparison.

The safety summary has vinorelbine dose labels and different numbers at risk. In general, unequal group sizes and differences in who entered each dose group can complicate comparisons. The record does not report a statistical comparison across these dose labels, or enough design details to interpret them as comparable cohorts. Counts by label are therefore best treated as descriptive registry summaries.

What is the role of measurement timing?

Repeated MRI measurements were planned every 2 months, with a stated timeframe of 2 years. In general, repeated assessments allow response status to be considered over an observation period, but interpretation depends on how visits outside the schedule, incomplete follow-up, and changes in measurements are handled. The record says measurements were taken at baseline and at each MRI scan and that lesions must be measured in two dimensions. It does not report visit windows, confirmation requirements, independent review, or rules for handling missed scans.

Macdonald Criteria are named as the assessment standard. The registry description does not reproduce the complete criteria or explain who applied them. The criteria name alone is not enough to reconstruct each participant’s response classification. No response-by-time results are posted, so the impact of repeated measurement on the reported endpoint cannot be evaluated.

What do the planning assumptions mean?

The registry record describes a planning illustration using the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. For time-to-event tables, the stated planning quantity is total events; for other outcomes, it is participants per arm. These are planning assumptions, not descriptions of the actual single-group trial design. No numerical planning estimates or observed effect are reported in the registry record. The illustration therefore does not supply an observed-power result or a basis for concluding that the study had adequate power for its primary endpoint.

Overall, the record supports a description of the endpoint, schedule, and broad design, but not a reconstruction of the statistical analysis. The analysis population, missing-data approach, response estimate, uncertainty measure, and inferential test are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and zero analyses. It identifies radiographic response as the primary measure, but it does not report how that measure was analyzed. A multiplicity plan is not reported in the registry record. In general, multiplicity concerns arise when several outcomes, time points, subgroups, or statistical tests are considered; the chance of a false-positive finding can increase if many tests are interpreted without an appropriate plan. The record does not state whether additional outcomes or comparisons were prespecified outside the posted registry entries, so no adjustment strategy can be inferred.

Missing-data handling is not reported in the registry record. The endpoint description refers to baseline measurements and MRI scans every 2 months, but does not state how missed scans, withdrawals, deaths, incomplete measurements, or unevaluable images were handled. Nor does it report the number of participants with an endpoint assessment. As a result, the enrollment total of 49 cannot be assumed to be the primary analysis denominator.

The analysis population is not reported in the registry record. It does not say whether the endpoint was assessed among all enrolled participants, those who began treatment, those with follow-up imaging, or another group. The treatment schedule and the safety denominators do not resolve this question. These omissions limit reproducibility and make it difficult to judge whether missing observations could have affected the response result.

The registry record also does not report interim analyses, stopping rules, or a detailed prespecified statistical plan. Their absence from the record is not evidence about whether such procedures were part of other study documents; they are simply not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: platelets (50.0%), neutrophils (25.0%), leukocytes (25.0%), lymphopenia (25.0%), seizure (25.0%).

The safety summaries are grouped by vinorelbine dose label. For serious adverse events, the registry lists 4 affected participants among 7 at risk in the 15mg/m2 group, 4 among 4 in the 20mg/m2 group, 8 among 22 in the 25mg/m2 group, and 9 among 16 in the 30mg/m2 group. For other adverse events, the corresponding affected and at-risk counts are 7 and 7, 4 and 4, 19 and 22, and 16 and 16.

These are descriptive counts, not a randomized comparison. The numbers at risk differ across dose labels, and the registry record does not report that participants were randomly assigned among these groups. The counts should not be interpreted as establishing that one dose label caused more or fewer events than another. The record does not describe event-collection procedures or the analysis population in detail.

The listed serious-event terms include Platelets at 50.0%, and Neutrophils, Leukocytes, Lymphopenia, Seizure, and Syncope at 25.0% each. The registry record does not specify the denominator or calculation details for these term percentages. Deaths are not reported in the registry record. These summaries do not replace a full account of event timing, severity grading, attribution, or participant-level overlap.

12. What the Result Does, and Does Not, Mean

The record establishes that a phase I/II single-group trial evaluated a temozolomide and vinorelbine regimen in patients with recurrent brain metastases, and that radiographic response was the stated primary endpoint. It also gives a treatment schedule, a two-year endpoint timeframe, and descriptive safety counts by vinorelbine dose label. Those details describe the study’s intended question and some posted safety information.

The registry record does not report the primary response count or an analysis of that outcome. Therefore, it does not show how many participants met the response criteria, what proportion of an analysis population responded, or how precise any response estimate might be. The absence of a posted result does not mean that no response occurred, and it does not establish that the regimen was effective or ineffective. It means that the main outcome cannot be interpreted from the registry record.

The single-group design also limits what a reported response result could establish. In general, a response observed in a treated group is not equivalent to a controlled estimate of what treatment changes compared with an alternative. Since no concurrent comparator is listed, a causal comparative conclusion cannot be drawn from the design described in the registry.

The safety counts document affected participants in the registry’s dose-labeled groups, but they are not sufficient by themselves to establish comparative safety across doses or to characterize the overall balance of benefits and harms. The record does not provide full event definitions, analysis populations, or deaths. Nor does it report enough statistical detail to assess missingness or precision.

Accordingly, the statistical meaning is limited: the registry states a response question and gives some safety counts, but leaves the primary response result and its uncertainty unreported. Readers should distinguish that reporting limitation from a finding of no response or no effect.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly named endpoint is not the same as a reported endpoint result. The registry identifies radiographic response, an assessment schedule, and a timeframe, but does not include the response count or its analysis. Without those results, readers cannot assess the magnitude or precision of the primary outcome, regardless of how clearly the endpoint is described.

It also illustrates the inferential limits of a single-group design. If a response result were available, it could describe what was observed among the analyzed participants. The lack of a concurrent comparison group would still prevent a direct randomized estimate of how outcomes differed from an alternative. A study can therefore be informative about its participants while remaining limited for comparative claims.

The safety summaries highlight another statistical distinction: counts are tied to denominators, and the denominators differ across the vinorelbine dose labels. Such summaries are useful as descriptive records, but they do not by themselves establish a dose-response relationship. Design details and appropriate comparative analyses would be needed for that interpretation, and those are not reported in the registry record.

Finally, the stated planning assumptions are not the same as trial results or a justification of the actual study size. The record does not report the observed primary effect, numerical planning estimates, or a sample-size justification. This distinction matters because planning illustrations cannot substitute for an observed outcome estimate, and they do not establish observed power. The trial is statistically noteworthy as a case where design, endpoint, and analysis reporting need to be considered separately.

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 important limitation for interpreting the primary endpoint is that no response result or analysis is reported in the registry record. Although enrollment is listed as 49, the record does not identify how many participants had evaluable imaging, the analysis denominator, or the response classification count. Thus the endpoint’s observed magnitude and precision cannot be assessed.

The design is single group, with allocation listed as not applicable and masking as none. No concurrent control group is reported, so a comparative treatment effect cannot be estimated from the design described. Safety groups labeled by vinorelbine dose are not a substitute for a randomized comparator, and the registry does not provide enough detail to establish that they are directly comparable.

The endpoint description lacks operational detail beyond naming Macdonald Criteria, specifying two-dimensional lesion measurements, and describing MRI assessments every 2 months over 2 years. Response rules, confirmation requirements, image-review procedures, visit windows, and handling of incomplete or unevaluable scans are not reported. The analysis population, missing-data approach, and participant flow are also not reported.

Other limitations of the registry record include the absence of a statistical analysis plan, multiplicity strategy, interim-analysis information, and sample-size justification. The safety information does not include deaths, event attribution, collection methods, or detailed severity and timing information. The listed term percentages lack a reported denominator or calculation detail. These gaps constrain reproducibility and limit the conclusions that can be drawn from the posted record; they should not be mistaken for evidence that the unreported procedures or outcomes did not exist.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Temozolomide and Vinorelbine in Treating Patients With Recurrent Brain Metastases — NCT00026494.
• Registry record last updated 2016-01-18; status last verified 2015-12.
• Results first posted 2016-01-18.
• 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.

18. Record Summary

NCT00026494 is a completed phase I/II, single-group trial sponsored by Memorial Sloan Kettering Cancer Center. It enrolled 49 participants with recurrent brain metastases and studied temozolomide with vinorelbine. The listed schedule gives vinorelbine on days 1 and 8 and temozolomide at 150 mg/m2/day on days 1 to 7 and 15 to 21 of each 28-day cycle.

The stated primary endpoint is the number of participants with radiographic response assessed by Macdonald Criteria every 2 months over 2 years. Tumor measurements were to be recorded at baseline and at MRI scans, with lesions measured in two dimensions. The response result and analysis are not reported in the registry record. Safety counts are listed by vinorelbine dose label; deaths are not reported. The analysis population, missing-data approach, and detailed statistical plan are not reported in the registry record.