Cilengitide (EMD 121974) for Recurrent Glioblastoma Multiforme (Brain Tumor): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cilengitide (EMD 121974) for Recurrent Glioblastoma Multiforme (Brain Tumor) (NCT00093964), a randomized phase 2 study. The primary outcome is Percentage of Subjects With Progression-free Survival.

2. Clinical Question

This is a dose-comparison question within a study in which every arm received cilengitide. Randomization supports a comparison between the assigned dose groups, but the lack of a non-cilengitide comparison arm means the trial does not directly compare cilengitide with no cilengitide or another treatment. The record also lists overall response, time to disease progression, overall survival, one-year survival, and pharmacokinetic outcomes as secondary measures. Detailed results are posted for overall response and one-year survival; results for the other listed outcomes are not reported in the registry record.

3. Trial Design

The registry describes a completed, multicenter, open-label, randomized, parallel phase II study. The official title calls it a phase IIa trial. Participants were assigned to one of two cilengitide dose arms: 500 mg or 2000 mg. The study was uncontrolled in the sense that it had no placebo or non-cilengitide control group. Thus, its randomized comparison concerns the two doses, not cilengitide versus an alternative.

The study focused on first recurrence of glioblastoma multiforme and aimed to investigate clinical activity, safety, and tolerability. The registry lists an enrollment of 81. For the primary outcome, 40 participants were analyzed in each arm. The record's population description says the intention-to-treat population included randomized participants who had received at least 1 intravenous administration, while the number analyzed for the outcome signifies participants evaluable for it. That distinction matters when interpreting outcome denominators.

The study was open-label, meaning participants and study personnel were not masked to assigned dose according to the registry's masking designation. The primary outcome definition nevertheless specifies an independent central blinded radiology assessment of disease progression. This is a feature of outcome assessment and does not change the trial's overall open-label designation.

The record gives a study start of 2004-10-13 and a primary completion date of 2005-10-28, with status listed as completed. The record does not report the original sample-size justification, recruitment targets by arm, or detailed procedures for allocation concealment. It also does not report a full statistical analysis plan or interim-analysis procedures. Those design details should not be inferred from the randomized, parallel-group description alone.

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

Analysis population for the primary outcome, as defined in the registry: The intention-to-treat (ITT) population included all randomized subjects who had received at least 1 intravenous administration of cilengitide. Here,"Number of participants analyzed" signifies those subjects who were evaluable for this outcome measure.

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 Percentage of Subjects With Progression-free Survival, measured over Month 6.

The primary endpoint is the percentage of participants with progression-free survival at month 6. The registry defines this as surviving at least 180 days without disease progression. Progression was assessed by independent central blinded radiology assessment. The measure is therefore a binary outcome at a defined time: each evaluable participant either met the stated survival-without-progression definition or did not.

A fixed-time percentage gives a direct description of how many participants in each dose arm met the endpoint by the specified time. It is not the same as a full time-to-event analysis, which would use the timing of progression or death across follow-up. The registry lists time to disease progression and overall survival separately among the secondary outcomes, but detailed results for those measures are not reported in the registry record.

Progression-free survival is used in trials as a way to summarize whether participants remain alive without documented disease progression during a stated period. In general, this can provide information about disease control over that period, but the endpoint depends on its definition, assessment procedures, follow-up, and completeness of outcome ascertainment. The primary result should therefore be read specifically as the month-6 percentage under the registry's definition, not as a broader statement about duration of benefit or survival beyond that time.

The record describes the outcome population as randomized participants who received at least 1 intravenous administration, while the reported analyzed number refers to participants evaluable for the outcome. The registry does not report further detail about how participants lacking an evaluable month-6 assessment were handled.

7. Results Posted in the Registry

• Cilengitide 2000 mg: 15.0% (6/40) versus 7.5% (3/40) on control; risk difference 7.5 percentage points (95% CI -6.3 to 21.3), risk ratio 2.00 (0.54–7.45); unadjusted two-proportion z-test p = 0.288.

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.

Percentage of Subjects With Overall Response Rate

• 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:
  • Cilengitide 2000 mg: 12.5% (5/40) versus 5.0% (2/40) on control; risk difference 7.5 percentage points (95% CI -4.8 to 19.8), risk ratio 2.50 (0.51–12.14); unadjusted two-proportion z-test p = 0.235.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cilengitide 2000 mg and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Subjects With 1-year of Survival Rate

• 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:
  • Cilengitide 2000 mg: 37.5% (15/40) versus 22.0% (9/41) on control; risk difference 15.5 percentage points (95% CI -4.1 to 35.2), risk ratio 1.71 (0.85–3.45); unadjusted two-proportion z-test p = 0.125.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Cilengitide 2000 mg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes with detailed results in the registry are overall response and one-year survival. In both, the point estimates are higher in the 2000 mg arm than in the 500 mg arm. However, the unadjusted recalculated comparison intervals include zero, and the estimates are imprecise. This broad pattern is directionally consistent with the primary point estimates, but it does not make the primary result more conclusive or establish a dose effect.

The registry lists 14 secondary outcome measures, including time to disease progression, overall survival time, and pharmacokinetic measures. Detailed results for those other listed measures are not reported in the registry record. Consequently, the available secondary findings cannot provide a complete account of the outcomes the registry names, and no overall pattern across all listed measures can be assessed from these results alone.

In general, secondary endpoints can help describe different dimensions of a study, but multiple endpoints create multiple opportunities for apparently notable findings by chance. If many outcomes are examined, an isolated unadjusted result carries less weight unless the analysis plan and multiplicity approach are known. The registry does not report multiplicity adjustment or a prespecified hierarchy among secondary outcomes. The secondary comparisons should therefore be treated as descriptive and exploratory rather than as independent confirmation of the primary result.

The secondary outcomes also differ in meaning and timeframe. A response percentage, a one-year survival percentage, time to progression, overall survival, and plasma concentration measures are not interchangeable measures of the same event. Their interpretation depends on their definitions and assessment procedures. The record does not report detailed results for most of these listed outcomes, so their relationship to the month-6 primary endpoint cannot be evaluated from the posted results.

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

• Percentage of Subjects With Overall Response Rate
• Time to Disease Progression
• Overall Survival Time
• Percentage of Subjects With 1-year of Survival Rate
• Maximum Observed Plasma Concentration (Cmax)
• Time to Reach Maximum Plasma Concentration (Tmax)
• Area Under the Plasma Concentration-time Curve From Time Zero to Infinity After Administration (AUC 0-infinity)
• Apparent Terminal Rate Constant (Lambda z)

9. Statistical Interpretation

10. Statistical Methods Explained

The posted outcomes are percentages, and the primary endpoint is binary: a participant either met the month-6 progression-free survival definition or did not. The comparisons therefore describe proportions in two randomized dose groups. The registry reports arm-specific 95% confidence intervals and a simple unadjusted recalculation of the risk difference. It does not report a formal analysis for the outcomes; the registry lists zero reported analyses.

What does a percentage describe?

A percentage summarizes the share of participants in an analyzed group who experienced or met a defined outcome. For the primary endpoint, the event is meeting the registry's definition of progression-free survival at month 6. For response and one-year survival, the percentages refer to those distinct outcomes and timeframes. The endpoint definition and denominator must be considered together: the same percentage can have different meaning if the outcome criteria or the analyzed population differ.

The registry describes the primary population as randomized participants who had received at least 1 intravenous administration of cilengitide. It also clarifies that the number of participants analyzed signifies those evaluable for the outcome. The displayed arm counts are therefore outcome-specific analyzed counts, not necessarily a complete description of every randomized participant's follow-up.

What is a risk difference?

In general, a risk difference subtracts the event proportion in one group from the proportion in another, with the direction depending on which group is defined first. The posted comparison is for 2000 mg relative to 500 mg. Its primary risk-difference estimate is 0.075, and the 95% confidence interval runs from -0.062 to 0.212. The interval includes zero, the value corresponding to no difference on this scale. This simple unadjusted recalculation is based on the posted summary statistics rather than a reported adjusted model.

A risk difference is an absolute-scale comparison of the two proportions. It answers a different question from a ratio measure, which compares proportions relative to one another. The registry includes recalculated ratio measures in the comparison data, but the interpretation focuses on the risk difference because its zero value directly represents no difference. These recalculations do not replace an analysis specified by the study investigators; no such outcome analysis is reported in the registry record.

How should a p-value be read?

In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of a difference. The primary unadjusted recalculation gives p = 0.288. Read alongside its confidence interval, it does not establish a precise difference between doses. Because the registry reports no analysis plan or reported outcome analyses, the recalculated p-value should be understood as a simple unadjusted comparison of posted summary data.

Why are confidence intervals useful?

In general, a confidence interval expresses the uncertainty around an estimate under the method used to construct it. A 95% confidence interval is not a range that guarantees the true value lies within its particular endpoints. Rather, across repeated use of the same procedure under its assumptions, intervals constructed in this way would cover the target value at the stated rate. A wide interval indicates that the data are compatible with a broad range of values and that the estimate is not highly precise.

The arm-specific confidence intervals describe uncertainty around each percentage. The risk-difference interval describes uncertainty around the contrast between arms. These are related but not interchangeable quantities. In particular, overlapping arm-specific intervals are not a substitute for examining the interval for the direct comparison.

What does randomization contribute?

In general, random assignment is intended to make groups comparable, on average, with respect to both known and unknown baseline factors. That supports interpretation of differences between the randomized dose groups, subject to the conduct of randomization, adherence, outcome measurement, and missing data. The registry confirms randomized allocation and a parallel design but does not report allocation concealment details or a full analysis plan. Randomization does not create a no-treatment comparator where none exists, and it does not eliminate uncertainty from limited outcome counts.

The study is open-label, but the primary endpoint definition specifies independent central blinded radiology assessment. Blinding the central assessment may reduce the influence of knowledge of assigned dose on the progression assessment. It does not mean the whole trial was masked, and the record does not describe further safeguards or adjudication procedures.

What can be inferred from the posted analyses?

The simple comparisons are unadjusted recalculations from posted summary statistics. They should be read as descriptive statistical contrasts, not as a substitute for a prespecified model or a complete clinical trial analysis. The registry does not report adjusted analyses, methods for handling missing outcomes, or multiplicity procedures. Those methods are not reported in the registry record, so they cannot be assumed. The sponsor's own analysis does not take precedence in this case because the registry discrepancy indicator is false; however, the record still does not provide a reported analysis for these outcomes.

11. Confidence Intervals and Precision

The primary arm-specific percentages are 7.5% for 500 mg and 15.0% for 2000 mg. Their 95% confidence intervals are 1.6% to 20.4% and 5.7% to 29.8%, respectively. These intervals are broad relative to the point estimates, showing that the primary percentages are estimated with limited precision. They include a range of values that would imply quite different underlying rates.

For the direct comparison, the unadjusted recalculated risk difference is 0.075, with a 95% confidence interval from -0.062 to 0.212. Because this interval includes zero, the posted data are compatible with no difference as well as with differences in either direction on the risk-difference scale. The interval is more informative than the point estimate alone: it communicates both the direction of the point estimate and the substantial uncertainty around it.

In general, confidence intervals reflect both the observed data and the method used to estimate uncertainty. Limited numbers of participants or outcome events can produce imprecise estimates. The primary outcome has 40 analyzed participants in each arm, and the registry's event counts are 3 and 6. Those counts help contextualize the width of the intervals, but do not remove uncertainty. The record does not report additional model-based precision estimates.

Arm-specific intervals and a comparison interval answer different questions. The first pair quantifies uncertainty around each arm's percentage; the risk-difference interval quantifies uncertainty around the difference. Readers should focus on the direct comparison interval when considering how precisely the dose groups differ. The registry does not report a multiplicity-adjusted confidence interval or a prespecified inferential analysis.

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 sample-size figures are planning illustrations based on the observed effect, not the original trial's design calculation. The 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 original trial's own sample-size assumptions and justification are not reported in the registry record.

For the binary outcomes in this trial, the planning entries are participants per arm, not total events. A row planning for 100% of the observed effect uses the full observed contrast as the target for the illustration; the 75% and 50% rows use smaller target effects. The primary outcome illustration gives 278 participants per arm for 80% power and 371 participants per arm for 90% power when planning for 100% of the observed effect. These are planning quantities, not observed trial counts.

In general, power is the chance that a specified statistical test will detect an effect of the chosen size under the assumptions used for the calculation. The 80% power column gives the participants per arm estimated for an 80% chance of detecting the target effect if that effect and the planning assumptions were correct. The 90% column uses a higher chance of detection and therefore calls for a larger planned sample under the same setting. The calculations are not evidence that the completed trial had either level of power.

Smaller effects are harder to distinguish from random variation, so the planning illustrations require more participants per arm when the target is a smaller fraction of the observed effect. This is a general relationship in sample-size planning, not a conclusion about the actual probability that this trial detected an effect. The figures are not observed power.

The trial's actual enrollment was 81. That number is distinct from every planning illustration, which is based on stated hypothetical assumptions and an effect derived from the posted results. Time-to-event calculations, if presented elsewhere, would be expressed as total events according to the planning description; these binary-outcome figures are per arm.

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 = 0.075; treatment proportion p₁ = 0.150; average p̄ = 0.112.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4469 = 0.8758.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4437 = 0.3734.
4. n = (0.8758 + 0.3734)² / (0.0750)² = 277.5, rounded up to 278 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 <- 0.075                          # control proportion
p1 <- 0.15                          # 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(93964)
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 = 278 (80% power), 371 (90% power)
 75% of observed effect: n per arm = 458 (80% power), 613 (90% power)
 50% of observed effect: n per arm = 948 (80% power), 1,268 (90% power)
power.prop.test: 277.5 
Simulated power at n = 278 per arm: 0.808 (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. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures and 14 secondary outcome measures. It reports zero analyses. The detailed outcome data include the primary endpoint and two secondary endpoints, with simple unadjusted recalculations available for the comparisons. The registry does not report a multiplicity strategy, such as adjustment of significance thresholds or a hierarchy determining which outcomes were confirmatory. Without that information, the secondary results should not be interpreted as if they were protected from the increased chance of chance findings that can accompany multiple comparisons.

The primary outcome population is described as randomized participants who received at least 1 intravenous administration of cilengitide. The registry also states that the number analyzed for the outcome signifies participants evaluable for it. These descriptions identify a population and an evaluability rule, but they do not explain the handling of participants without an evaluable outcome. The methods for missing data, withdrawals, censoring, or imputation are not reported in the registry record.

The total enrollment was 81, while 40 participants per arm were analyzed for the primary outcome. The one-year survival outcome has 41 participants analyzed in the 500 mg arm and 40 in the 2000 mg arm. Safety denominators also differ by group and outcome category. These denominators should be read as measure-specific; the record does not give enough information to reconcile every difference or to determine the effect of missing information on each estimate.

In general, missing outcomes can affect percentages if participants with unavailable measurements differ systematically from those with evaluable data. This is a general concern, not evidence that such a pattern occurred in this study. The registry does not report sensitivity analyses that would show how results change under alternative assumptions about missing outcomes.

The record also does not report an interim-analysis plan, stopping rules, or a complete statistical analysis plan. Those procedures must not be inferred from the fact that the study was randomized or from the posted p-values. Their absence from the registry record limits assessment of how the analyses relate to the trial's original statistical objectives.

15. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: convulsion (20.0%), headache (12.2%), aphasia (7.5%), pulmonary embolism (7.5%), deep vein thrombosis (5.0%).

The registry reports serious adverse events in 16 of 41 participants at risk in the 500 mg group and 18 of 40 at risk in the 2000 mg group. For other adverse events, the corresponding figures are 41 of 41 and 39 of 40. These are counts and denominators for the registry's adverse-event categories; they should not be combined or treated as measures of treatment effect.

The registry's listed serious adverse-event terms include convulsion at 20.0%, headache at 12.2%, aphasia at 7.5%, pulmonary embolism at 7.5%, deep vein thrombosis at 5.0%, and asthenia at 4.9%. The record does not specify in these figures how each term is distributed between dose arms, so they should not be assigned to a particular arm. Death counts are not reported in the registry record.

In general, adverse-event counts describe events recorded during the study and need context about definitions, follow-up, severity, and attribution. These registry figures do not by themselves establish whether an event was caused by the study drug, and they do not provide a comparison with an untreated or alternative-treatment group. The registry record does not report additional detail about event ascertainment or causal assessment.

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

The posted results describe progression-free survival percentages at month 6 in two randomized cilengitide dose groups. The 2000 mg arm has a higher point estimate than the 500 mg arm, but the primary risk-difference confidence interval includes zero and is broad. The data therefore leave substantial uncertainty about the size and direction of the difference between doses.

This finding is not equivalent to evidence that either dose improves outcomes compared with no cilengitide or another treatment. The trial was uncontrolled: both arms received cilengitide, and randomization addressed the comparison between those two doses. A dose comparison cannot answer the separate question of what outcomes would have occurred in a non-cilengitide group.

The secondary endpoint estimates also have substantial uncertainty, and the registry does not report detailed results for most listed secondary measures. Multiple outcomes without a reported multiplicity plan provide less secure evidence than a single prespecified comparison. The registry reports no analyses and does not provide the full statistical analysis plan, so the posted recalculations should not be mistaken for a complete account of the investigators' intended analyses.

In general, a trial result is most informative when read with the endpoint definition, analyzed population, comparator, and precision together. Here, the primary endpoint is a fixed-time binary measure based on survival without progression, and its analyzed count is the number evaluable for that outcome. The registry does not report the missing-data methods or enough detail to establish how unevaluable outcomes affect interpretation.

The numerical results are descriptive evidence from this trial record. They do not alone establish a definitive dose difference, an effect relative to no treatment, or a broader clinical conclusion. The confidence intervals and the design limitations are central to interpreting what the posted estimates can support.

17. Why This Trial Matters Statistically

This trial illustrates why a point estimate should not be read in isolation. The month-6 percentages are different between the dose groups, but the direct comparison has a broad confidence interval that includes zero. The point estimate alone gives an incomplete picture; precision and the range of values compatible with the data are essential to interpretation.

It also shows how comparator choice defines the question a randomized trial can answer. Randomization permits a dose-group comparison, while the absence of a non-cilengitide arm prevents a direct estimate against no cilengitide or another treatment. The word randomized does not by itself imply that every clinically relevant comparison is available.

The registry distinguishes the population eligible for the primary endpoint from the number evaluable for it. That distinction is useful when reading trial percentages: the denominator is part of the result, and differences between enrollment, analysis populations, and outcome-specific evaluability can matter. The registry's limited reporting of missing-data methods makes that distinction especially important.

Finally, the record lists many outcomes but reports no analyses and does not give a multiplicity plan. This is a practical example of why secondary findings should be interpreted cautiously when the analysis hierarchy is unavailable. The study's posted data can be described and compared, but the missing design and analysis details constrain the strength of statistical conclusions.

18. 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.

Several limitations specific to this trial shape interpretation. First, the study was open-label. The primary progression assessment was described as independent, central, and blinded, but the record does not describe other masking or assessment safeguards. The open-label designation remains relevant when considering outcomes beyond that central radiology assessment.

Second, the trial was uncontrolled and compared two doses of cilengitide. It cannot directly estimate outcomes against placebo, no treatment, or another therapy. The primary comparison is therefore limited to the two randomized dose groups.

Third, the primary endpoint results come from 40 analyzed participants per arm, with event counts of 3 and 6. The confidence intervals are broad, and the direct comparison interval includes zero. The study's enrollment was 81, but the registry does not explain all differences between enrollment and outcome-specific analyzed counts or report missing-data methods.

Fourth, the record lists 15 outcome measures but reports no analyses. Detailed results are posted for only two secondary outcomes, while results for the other listed outcomes are not reported in the registry record. A multiplicity approach and the original statistical analysis plan are also not reported, limiting assessment of which findings were intended as confirmatory.

Finally, the record does not report the original sample-size justification, allocation-concealment procedures, interim analyses, or analysis methods for missing outcomes. These omissions do not establish that particular procedures were absent from the trial; they mean those procedures cannot be evaluated from the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Cilengitide (EMD 121974) for Recurrent Glioblastoma Multiforme (Brain Tumor) — NCT00093964.
• Registry record last updated 2019-04-16; status last verified 2019-01.
• Results first posted 2019-04-16.
• 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.

22. Record Summary

This completed, multicenter, open-label, randomized parallel phase II study evaluated single-agent cilengitide at 500 mg and 2000 mg for first recurrence of glioblastoma multiforme. The registry lists enrollment of 81 and identifies progression-free survival at month 6 as the primary outcome. The primary outcome was defined as surviving at least 180 days without progression, assessed by independent central blinded radiology review.

The posted primary percentages were 7.5% for 500 mg and 15.0% for 2000 mg. The unadjusted recalculated risk difference was 0.075, with a 95% confidence interval from -0.062 to 0.212. Overall response and one-year survival are also reported as secondary outcomes, while results for most listed secondary measures are not reported in the registry record. The record provides no reported analyses, multiplicity plan, or detailed missing-data methods.