Ramucirumab or Anti-PDGFR Alpha Monoclonal Antibody IMC-3G3 in Treating Patients With Recurrent Glioblastoma Multiforme: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ramucirumab or Anti-PDGFR Alpha Monoclonal Antibody IMC-3G3 in Treating Patients With Recurrent Glioblastoma Multiforme (NCT00895180), a non-randomized phase 2 study. The primary outcome is Percentage of Participants Who Achieved Progression-Free Survival Rate at 6 Months (PFS-6).

2. Clinical Question

This phase 2 study examined two biological treatments in recurrent glioblastoma multiforme. Its stated purpose was to evaluate safety and efficacy. The primary endpoint focused on whether participants remained alive without progression through the specified 6-month period. Secondary outcomes included treatment-emergent adverse events, objective response, overall survival, pharmacokinetic and pharmacodynamic measures, and anti-drug antibodies. The registry record describes these questions, but does not report results for the primary endpoint or the listed secondary outcomes. The non-randomized design also means that any differences between the groups would require cautious interpretation: the record does not establish that the groups were comparable at baseline or that treatment allocation was independent of participant characteristics.

3. Trial Design

This was an open-label, phase 2, parallel-group study with non-randomized allocation and no masking. The registry lists an enrollment of 80 and two groups: ramucirumab and olaratumab. The sponsor was Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. The study started in 2010-07, had a primary completion date of 2012-06-22, and is recorded as completed.

According to the arm descriptions, ramucirumab was administered intravenously over 1 hour on day 1, with courses repeating every 14 days in the absence of progression or unacceptable toxicity. Olaratumab was administered intravenously over 60–90 minutes on day 1, also repeating every 14 days unless progression or unacceptable toxicity occurred. Dose amounts and further treatment details are not reported in the registry record.

Non-randomized allocation means the registry does not describe chance assignment to the two groups. Without randomization, participant characteristics, clinical circumstances, or other factors may differ between arms and may also relate to outcomes. The open-label design means masking was absent; the record does not describe any blinded outcome assessment. These design features matter when interpreting a comparison, particularly for outcomes that involve clinical judgment.

The enrollment figure is a study-level figure, not a reported outcome denominator for every analysis. For the primary endpoint, the stated population includes enrolled participants who received at least one dose of study drug. The record does not provide a participant flow account, baseline characteristics, or analysis-specific denominators. It also does not report the protocol’s allocation procedure, sample-size justification, interim analyses, or a detailed statistical analysis plan.

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: The completers include those participants with progressive disease (PD) or those who died.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All enrolled participants who received at least one dose of study drug.

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 Participants Who Achieved Progression-Free Survival Rate at 6 Months (PFS-6), measured over Start of treatment to PD or Death Up To 6 Months.

The primary endpoint is the percentage of participants who achieved progression-free survival at 6 months (PFS-6). Progression-free survival is defined from the start of treatment to the earliest date of tumor progression or death from any cause. The stated timeframe is from treatment start to progression or death up to 6 months. The population is all enrolled participants who received at least one dose of study drug.

Progression was defined using modified Response Assessment in Neuro-Oncology Group criteria through the American Society of Clinical Oncology. The listed criteria include a 25% or greater increase in the sum of the products of perpendicular diameters of enhancing lesions, any new lesion, or clinical deterioration. The description identifies RANO as standardized response criteria based on bi-dimensional measurements of the largest contrast-enhancing area.

As a general statistical concept, a fixed-time progression-free survival percentage describes the proportion meeting a specified status by a chosen time point. It is clinically interpretable as a milestone outcome, but it compresses the timing of events into a single time point: participants who progress earlier and later are both counted according to whether they meet the endpoint at the milestone. The registry record does not report the PFS-6 percentages, their uncertainty, or the event and censoring details used to derive them. Therefore, the endpoint definition can be described, but its observed value and precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage endpoint represent?

For a binary outcome such as achieving PFS-6, each participant is classified according to whether the endpoint was met. The group percentage summarizes the proportion classified as meeting it. This is different from describing the length of time each participant remained progression-free: the milestone percentage focuses on status by a fixed time, whereas a time-to-event analysis uses event timing and may account for participants whose follow-up ends before an event is observed.

As a general statistical concept, an estimated proportion is subject to sampling uncertainty. A confidence interval gives a range of values compatible with the data under the method used and conveys how imprecisely the proportion is estimated. It is not a guarantee that the true value lies in the interval. The registry record does not report the PFS-6 estimate or an interval, so neither the magnitude nor precision of that primary result can be evaluated.

Why does allocation matter?

Random allocation is commonly used to balance measured and unmeasured prognostic factors between groups, on average. This study is recorded as non-randomized, so that protection does not apply. If treatment groups differ in factors related to progression or death, an observed difference could be confounded. Adjustment methods can sometimes address measured differences, but they cannot automatically remove bias from unmeasured factors. The record does not report baseline comparisons, covariate adjustment, or a causal analysis plan.

The parallel-group structure means participants were described in one of two treatment arms, rather than receiving both treatments in sequence. However, the parallel structure alone does not make the groups comparable. The registry explicitly cautions that the arms are not a like-for-like control comparison. Interpretation should therefore focus on descriptive outcomes unless stronger analytic details are available.

How should the planned sample-size illustrations be read?

The sample-size assumptions describe planning illustrations computed from the observed effect, not the study’s original design. They assume a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. Each illustration varies the effect to detect as a stated fraction of the observed effect. For non-time-to-event outcomes, the stated convention is participants per arm for 80% power or another listed power level; time-to-event calculations use a total number of events.

These are hypothetical planning quantities, not observed power and not evidence that the original study was adequately or inadequately sized. The registry record does not report the original sample-size justification. Because the primary effect estimate is not reported, no actual effect magnitude can be inferred from the planning description. Planning calculations based on an observed effect are also conditional on that estimate, which may itself be uncertain. They should not be treated as a prospective design rationale or as a substitute for the study’s observed results.

What can significance testing establish?

In general, a hypothesis test evaluates how compatible observed data are with a specified null hypothesis under stated assumptions. A p-value is not the probability that the null hypothesis is true, nor does it measure clinical importance. A confidence interval is often more informative about plausible effect sizes and precision. Neither a p-value nor an interval for the primary comparison is reported in the registry record.

The record gives no detailed statistical plan for endpoint calculation, handling of censoring, covariate adjustment, or choice of test. It is therefore not possible to verify the analysis approach or assess whether it matched a prespecified plan. The simple planning assumptions do not supply these missing details.

How should multiple outcomes be considered?

The registry lists several secondary outcomes in addition to the primary endpoint. When many outcomes are examined, the chance of at least one apparently notable finding can increase if results are interpreted without accounting for multiplicity. Statistical approaches may control error rates or prioritize outcomes, but the registry record does not report a multiplicity strategy. The outcomes should therefore be treated as separate stated questions, not as a set of confirmed findings.

Similarly, the record does not provide enough information to determine whether analyses were prespecified, whether interim analyses occurred, or how missing outcome data were handled. These are important elements of statistical interpretation. Their absence means uncertainty about the analysis process remains; it does not establish that a particular method was or was not used outside the registry record.

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("Group 1 Ramucirumab", "Group 2 Olaratumab")
n      <- c(40, 40)
events <- c(5, 3)
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  Group 1 Ramucirumab  40  5  12.5  4.2  26.8  5.5  26.1  5.6  26.2
ARM  Group 2 Olaratumab  40  3  7.5  1.6  20.4  2.6  19.9  2.7  19.9

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies PFS-6 as the primary outcome and lists multiple secondary outcomes: treatment-emergent adverse events, objective response, overall survival, pharmacokinetic measures for each treatment, pharmacodynamic profiles, and anti-drug antibodies for each treatment. Examining multiple outcomes raises a multiplicity question. As a general statistical principle, if many hypotheses are tested, interpreting any isolated result as definitive can overstate the evidence unless the analysis plan accounts for the number and hierarchy of tests. The registry record does not report a multiplicity adjustment or a hierarchy for secondary outcomes.

The record lists 0 analyses, and does not give numerical primary or secondary outcome results. It does not report whether analyses were conducted, whether they were prespecified, or whether results were submitted elsewhere. No missing-data method, censoring rules beyond the endpoint definition, or sensitivity analysis is reported in the registry record.

The stated primary population consists of all enrolled participants who received at least one dose of study drug. This definition does not clarify how participants who enrolled but received no dose were handled in the primary analysis, nor does it provide the number included in each arm’s endpoint analysis. The enrollment figure alone cannot establish the analysis denominators. The record also does not report withdrawals, follow-up completeness, or reasons for missing endpoint assessments. These omissions prevent assessment of how missing data might affect the primary estimate.

These gaps do not show that missing observations or multiplicity problems changed the study findings. They mean that the registry information is insufficient to evaluate those possibilities or to reproduce the analyses.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dehydration (7.5%), neoplasm progression (7.5%), convulsion (7.5%), deep vein thrombosis (7.5%), incorrect storage of drug (5.0%).

The registry’s serious-event summary records 13 of 40 participants in the ramucirumab group and 14 of 40 in the olaratumab group in the serious-event affected fields. The other-event affected fields record 38 of 40 and 39 of 40, respectively. These figures describe the posted counts within each group. They are not a randomized comparison, and the record does not report a statistical test or an adjusted safety analysis.

The listed serious-event terms and percentages are dehydration, 7.5%; neoplasm progression, 7.5%; convulsion, 7.5%; deep vein thrombosis, 7.5%; incorrect storage of drug, 5.0%; and medication error, 5.0%. These term-level percentages should not be interpreted as treatment-attributable risks. The registry record does not clarify participant-level overlap between terms, timing, duration, or severity beyond the serious-event designation in this summary.

A count of participants affected is not the same as a count of all events, since a participant may experience more than one event. The record does not provide enough detail to determine event recurrence or the relationship of each event to treatment. Death counts are not reported in the serious-event fields. A separate secondary outcome describes treatment-emergent adverse events assessed using NCI CTCAE v4.0, but numerical results for that outcome are not reported in the registry record. These summaries support descriptive reading only, not a causal safety conclusion or a direct claim that one treatment is safer.

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

The trial’s stated aim was to evaluate safety and efficacy of ramucirumab or olaratumab in recurrent glioblastoma multiforme. Its primary endpoint was PFS-6, a milestone outcome based on being alive without progression through 6 months. The registry record supplies the endpoint definition, treatment descriptions, study design, and some serious-event counts, but no numerical result for the primary endpoint.

As a result, the posted record cannot establish how frequently PFS-6 was achieved in either group or how the groups differed on that outcome. It also cannot establish objective response, overall survival, pharmacokinetic or pharmacodynamic results, or anti-drug antibody results; these are listed as outcomes without numerical findings. The absence of reported results should not be interpreted as a null result, as evidence of no effect, or as proof that no analysis was performed.

The serious-event counts are descriptive. They do not establish that events were caused by treatment, and they do not provide a fair causal comparison between the two arms. Non-randomized allocation leaves open the possibility that the groups differed in ways related to outcomes. Open-label conduct and the lack of reported assessor masking are additional considerations for clinically assessed outcomes. No baseline characteristics or adjusted estimates are reported to help evaluate comparability.

More generally, an observed difference, if reported, would need to be considered alongside uncertainty, study design, outcome definitions, missing data, and the prespecified analysis plan. Those details are not fully available in the registry record. The study can therefore be described as a completed phase 2 investigation with a defined primary question, but its posted information does not support an estimate of comparative efficacy or a definitive treatment conclusion.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a registered research question and a reported statistical result. The endpoint is clearly framed as the percentage achieving PFS-6, and the registry provides a definition of progression. Yet the result itself is not reported. Without an estimate and an account of its precision, readers cannot determine what the study observed, regardless of how clearly the endpoint is described.

It also highlights why design labels are statistically consequential. A parallel-group study may look like a direct treatment comparison, but non-randomized allocation does not ensure that groups are comparable. Any numerical difference would need to be interpreted in light of potential confounding, especially when the registry record provides neither baseline characteristics nor an adjusted analysis. The open-label design also makes it important to know how outcome assessment was conducted.

The range of secondary outcomes underscores the need for transparent analysis planning. Safety, response, survival, drug exposure, biological effects, and anti-drug antibodies answer different questions. Their presence in a registry listing does not show that each result was reported or that multiplicity was addressed. Here, the analysis plan, missing-data procedures, and multiplicity approach are not reported in the registry record.

Finally, the serious-event counts demonstrate the limits of descriptive safety summaries. Counts can describe recorded experience, but without event detail, a causal framework, and suitable comparative analysis, they cannot establish that one treatment caused more harm than another. Statistical interpretation depends not only on the endpoint but also on allocation, follow-up, analysis populations, uncertainty, and complete reporting.

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 most direct limitation is that the registry record does not report the primary PFS-6 result or numerical results for the listed secondary outcomes. There are consequently no posted effect estimates or uncertainty measures with which to assess efficacy, precision, or the direction of any group difference.

The study was non-randomized and open-label. The record cautions that the treatment arms are not a like-for-like control comparison. It does not report baseline characteristics, the allocation procedure, masked outcome assessment, or covariate-adjusted results. These omissions limit assessment of group comparability and potential confounding.

The endpoint population is defined as enrolled participants who received at least one dose, but the record does not report analysis-specific denominators, participant flow, missing endpoint data, follow-up completeness, or methods for handling censoring and missingness. It also does not report the original sample-size justification, an interim-analysis plan, a detailed statistical plan, or a multiplicity strategy. The planning assumptions are illustrations and cannot fill those gaps.

For safety, the record provides affected counts and selected serious-event terms, but does not report event-level timing, recurrence, participant overlap, treatment attribution, or a comparative analysis. Death counts are not reported in the serious-event fields. These limitations apply to the registry record and do not establish what information may be available from other sources.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ramucirumab or Anti-PDGFR Alpha Monoclonal Antibody IMC-3G3 in Treating Patients With Recurrent Glioblastoma Multiforme — NCT00895180.
• Registry record last updated 2017-12-27; status last verified 2017-11.
• Results first posted 2017-03-29.
• 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

NCT00895180 is a completed, open-label, non-randomized phase 2 study of ramucirumab and olaratumab in recurrent glioblastoma multiforme. The registry lists enrollment of 80, a start date of 2010-07, primary completion on 2012-06-22, and Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins as sponsor. The parallel groups received intravenous treatment on day 1, with courses scheduled every 14 days unless progression or unacceptable toxicity occurred.

The primary outcome was PFS-6, defined using progression or death, in enrolled participants who received at least one dose. The registry record does not report its result or numerical findings for the listed secondary outcomes. Serious-event affected counts are recorded for both groups, along with selected serious-event terms. Because allocation was non-randomized and numerical efficacy results are absent, the record supports a description of the study design and outcome questions, but not a comparative treatment-effect estimate.