Whole Brain Radiotherapy With or Without Temozolomide at Daily Fixed-dose for Brain Metastases Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Whole Brain Radiotherapy With or Without Temozolomide at Daily Fixed-dose for Brain Metastases Treatment (NCT01015534), a randomized phase 2 study. The primary outcome is Objective Response Rates. Assessed With Cranial MRI.

2. Clinical Question

3. Trial Design

This was a randomized, phase II, parallel-group trial comparing whole brain irradiation plus temozolomide with whole brain irradiation alone in participants with brain metastases from solid tumors. The registry record lists 55 enrolled participants. The primary outcome population is described as all enrolled participants analyzed by intention to treat. The reported arm sizes for that outcome are 28 and 27.

In the combination arm, whole brain irradiation was 30 Gy in 10 daily fractions over 2 weeks. Oral temozolomide was given 1h before each fraction, with a fixed schedule of 200 mg on Monday, Wednesday, Friday and 300 mg on Tuesday, and Thursday. The arm description says there were no adjuvant cycles of temozolomide. The comparison arm received whole brain irradiation at 30 Gy in 10 daily fractions over 2 weeks.

The registry record identifies the study as unmasked. It reports the start as 2006-01, primary completion as 2009-10, and status as completed. The sponsor is Instituto Nacional de Cancerologia de Mexico. The brief summary describes the rationale as testing whether temozolomide combined with fractionated radiotherapy could improve results compared with radiotherapy alone.

The original sample-size justification, intended statistical power, allocation ratio rationale, and details of the randomization procedure are not reported in the registry record. Further details of eligibility criteria, baseline characteristics, treatment adherence, and the handling of withdrawals are also not reported in the registry record. These omissions limit assessment of how closely the enrolled participants and the analysis reflect the intended trial population and design.

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: Seventy-two patients were assessed for eligibility. Twelve patients did not meet inclusion criteria. Five patients declined to participate. Fifty-five patients were enrolled.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Data on all enrolled participants were included in an intention-to-treat analysis.

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 Objective Response Rates. Assessed With Cranial MRI, measured over 90 days.

The primary endpoint was objective response rate assessed with cranial MRI at 90 days. It is expressed as the percentage of participants with an objective response. The registry definition counts complete response and partial response together. Complete response means disappearance of all brain metastases, assessed between two or more cranial MRI. Partial response means at least a 30% decrease in the sum of the longest diameter of brain metastases relative to the baseline sum, assessed between two or more cranial MRI.

A response endpoint gives a binary classification for each participant: an objective response was recorded or it was not. The response rate describes the proportion meeting the defined response criteria during the specified assessment period. This makes it possible to compare the frequency of responses between randomized groups. The endpoint does not by itself describe how long a response lasts, whether disease progresses later, or overall survival; those are distinct outcomes.

The registry record says the response rate is the number of participants with objective response divided by the total number of participants. It reports that all enrolled participants were included in an intention-to-treat analysis. The posted response estimates are 78.6% for whole brain irradiation plus temozolomide and 48.1% for whole brain irradiation alone. The confidence intervals are wide, so the estimates are not precise measurements of the response rates that might be expected in a larger population.

7. Results Posted in the Registry

• Whole Brain Irradiation: 48.1% (13/27) versus 78.6% (22/28) on control; risk difference -30.4 percentage points (95% CI -54.6 to -6.2), risk ratio 0.61 (0.40–0.95); unadjusted two-proportion z-test p = 0.019.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Survival Free of Brain Metastases Progression (PFS of BM)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Whole Brain Irradiation: 85.2% (23/27) versus 89.3% (25/28) on control; risk difference -4.1 percentage points (95% CI -21.7 to 13.5), risk ratio 0.95 (0.78–1.17); unadjusted two-proportion z-test p = 0.648.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Whole Brain Irradiation and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover survival free of brain metastases progression, overall survival, and adverse events. The posted results include estimates for survival free of brain metastases progression, but the registry record does not report numerical results for every listed secondary outcome. Taken together, the available secondary information does not provide a consistent set of clearly separated treatment-group results that would independently reinforce the primary response finding.

Secondary outcomes answer related but distinct questions. A response measured by cranial MRI at 90 days is not equivalent to remaining free of progression or to overall survival. The trial’s response result can therefore be interpreted on its own endpoint without assuming that it predicts the same pattern in longer-term outcomes. The secondary endpoints may add context, but they do not replace the primary endpoint or establish its durability.

Multiplicity matters because examining several outcomes creates multiple opportunities for an apparently unusual result. Unless the analysis accounts for that multiplicity, individual secondary p-values can be less persuasive than a single prespecified primary comparison. The registry record does not report whether secondary outcomes were adjusted for multiple testing, which outcomes were prioritized in the statistical plan, or whether analyses were prespecified. The secondary evidence should consequently be regarded as supportive or exploratory rather than as a set of confirmatory findings.

The overall pattern must also be read in light of the small enrolled group and the uncertainty of estimates. Lack of a clear difference on a secondary endpoint would not establish equivalence, while a nominally notable estimate would not by itself establish a reliable effect. The posted secondary information is most useful for identifying which additional outcomes were considered and what remains uncertain, rather than for extending the primary result to claims about survival or other outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Survival Free of Brain Metastases Progression (PFS of BM)
• Overall Survival
• Number of Grade 3-4 Adverse Events (AE) That Are Definitely or Probably Related to Both Groups of Treatment.

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary at the participant level: each participant either met the registry’s objective-response definition or did not. The response rate is a proportion, reported as a percentage. The registry defines objective response as complete response or partial response, using cranial MRI. A complete response is disappearance of all brain metastases, while a partial response is at least a 30% decrease in the sum of the longest diameter relative to baseline. The specified assessment time is 90 days.

Comparing response rates

A risk difference compares the response proportions by subtraction, with the direction depending on which arm is named first. The recalculated comparison is expressed as whole brain irradiation alone minus whole brain irradiation plus temozolomide. Its estimate is -0.304, and its 95% confidence interval is -0.546 to -0.062. In this orientation, a negative estimate corresponds to a lower observed response proportion in irradiation alone. The interval gives a range of effect values compatible with the posted data under the calculation method; it is not a guarantee that the true effect lies within that particular interval.

A risk ratio compares the response proportions as a ratio, while an odds ratio compares the odds of response. These measures use different scales and can have different numerical values for the same binary outcome. The recalculated odds ratio is 0.253 for irradiation alone relative to the combination arm, with a 95% confidence interval of 0.078 to 0.822. The sponsor reports an odds ratio of 3.9 for the groups in the opposite order. Comparing estimates requires attention to the arm order and which outcome is counted as the event.

Tests and uncertainty

A p-value describes how unusual results at least as different as those observed would be under a specified null model, assuming the test’s conditions hold. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of the finding. For the primary analysis, the sponsor reports a Chi-squared method, an odds ratio of 3.9, and p = 0.019. The unadjusted recalculation also gives p = 0.019. The registry record does not report whether the sponsor’s analysis was adjusted for any other variables.

A confidence interval communicates uncertainty in an estimate. A narrow interval indicates greater precision than a wide interval, conditional on the calculation and its assumptions. The primary arm-specific intervals are 63.4% to 93.8% and 29.2% to 66.9%; the risk-difference interval is also wide. This reflects that the trial has limited information for estimating the response rates and their contrast. Confidence intervals are not a substitute for examining the endpoint definition, the trial population, or possible bias.

The recalculated comparisons are simple, unadjusted calculations from the posted summary statistics. They do not account for participant-level data, covariates, or other features that may have been part of an analysis not described in the record. The registry record does not report the confidence-interval construction method for the arm-specific response rates or the recalculated contrasts. The sponsor’s reported method for the primary analysis is Chi-squared. For the secondary progression-free outcome, the sponsor reports Fisher Exact. No more detailed statistical specification is reported in the registry record.

Over-dispersion and binary outcomes

Over-dispersion is a general issue that arises when observed variation is greater than a model’s assumptions allow. In binary-response settings, heterogeneity among participants or clustering can make a simple model understate uncertainty if it is not accounted for. The registry record does not report a model for over-dispersion, clustering, or related adjustments. There is not enough information to determine whether these issues were relevant to this trial or how they were handled.

Randomization is intended to make groups comparable on average, but a small randomized trial can still have imbalances in important characteristics. Baseline data and adjusted analyses are not reported in the registry record. No conclusion about the balance of prognostic factors or the impact of adjustment can therefore be drawn from the posted summary statistics alone.

What the reported analyses establish

The primary result supports a comparison of observed objective-response proportions in the randomized groups at the specified assessment. It does not establish the mechanism of any difference, the durability of response, or an effect on overall survival. The reported secondary outcomes are analyzed separately, and the registry record does not report a multiplicity strategy. Results across several endpoints should therefore be interpreted with caution rather than as a set of independently confirmatory tests.

11. Confidence Intervals and Precision

Precision describes how tightly an estimate is determined by the observed data. The primary response rate in the combination arm is 78.6%, with a 95% confidence interval from 63.4% to 93.8%. The rate in the irradiation-alone arm is 48.1%, with a 95% confidence interval from 29.2% to 66.9%. Both intervals cover a broad range of possible response rates, so neither arm-specific estimate is highly precise.

The recalculated risk difference, expressed as irradiation alone minus the combination arm, is -0.304, with a 95% confidence interval from -0.546 to -0.062. The interval does not include zero, and the unadjusted p-value is 0.019. At the same time, the interval spans a range of effect magnitudes, from a comparatively smaller difference to a substantially larger one. Statistical evidence against no difference does not mean the effect size is known precisely.

The participant numbers are limited: 28 were included in the combination arm and 27 in the irradiation-alone arm for the primary outcome. With relatively few observations, each participant’s outcome can have noticeable influence on the estimated percentage. Larger studies may produce narrower confidence intervals if their data are otherwise comparable, though precision also depends on the true event rate and study design.

The confidence intervals quantify sampling uncertainty under their calculation assumptions. They do not capture every source of uncertainty, such as limitations in outcome assessment, incomplete follow-up, or differences between this trial population and another population. Those issues cannot be fully assessed because relevant details are not reported in the registry record. The results are best read as evidence of a higher observed response percentage in the combination arm, with substantial uncertainty about the exact size and generalizability of that difference.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not the trial’s original design assumptions. The registry record does not report the original sample-size justification. For the binary outcomes, the figures are participants per arm, not total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect.

The 80% power column gives the planned number of participants per arm for a hypothetical study to have an 80% chance of detecting the chosen effect under those assumptions, if that effect is the true one. The 90% power column gives the corresponding planning number for a 90% chance. These are design calculations, not estimates of the chance that the completed trial found a real effect. This is not observed power.

The planning rows use 100%, 75%, and 50% of the observed effect. For the primary outcome, the listed participants per arm for 80% power are 39, 66, and 139, respectively; for 90% power they are 51, 87, and 186, respectively. Smaller effects require more participants to detect under the same assumptions, which is why the planning numbers rise as the fraction of the observed effect becomes smaller.

The observed group sizes were 28 and 27 for the primary endpoint. The planning illustrations should not be interpreted as evidence that the trial was designed around those sample sizes or as a retrospective judgment about its success. The original assumptions, including the effect size chosen for design, are not reported in the registry record. These calculations are sensitive to the observed effect, which can be unstable in a small trial.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.786; treatment proportion p₁ = 0.481; average p̄ = 0.634.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6814 = 1.3355.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6465 = 0.5441.
4. n = (1.3355 + 0.5441)² / (-0.3042)² = 38.2, rounded up to 39 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.785714285714286                          # control proportion
p1 <- 0.481481481481481                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1015534)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 39 (80% power), 51 (90% power)
 75% of observed effect: n per arm = 66 (80% power), 87 (90% power)
 50% of observed effect: n per arm = 139 (80% power), 186 (90% power)
power.prop.test: 38.2 
Simulated power at n = 39 per arm: 0.812 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s primary analysis reports an odds ratio of 3.9, with a 95% confidence interval from 1.3 to 12.9 and p = 0.019, using a Chi-squared method. Its comparison is oriented as whole brain irradiation plus temozolomide relative to whole brain irradiation alone, so an odds ratio above one indicates higher odds of objective response in the combination arm under that orientation.

The recalculated analysis uses the posted response summaries and reports a risk difference of -0.304 for whole brain irradiation alone minus the combination arm, with a 95% confidence interval from -0.546 to -0.062 and an unadjusted p-value of 0.019. It also gives an odds ratio of 0.253 for irradiation alone relative to the combination arm. These odds-ratio results point in opposite numerical directions because the arm order is reversed; they describe the same directional contrast in different orientations.

The registry record indicates no discrepancy between the sponsor’s analysis and the recalculation. The sponsor’s own analysis takes precedence when describing the reported trial result. The recalculation is a simple unadjusted check based on the posted summary statistics; it is not a reconstruction of a participant-level analysis and cannot account for any analysis details absent from the record. The two approaches also report different measures of association, so the odds ratio and risk difference should not be compared by their numerical sizes.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome and secondary outcomes that include survival free of brain metastases progression, overall survival, and Grade 3-4 adverse events definitely or probably related to treatment. It reports three secondary outcomes posted and four outcome measures in total. The statistical plan for controlling the risk of false-positive findings across these outcomes is not reported in the registry record. It is also not reported whether any outcomes were designated as confirmatory or exploratory in the original analysis plan.

Multiplicity is a general concern when several hypotheses are tested. Even when each individual test uses a conventional threshold, the chance of at least one apparently significant result across a family of tests can increase as the number of tests grows. Statistical approaches can account for this, but the registry record does not describe any adjustment or testing hierarchy. The primary result is therefore best distinguished from the secondary findings, which should be interpreted cautiously in the absence of a reported multiplicity strategy.

The primary endpoint description states that all enrolled participants were included in an intention-to-treat analysis. The registry record does not report how missing MRI assessments, withdrawals, or other unavailable outcome data were handled. It does not describe imputation, sensitivity analyses, or the number of participants with missing primary endpoint data. The arm denominators reported for the endpoint do not by themselves establish whether every randomized participant had a complete assessment or how any missing observations were treated.

Details of the randomization sequence, concealment, eligibility criteria, baseline characteristics, and analysis populations beyond the primary intention-to-treat statement are not reported in the registry record. The record also does not report a full statistical analysis plan, interim analyses, or any stopping rules. These gaps limit assessment of selective outcome reporting, deviations from planned analyses, and the effect of missing data on the estimates. They do not prove that such issues occurred; they mean that they cannot be evaluated from the registry record.

16. 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 3.5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lymphopenia (39.3%), platelets (10.7%), neutrophils (3.7%), leukopenia (3.6%), nausea-vomiting (3.6%).

The registry record reports serious adverse events for 17 participants in the whole brain irradiation and temozolomide group, with 28 at risk, and for 7 participants in the whole brain irradiation group, with 27 at risk. It separately reports other adverse events for 11 participants in the combination group and 13 participants in the irradiation-alone group. These are participant counts in the posted safety record; they are not adjusted comparisons and should not be read as a complete account of event severity, timing, or causal attribution.

The listed serious adverse-event terms include Lymphopenia at 39.3%, Platelets at 10.7%, Neutrophils at 3.7%, Leukopenia at 3.6%, and Nausea-Vomiting at 3.6%. The record does not make clear in this summary how these term percentages map across groups or whether participants could contribute to more than one term. Death counts are not reported in the registry record.

The secondary outcome description refers to Grade 3-4 adverse events definitely or probably related to both groups of treatment, but the available summary does not give a complete group-specific result for that endpoint. Serious adverse events and Grade 3-4 events are not interchangeable categories. The posted safety information is therefore descriptive and incomplete for comparing the overall balance of harms between groups.

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

The posted primary results show a higher observed objective response percentage in the whole brain irradiation plus temozolomide arm than in the whole brain irradiation-alone arm at 90 days. The unadjusted comparison has p = 0.019, and the risk-difference confidence interval does not include zero. This is statistical evidence of a difference in the observed response proportions under the reported analysis, while the confidence intervals show that the magnitude remains uncertain.

The result does not establish that every participant receiving the combination would respond, or that an individual participant’s outcome can be predicted from the group-level estimates. It does not establish that a response will persist, prevent later progression, or improve overall survival. Those are separate questions, and the registry record does not report complete numerical results for all such outcomes.

The trial was randomized, which supports a comparative interpretation of outcomes between the assigned groups, but the registry record does not provide enough methodological detail to assess every potential source of bias. The primary response definition is based on MRI, and the record does not report further information about assessor masking. The study itself was unmasked. The size of the trial and the broad confidence intervals also limit precision and the ability to generalize the estimate.

These findings should be understood as results from this completed phase II trial, not as a universal estimate or a treatment recommendation. The registry record does not report a full analysis plan, complete missing-data handling, or comprehensive secondary outcome results. Those limitations matter when considering how much weight to place on the primary finding and whether it is consistent with outcomes beyond MRI response at the specified assessment.

18. Why This Trial Matters Statistically

This trial illustrates why the reported effect measure and its orientation matter. The sponsor’s odds ratio is reported for the combination arm relative to irradiation alone, while the recalculated risk difference and odds ratio are expressed for irradiation alone relative to the combination arm. Reversing the arm order changes the direction of an estimate. Careful labeling prevents a result from being misread as favoring the opposite group.

It also shows the difference between statistical evidence and precision. The primary unadjusted p-value is 0.019, but the confidence intervals around the arm-specific response rates and the risk difference remain broad. A result can meet a conventional statistical threshold while the exact magnitude of the contrast is still uncertain. Reporting the estimate with its interval gives a fuller account than reporting a p-value alone.

The trial’s size also demonstrates why observed effects should be treated cautiously when used for planning. The planning illustrations based on the observed primary effect require more participants as the targeted effect becomes smaller. Those figures are not evidence about the trial’s original design, and they are not observed power. They show how assumptions about the effect to detect shape the scale of a future study.

Finally, the record highlights the importance of a complete statistical account. Multiplicity, missing data, and analysis details affect how confidently results can be interpreted, yet several of these details are not reported. Distinguishing what the posted estimates show from what the registry record leaves unknown is central to sound statistical reading.

19. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary analysis includes 55 enrolled participants, with 28 in the combination arm and 27 in the irradiation-alone arm. These group sizes yield imprecise estimates, as reflected in the wide confidence intervals. The observed effect may not be a stable estimate of the effect that would be seen in a larger study.

The registry record does not report the original sample-size justification, the planned effect size, the intended power, or the statistical assumptions used in the trial design. It also does not report the randomization procedure, allocation concealment, eligibility details, baseline characteristics, or treatment adherence. These omissions limit assessment of trial conduct and comparability of the groups in this particular study.

Although the primary endpoint description says the analysis included all enrolled participants by intention to treat, missing endpoint data and their handling are not reported. The study was unmasked, and further information about MRI assessment procedures and assessor masking is not reported in the registry record. It is therefore not possible to assess the potential influence of missing assessments or outcome-assessment procedures from the posted summary alone.

The record does not report a complete statistical analysis plan, multiplicity adjustments, interim analyses, or stopping rules. Some secondary outcomes are listed without complete numerical results, and the safety summary does not provide a full group-specific comparison for the listed Grade 3-4 adverse-event outcome. These limitations constrain interpretation of results beyond the primary endpoint. They indicate limits in the available record, not evidence that any particular bias or protocol deviation occurred.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Whole Brain Radiotherapy With or Without Temozolomide at Daily Fixed-dose for Brain Metastases Treatment — NCT01015534.
• Registry record last updated 2013-05-08; status last verified 2013-03.
• Results first posted 2013-05-08.
• 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.

23. Record Summary

NCT01015534 is a completed randomized phase II trial of whole brain irradiation plus temozolomide compared with whole brain irradiation alone for brain metastases from solid tumors. It used a parallel design and no masking. The registry record lists 55 enrolled participants and identifies Instituto Nacional de Cancerologia de Mexico as the sponsor.

The primary outcome was objective response assessed by cranial MRI at 90 days. The posted response rates were 78.6% for the combination arm and 48.1% for irradiation alone. The sponsor reports an odds ratio of 3.9, a 95% confidence interval from 1.3 to 12.9, and p = 0.019. An unadjusted recalculation gives a risk difference of -0.304 for irradiation alone minus the combination arm, with a 95% confidence interval from -0.546 to -0.062.

The registry record also lists progression-free survival, overall survival, and adverse events as secondary outcomes. Important details about the original design assumptions, missing-data handling, multiplicity, and several secondary results are not reported in the registry record.