Efficacy, Safety and CNS Exposure of G-202 (Mipsagargin) in Patients With Recurrent or Progressive Glioblastoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy, Safety and CNS Exposure of G-202 (Mipsagargin) in Patients With Recurrent or Progressive Glioblastoma (NCT02067156), a na phase 2 study. The primary outcome is 6-month Progression-free Survival (PFS).

2. Clinical Question

The registry record identifies this as an open-label, single-arm Phase II study in patients whose glioblastoma had recurred or progressed. Its stated purpose was to evaluate efficacy, safety, and central nervous system exposure of G-202. The primary endpoint focuses on progression-free status at a fixed time point, rather than a comparison between assigned treatments.

Progression is defined using criteria from the Response Assessment in Neuro-Oncology Working Group for high-grade glioma. The listed criteria include specified increases in enhancing lesions, significant increases in T2/FLAIR nonenhancing lesions, new lesions, clear progression of nonmeasurable lesions, or definite clinical deterioration not attributable to other causes or a reduction in corticosteroid dose. The endpoint also counts death within the stated period as an event.

The registry record lists an enrollment of 26, but does not report how many participants were response-evaluable or the number meeting the primary endpoint. It therefore does not provide the observed 6-month progression-free survival percentage or a treatment comparison. The question that can be addressed from the record is what endpoint the study intended to assess and what design features shape its interpretation—not whether G-202 performed better than another treatment.

3. Trial Design

This was a Phase II, open-label, single-group study of G-202 (mipsagargin) in patients with recurrent or progressive glioblastoma. The registry record lists enrollment of 26 and describes the intervention as intravenous infusion on 3 consecutive days of a 28-day cycle. The study is marked completed. Its recorded start was 2014-02, and its primary completion was 2016-12.

There was no randomized allocation, masking, or separate comparator group. Consequently, the design does not provide a concurrent control against which to compare progression-free survival, overall survival, tumor response, or adverse events. In a single-group study, the observed outcomes describe participants who received the intervention; they do not by themselves estimate how those same participants would have fared under a different treatment or without treatment.

The primary outcome was 6-month progression-free survival, expressed as a percentage of patients meeting the endpoint definition. The registry specifies a response-evaluable population and states that patients must have received at least 2 cycles and must not have progressed or died within 6 months of beginning treatment. The number in this analysis population and the endpoint result are not reported in the registry record.

Listed secondary outcomes are toxicity assessed by CTCAE v 4.03 criteria, objective tumor response rate, duration of progression-free survival, overall survival, and tumor biomarkers. The registry records six outcome measures in total, but does not report analyses for them. Details such as eligibility criteria beyond the condition and disease status, the planned statistical analysis, sample-size justification, interim analyses, and follow-up procedures are not reported in the registry record. The design details that are reported support a description of the study structure, but not a reconstruction of unreported methods or results.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: response-evaluable participants

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 6-month Progression-free Survival (PFS), measured over 6 months.

The primary endpoint is 6-month progression-free survival, described as a percentage of patients who received at least 2 cycles of G-202 and had not progressed or died within 6 months of beginning treatment. The endpoint population is identified as response-evaluable participants. The registry record does not state how many participants entered that population or how many met the endpoint.

This fixed-time endpoint asks whether participants were alive and had not experienced disease progression by a specified follow-up point. Progression is defined by criteria for high-grade glioma from the Response Assessment in Neuro-Oncology Working Group. These criteria include changes in enhancing and nonenhancing lesions, new lesions, progression of nonmeasurable lesions, and definite clinical deterioration under the conditions described in the registry. Death within 6 months also means a participant does not meet the progression-free endpoint.

As a general statistical concept, a fixed-time proportion can communicate the share of an analysis population meeting an outcome definition at a particular time. It differs from describing the time until progression or death for each participant. The registry lists the primary measure as a count of participants, but does not report a percentage, confidence interval, or analysis method for the endpoint.

The requirement to have received at least 2 cycles is part of the endpoint description. The record does not explain how participants who received fewer cycles, had incomplete follow-up, or lacked an evaluable assessment were handled. Those details matter when interpreting which participants contribute to a fixed-time estimate, and are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

This study assigned participants to one group receiving G-202, with no random allocation and no comparator arm. In general, a single-group study can describe outcomes observed during follow-up in that group. It cannot directly estimate a between-group treatment contrast because there is no separate group receiving a different intervention or control condition. The record does not report a planned comparison with external or historical data, so none should be assumed.

Random allocation is a method used in comparative trials to make treatment groups similar, on average, with respect to measured and unmeasured characteristics. It is not part of this study’s design. Without randomization and a concurrent comparator, differences between observed outcomes and expectations based on other settings could reflect differences in participants, care, outcome assessment, or follow-up, as well as any effect associated with the intervention. The record does not provide information to quantify those influences.

How should the primary endpoint be understood?

The primary endpoint is a binary status at 6 months: whether a response-evaluable participant received at least 2 cycles and remained alive without progression during the specified period. The registry lists the measure as a count of participants and describes the result as a percentage. In general, a binary endpoint classifies each participant into one of two outcome categories according to a prespecified definition. A proportion is then based on the number meeting the definition relative to the analysis population.

The analysis population matters because the endpoint is defined for response-evaluable participants, not simply for everyone enrolled. The registry record does not report the number response-evaluable, the number meeting the definition, or the treatment of participants with missing or incomplete assessments. It therefore does not allow the endpoint proportion or its precision to be reconstructed.

The endpoint is a fixed-time measure. This is distinct from a time-to-event analysis that uses the timing of progression or death and may account for participants whose follow-up ends before an event is observed. Although the study also lists duration of progression-free survival as a secondary outcome, the registry record does not describe the analysis method for that outcome. The primary endpoint’s stated 6-month threshold does not, by itself, establish that a time-to-event model was used.

What would uncertainty measures contribute?

General statistical explanation: a confidence interval describes a range of values compatible with the observed data under a specified method and its assumptions. It communicates sampling uncertainty around an estimate; it is not a guarantee that the true value lies in the interval, and it does not address every source of bias. For a proportion, precision depends in part on the number of participants contributing to the estimate and the distribution of outcomes. No confidence interval or primary endpoint estimate is reported in the registry record.

A hypothesis test, if planned and reported, would address a defined statistical question under a specified model. The record does not report a primary test, a null value, a significance level, or a p-value. No test result should be inferred from the study phase or from its enrollment.

Why can over-dispersion matter?

General statistical explanation: some count models assume that variability follows a particular relationship to the average count. Over-dispersion occurs when observed variability is greater than that model assumes. If it is ignored, standard errors can be too small and confidence intervals or tests can be misleading. This concern is relevant to some count outcomes, but the primary endpoint in this study is described as a participant count for a binary status. The registry record does not report a model for that endpoint or an over-dispersion assessment, so it is not possible to say whether either was used or needed.

What do planning illustrations mean?

General statistical explanation: sample-size planning asks how many participants might be needed under specified assumptions to detect a chosen effect with a stated probability, often called power. A planning calculation is not an observed trial result and does not show that the study had a particular probability of detecting an effect after the fact. The record’s planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effect sizes expressed as fractions of an observed effect. It also distinguishes total event counts for time-to-event outcomes from participants per arm for other outcomes.

Those assumptions describe planning illustrations, not the design of this single-group trial: there were no two randomized arms to allocate equally. The registry record does not report its own sample-size justification. No illustration values are stated in the record information available for this analysis, and no numerical planning result should be inferred. Planning values, when available, would remain hypothetical and should not be described as observed power.

The registry records zero analyses. It does not report the statistical analysis plan, model specifications, adjustment for covariates, handling of repeated measures, or any interim analysis. General statistical concepts can explain why those choices matter, but cannot establish which choices were made for this study.

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("G-202 (Mipsagargin)")
n      <- c(21)
events <- c(1)
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  G-202 (Mipsagargin)  21  1  4.8  0.1  23.8  0.8  22.7  1.1  22.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies 6 outcome measures in total. The primary outcome is 6-month progression-free survival. Listed secondary outcomes include toxicity assessed by CTCAE v 4.03 criteria, objective tumor response rate, duration of progression-free survival, overall survival, and biomarkers in tumor. Considering multiple outcomes can raise a multiplicity issue: when many hypotheses are tested, the chance of at least one apparently unusual result may increase. General statistical approaches can address this, for example by defining a primary outcome in advance or adjusting inference across tests. The registry record does not report a multiplicity strategy, the number of formal tests, or analyses of the secondary outcomes.

Missing data are particularly relevant to a fixed-time endpoint because a participant may not have an evaluable disease assessment at the specified time. The endpoint is restricted to response-evaluable participants and includes a requirement to have received at least 2 cycles. The record does not report how response evaluability was determined, how many participants were excluded, how incomplete follow-up was handled, or whether missing outcomes were imputed or otherwise addressed.

The record reports zero analyses, so it does not provide details of analysis populations beyond the primary endpoint’s response-evaluable description. It does not state whether all enrolled participants, all treated participants, or another population was used for each secondary outcome. There is also no reported statistical analysis plan, prespecified handling of missing values, or sensitivity analysis. These omissions limit assessment of whether the reported endpoint definitions and analysis populations were applied consistently. They do not establish that any particular method was or was not used outside the registry record.

12. Safety Results

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

Deaths

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: diarrhea (3.8%), nausea (3.8%), symptomatic vomiting (3.8%), vomiting (3.8%), infusion reaction (3.8%).

The registry lists 26 participants at risk in the G-202 group for both serious and other adverse events. It records 6 participants with serious adverse events and 24 with other adverse events. The record also lists 22 deaths. These are counts, not comparative rates against a control group, and the study has no comparator arm.

The listed serious adverse event terms are Diarrhea, Nausea, Symptomatic Vomiting, Vomiting, Infusion reaction, and Creatinine increased; each is shown as 3.8%. The registry record does not state whether a participant could contribute to more than one term, so these percentages should not be added or treated as mutually exclusive categories. It also does not report the timing, duration, outcome, or causal attribution for these events in the information recorded.

Seriousness is a classification of an adverse event and is not interchangeable with severity or proof that the intervention caused the event. Likewise, the death count alone does not indicate when the deaths occurred or whether they were attributed to G-202; those details are not reported in the registry record. The safety figures describe events recorded in this study group and cannot establish comparative risk.

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

The registry record establishes that a completed, open-label, single-arm Phase II study evaluated G-202 in patients with recurrent or progressive glioblastoma. It specifies a 6-month progression-free survival endpoint and records safety counts. It does not report the primary endpoint result, an efficacy estimate, or statistical analyses. The study’s primary finding therefore cannot be summarized numerically from the record.

The enrollment of 26 should not be mistaken for the primary endpoint denominator. The endpoint is defined for response-evaluable participants who received at least 2 cycles, and the number meeting those conditions is not reported. Without that denominator and the number of participants who remained progression-free and alive, the endpoint percentage cannot be established.

The single-group design also limits what any observed outcomes could mean. If outcomes were reported, they would describe the participants treated in this study. In the absence of a concurrent comparator, they would not by themselves show how outcomes would differ under another treatment or establish that G-202 caused a particular result. Open-label conduct and unreported details of assessment and missing-data handling further matter when judging precision and potential bias.

The safety record lists serious adverse events in 6 participants, other adverse events in 24 participants, and 22 deaths. These counts do not determine whether events were related to treatment, and the absence of a control group prevents comparative safety interpretation. The term-specific percentages likewise do not supply causal or comparative evidence.

General interpretation: statistical evidence is most informative when an estimate is accompanied by its analysis population, uncertainty interval, endpoint definition, and analysis method. Those primary efficacy details are not reported in the registry record. The study description and safety counts can be reported as such, but should not be extended into a claim that treatment did or did not work.

14. Why This Trial Matters Statistically

This study illustrates why design and reporting determine the questions that statistical results can answer. A single-group study can document outcomes among participants who received an intervention, but it cannot make a randomized comparison with an alternative. That distinction remains important even when a study is Phase II and has a clearly specified clinical endpoint.

The primary endpoint is a fixed-time progression-free status measure with a detailed progression definition. That specificity helps clarify what counts as an event, including radiographic changes, clinical deterioration under stated conditions, and death. At the same time, the requirement for response-evaluable participants who received at least 2 cycles makes the analysis population central to interpretation. The registry record does not report the denominator or the endpoint result.

The registry also shows why outcome counts and causal conclusions are different. Safety events are recorded in the treatment group, but there is no control group for comparison, and event attribution is not reported. Counts can describe what was recorded without establishing how much was caused by treatment or whether the frequency differs from another setting.

Finally, the record lists several secondary outcomes but no analyses. General statistical practice distinguishes a primary question from multiple additional outcomes, and transparent reporting of analysis populations, missing-data handling, uncertainty, and multiplicity helps readers judge the strength of evidence. Here, those methods and the primary efficacy estimate are not reported in the registry record. The study is therefore statistically informative about its design and stated endpoint, while its efficacy findings cannot be evaluated from the recorded results.

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 main trial-specific limitation is the absence of a comparator. With one treatment group and no random allocation, the study cannot directly estimate a contrast between G-202 and another intervention or control condition. Its open-label design also means masking was absent. The registry record does not report details that would clarify how outcome assessment was protected from potential influence.

The primary endpoint result is not reported in the registry record. Neither the number of response-evaluable participants nor the number meeting the endpoint definition is stated. The endpoint requires at least 2 cycles and no progression or death within 6 months, but the record does not explain the handling of participants who received fewer cycles, lacked an evaluable assessment, or had incomplete follow-up. This prevents assessment of the analysis denominator and missing-data implications.

The record lists 26 enrolled participants and several safety counts, but does not report the primary efficacy estimate, a confidence interval, a statistical test, or analyses of secondary outcomes. It also does not report a statistical analysis plan, sample-size justification, interim analyses, or methods for multiplicity. These gaps make it impossible to evaluate the precision of the primary endpoint or the planned basis for statistical inference.

The safety counts lack reported timing and causal attribution in the registry record. Since the study has no comparator, the counts cannot quantify a difference in safety relative to another group. The posted record is therefore limited for evaluating efficacy and comparative safety, even though it describes the intervention schedule, endpoint definition, and some adverse event counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy, Safety and CNS Exposure of G-202 (Mipsagargin) in Patients With Recurrent or Progressive Glioblastoma — NCT02067156.
• Registry record last updated 2024-05-21; status last verified 2024-05.
• Results first posted 2024-05-21.
• 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

The registry record describes a completed, open-label, single-arm Phase II study of G-202 (mipsagargin) in patients with recurrent or progressive glioblastoma. Enrollment was 26. G-202 was administered by intravenous infusion on 3 consecutive days of a 28-day cycle. The primary endpoint was 6-month progression-free survival among response-evaluable participants, with the definition requiring at least 2 cycles and no progression or death within 6 months.

The registry lists toxicity, objective tumor response, duration of progression-free survival, overall survival, and tumor biomarkers as secondary outcomes. It records 6 participants with serious adverse events, 24 with other adverse events, and 22 deaths. The primary efficacy result, analysis populations beyond the response-evaluable description, statistical methods, missing-data handling, and sample-size justification are not reported in the registry record.