Carboplatin and Temozolomide (Temodar) for Recurrent and Symptomatic Residual Brain Metastases: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Carboplatin and Temozolomide (Temodar) for Recurrent and Symptomatic Residual Brain Metastases (NCT00362817), a na phase 1, phase 2 study. The primary outcome is Affects of Response Rate of Chemotherapy With Intra-arterial Carboplatin and Oral Temozolomide.

2. Clinical Question

3. Trial Design

This was a phase I/II, multicenter, single-group trial sponsored by Ohio State University Comprehensive Cancer Center. The registry lists an enrollment of 17 and a completed status. The recorded start was 2004-10, and primary completion was 2008-01. These dates describe the registry record; they do not provide details about the timing or duration of an individual participant’s treatment or follow-up.

The only described treatment group received oral temozolomide and intra-arterial carboplatin. The arm description specifies temozolomide once a day for 5 consecutive days, as well as intra-arterial carboplatin. The record does not give the carboplatin dose, describe treatment cycles, or provide additional administration details in the arm description.

The registry identifies allocation as NA, masking as none, and the model as single group. This design does not provide a concurrent control arm for a like-for-like treatment comparison. In particular, the reference in the study purpose to patients already treated with radiation does not establish that a radiation-treated comparison group was enrolled in this trial.

The stated primary outcome was response rate by MRI criteria, measured as the percentage of patients with response up to 1 year. Listed secondary outcomes concern time to progression, overall survival, cause of death after treatment, central nervous system toxicities, and quality of life. The registry lists six outcome measures and no analyses. It does not report a statistical analysis plan, a sample-size justification, or details of how participants were included in each outcome analysis.

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 patients had received prior systemic chemotherapy for the primary tumor

Overall Study

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 Affects of Response Rate of Chemotherapy With Intra-arterial Carboplatin and Oral Temozolomide, measured over up to 1 year.

The primary endpoint is the percentage of patients with a response to chemotherapy with intra-arterial carboplatin and oral temozolomide, assessed up to 1 year. The registry says response was evaluated by MRI using the MacDonald Criteria. In its description, complete response requires disappearance of all enhancing tumor on consecutive MRI scans at least one month apart; partial response requires a >50% reduction in enhancing tumor size on consecutive MRI scans at least one month apart. Progressive disease is described as a >25% increase in enhancing tumor size on consecutive MRI scans, with stable disease applying in remaining situations.

Response rate condenses imaging assessments into a proportion of patients meeting the response definition. As a general statistical point, this can make a clinical outcome easier to summarize, but its interpretation depends on the exact response categories included in the numerator, the participants counted in the denominator, and the assessment schedule. The registry description does not specify the aggregation rule for the reported response rate, the denominator used for an analysis, or how missing or unevaluable scans were handled.

The registry record does not report an observed response count or percentage. It therefore does not establish the magnitude or precision of the response result. The criteria describe how response was to be assessed; they are not themselves evidence of an observed response.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends on the design and on how outcomes were measured and analyzed. The registry identifies this study as phase I/II, single group, with no masking and allocation listed as NA. It reports 17 enrolled participants. These descriptors establish that the registry does not describe a randomized, masked comparison between treatment groups. The record does not provide further details on the phase-specific objectives or analyses.

What does a single-group result describe?

In general, a single-group study can describe outcomes among participants who receive the intervention. For a binary endpoint such as response, the result is usually expressed as the number meeting the response definition relative to the number assessed, or as a percentage. The interpretation depends on who is counted, how the outcome is defined, and how missing assessments are treated. This registry record gives the response endpoint’s unit as the percentage of patients with response, but it does not report a response numerator or percentage, the analyzed denominator, or the missing-data rule.

A single-group result does not by itself separate treatment effects from other explanations for an outcome. General sources of uncertainty in an uncontrolled comparison can include the natural course of disease, differences in participant characteristics, and other care received. These are general considerations, not findings about this trial. The registry does not report a concurrent control group or enough information to estimate a comparative treatment effect.

How should the MRI criteria be read?

The endpoint description assigns categories according to changes in enhancing tumor size and clinical assessment. Complete response requires disappearance of all enhancing tumor on consecutive MRI scans at least one month apart; partial response requires a >50% reduction in size on consecutive scans at least one month apart. Progressive disease is defined as a >25% increase in size, and stable disease applies in the remaining situations. The registry states that response was evaluated by MRI criteria, but it does not say which categories were combined to form the response-rate numerator. Nor does it detail independent review, scan timing beyond the stated consecutive-scan requirements, or adjudication of uncertain assessments.

As a general concept, outcome definitions should be applied consistently across participants. If assessment depends on repeated imaging, the availability and timing of scans can affect whether a response category can be assigned. The record does not describe how incomplete imaging, missed visits, or unevaluable scans were handled, so their potential influence on the reported endpoint cannot be assessed.

What would an estimate and confidence interval tell a reader?

General explanation: an estimate summarizes the observed outcome in the analyzed participants, while a confidence interval expresses statistical uncertainty around that estimate under the method’s assumptions. A narrow interval generally indicates greater precision than a wide one, but precision is not the same as freedom from bias. For a single-group response percentage, an interval would not create a controlled comparison or remove limitations in outcome ascertainment.

No response estimate or confidence interval is reported in the registry record. No p-value or analysis result is listed, and the registry reports zero analyses. Consequently, there is no posted inferential result to interpret, and no basis in the registry record for assessing statistical evidence against a null hypothesis.

Why does the lack of a comparator matter?

General explanation: a concurrent comparator helps distinguish outcomes under one intervention from outcomes under an alternative condition, while random allocation can reduce systematic differences between groups. Here, the registry describes one treatment group and does not identify a concurrent control. The study purpose’s mention of patients already treated with radiation does not establish a randomized or otherwise defined comparison group. A response proportion in the treated group, even if reported, would therefore be descriptive unless additional comparative evidence and methods were available.

The record also lists no masking. In general, knowledge of treatment or study participation can influence some aspects of assessment or reporting. This does not establish that bias occurred in this trial. The registry does not state whether MRI response assessments were independently reviewed or whether assessors were otherwise unaware of participant information.

What can the adverse-event counts establish?

The registry lists zero affected among 17 participants at risk for serious events, and zero affected among 17 at risk for other events. These are counts, not a complete account of safety. General interpretation of event counts depends on the definitions of serious and other events, the observation period, the completeness of reporting, and whether events are counted by participant or by occurrence. The record does not describe those details, provide event-level terms, or report deaths in the adverse-event group data. Zero affected in the posted counts should not be read as proof that no adverse events occurred during the trial.

The record does not report the statistical methods used for the primary or secondary outcomes, any adjustment for multiplicity, interim analyses, the analysis populations, or a sample-size justification. These omissions prevent evaluation of whether analyses followed a prespecified plan or how the study’s planned precision related to its enrollment. General statistical explanations cannot substitute for those trial-specific details.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Temozolomide & Intra-Arterial (IA) Carboplatin")
n      <- c(14)
events <- c(6)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Temozolomide & Intra-Arterial (IA) Carboplatin  14  6  42.9  17.7  71.1  21.4  67.4  21.3  67.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including the primary response outcome and secondary topics covering time to progression, overall survival, cause of death, central nervous system toxicities, and quality of life. It reports zero analyses. The registry record does not describe a multiplicity strategy, such as prioritizing a limited set of hypotheses or adjusting inference when several outcomes are assessed. As a general statistical matter, examining multiple outcomes can increase the chance of at least one apparently notable result when each is tested separately; the extent and handling depend on the analysis plan, which is not reported.

The record does not report interim analyses, early-stopping rules, or a statistical analysis plan. It also does not state whether a sample-size calculation was performed or provide a justification for the enrollment of 17. The stated purpose and outcome descriptions do not establish these methods.

Analysis populations are not specified. The record does not say whether the primary analysis was intended to include every enrolled participant, only participants who received treatment, or only those with an evaluable MRI assessment. Missing-data rules are also not reported: there is no explanation of how absent scans, incomplete follow-up, withdrawal, or unevaluable assessments would affect the response calculation. These details matter because the endpoint is a percentage and therefore depends on both the response count and the denominator.

Without these methods, readers cannot determine how outcome-specific denominators were constructed, whether all enrolled participants contributed to each analysis, or how robust the planned analyses would be to missing information. These are unreported features of the registry record, not evidence that a particular method was or was not used in practice.

12. 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 0% reporting threshold.

For the treatment group, the registry lists 17 participants at risk for serious events and zero affected. It also lists 17 participants at risk for other events and zero affected. The serious-event terms list is empty. These figures indicate that no affected participants are recorded in those posted counts; they do not establish that no adverse events occurred during the trial.

As a general statistical point, event counts need context. Interpretation depends on the event definitions, the period over which participants were monitored, completeness of collection, and how events were counted. The registry record does not provide those details or list specific serious-event terms. The deaths field is not reported in the adverse-event group data, so it should not be interpreted as a count of zero deaths.

The safety figures also do not report event severity beyond the serious-versus-other grouping, timing, duration, or whether any participant discontinued treatment because of an event. Such information is not reported in the registry record. The counts are limited descriptions of the posted safety data, not a full characterization of tolerability.

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

The registry record establishes that a completed phase I/II trial enrolled 17 participants to a single group receiving oral temozolomide and intra-arterial carboplatin. It describes response as the primary outcome, assessed by MRI criteria up to 1 year, and lists several secondary outcome topics. It also posts zero affected participants among 17 at risk for serious events and zero among 17 at risk for other events.

These registry entries do not establish the trial’s response rate. The registry record does not report the number of participants with complete or partial response, the response percentage, or an uncertainty interval. It also does not report results for progression, survival, cause of death, central nervous system toxicity, or quality of life in the information summarized by the record. An endpoint definition tells readers what the study intended to measure; it is not an outcome result.

The study design also limits what can be concluded comparatively. The record identifies a single group and does not describe a concurrent control. Therefore, the registry information does not establish how outcomes compared with radiation or another treatment, and it cannot support a causal claim about differences between treatment options. The purpose statement’s reference to prior radiation does not supply a control-group result.

General statistical interpretation distinguishes an absence of a reported result from a result showing no effect. Since the primary estimate and its precision are not reported, neither the magnitude nor direction of the response outcome can be determined from this record. Likewise, the safety counts do not prove the absence of adverse events; their ascertainment details and observation period are not reported.

The appropriate reading is narrow: the registry describes the design, intended endpoints, response criteria, enrollment, and posted event counts, while leaving the principal efficacy result and key analysis methods unreported. It does not establish whether the regimen increased response, had no effect, or produced any particular level of benefit or harm.

14. Why This Trial Matters Statistically

This trial is statistically notable as a case where the registry description of a clinical question and endpoint is more complete than the posted outcome results. The study identifies response rate as its primary endpoint and specifies MRI-based criteria, yet the registry record does not report the observed response count or percentage. This distinction is important: a precisely worded endpoint does not substitute for an estimate of what happened among participants.

The record also illustrates why study design determines the kinds of conclusions an analysis can support. A single-group study can describe outcomes in the treated participants, but without a concurrent comparator it does not provide a direct treatment contrast. The registry’s mention of patients previously treated with radiation should not be mistaken for a control group. A descriptive response result, if available, would still require careful interpretation of its denominator and uncertainty.

Outcome definitions are consequential. The MRI criteria specify thresholds for response and progression and require consecutive scans for certain categories. Yet the registry does not state how the categories were combined into the response-rate numerator, how missing scans were handled, or what analysis population was used. Those choices can affect both the reported estimate and the reader’s understanding of its scope.

Finally, the posted safety counts demonstrate the limits of interpreting zero-event summaries without ascertainment details. Counts need definitions and a time frame, and they do not by themselves establish that no adverse events occurred. Taken together, these features make the record a useful reminder that endpoint definitions, design, analysis methods, outcome estimates, and reporting completeness all contribute to statistical interpretation.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The principal limitation of the registry record for interpreting efficacy is that it does not report the primary response result. There is no response count, percentage, confidence interval, or p-value. The MRI criteria are described, but the registry does not specify how response categories were combined into the response-rate numerator or identify the denominator used for analysis.

The trial is described as single group, with no masking and allocation listed as NA. No concurrent control arm is identified, so the registry does not support a direct comparison with radiation or another treatment. The statement of purpose refers to patients already treated with radiation, but the record does not establish those patients as a comparison group.

Important analysis details are not reported, including the statistical analysis plan, analysis populations, missing-data handling, multiplicity strategy, interim analyses, and sample-size justification. The registry also does not describe how MRI assessments were reviewed or how unevaluable scans were addressed. These gaps limit assessment of precision, potential bias, and the planned interpretation of outcomes.

The posted adverse-event counts lack details about definitions, observation period, ascertainment, event terms, and severity beyond the broad grouping. The deaths field is not reported in the adverse-event group data. The record lists secondary outcomes but does not report their results in the information. These limitations concern what the registry record documents; they do not establish whether additional trial information exists elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Carboplatin and Temozolomide (Temodar) for Recurrent and Symptomatic Residual Brain Metastases — NCT00362817.
• Registry record last updated 2017-06-01; status last verified 2017-05.
• Results first posted 2015-05-06.
• 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.

19. Record Summary

NCT00362817 is a completed phase I/II multicenter trial sponsored by Ohio State University Comprehensive Cancer Center. The registry records a start of 2004-10, primary completion of 2008-01, and enrollment of 17. The design is listed as single group, with allocation NA and no masking.

The treatment group received oral temozolomide and intra-arterial carboplatin. The primary outcome was response rate, expressed as the percentage of patients with response and assessed by MRI criteria up to 1 year. Listed secondary outcomes concern progression, survival, cause of death, central nervous system toxicities, and quality of life.

The registry record does not report the primary response result, outcome analyses, or key analysis methods. It lists zero affected among 17 participants at risk for serious events and zero affected among 17 at risk for other events. Those counts do not establish that no adverse events occurred.