Phase 2 Study to Investigate the Efficacy and Safety of Aldoxorubicin in Subjects With Glioblastoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2 Study to Investigate the Efficacy and Safety of Aldoxorubicin in Subjects With Glioblastoma (NCT02014844), a randomized phase 2 study. The primary outcome is Objective Response Rate (Complete Response and Partial Response).

2. Clinical Question

3. Trial Design

This was an open-label pilot Phase 2 study of aldoxorubicin in subjects with glioblastoma whose tumors had progressed following prior treatment. The official title describes the intended population as subjects with unresectable glioblastoma previously treated with surgery, radiation and temozolomide. The registry record lists Glioblastoma as the condition and ImmunityBio, Inc. as the sponsor. The study status is completed.

The study began in 2014-03, and primary completion was recorded in 2016-12. Enrollment was 28. The listed interventions were intravenous aldoxorubicin at 250 mg/m2 and 350 mg/m2. The outcome record assigns 21 participants to the 250 mg/m2 group and 7 to the 350 mg/m2 group. The registry record does not explain the rationale for the group sizes or the process used to assign participants to doses.

There is an important design detail to keep in mind: allocation is listed as randomized, masking as none, and the model as single-group, while the outcome data are presented by dose group. The registry record does not explain how those design labels relate to one another, describe a randomization procedure, or specify whether the dose groups were intended as a formal head-to-head comparison. The study was open-label, so masking is not listed.

The primary outcome was objective response rate, measured up to 6 months. The record defines response using complete and partial response criteria from the RANO working group. It lists one primary outcome measure and no posted secondary outcomes. No statistical analysis is reported in the registry record.

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

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 Rate (Complete Response and Partial Response), measured over up to 6 months.

The primary endpoint is objective response rate (ORR), recorded as the count of participants with a complete response or partial response. The timeframe is up to 6 months. The registry definition uses RANO working group criteria, which combine imaging findings with requirements concerning disease status, corticosteroid use and clinical status.

A complete response requires disappearance of enhancing measurable or non-measurable disease sustained for at least 4 weeks, no new lesions, stable or improved non-enhancing T2/FLAIR lesions, appropriate corticosteroid status, and stable or improved clinical status. The record notes that participants with non-measurable disease only cannot have a complete response. A partial response requires at least 50% decrease compared with baseline sustained for at least 4 weeks, no progression of non-measurable disease, no new lesions, stable or improved non-enhancing lesions on the same or lower corticosteroid dose, and stable or improved clinical status. Participants with non-measurable disease only cannot have a partial response.

ORR is used to describe the frequency of a predefined tumor response within a stated assessment period. It is a binary outcome at the participant level: a participant meets the response definition or does not. The endpoint does not, by itself, describe how long a response lasts beyond the required confirmation period, or provide a time-to-event measure. The registry record posts the response counts but does not report an estimated response proportion, confidence interval, or analysis method.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry outcome is binary at the participant level: each participant either met the objective response definition or did not. The posted data give counts of participants with a response and group sizes. A response proportion is often used to summarize a binary endpoint, but no response proportion is reported in the registry record. No confidence interval or statistical test is posted either.

What does a confidence interval convey?

In general, a confidence interval describes statistical uncertainty around an estimate under a specified method and its assumptions. It is not a guarantee that the true value lies inside the interval, nor does it account automatically for every source of bias or incomplete measurement. For this study, no interval is reported for ORR. The small number of recorded responses means that an estimate based on these counts would be imprecise; the registry record does not provide an interval with which to quantify that uncertainty.

What can a comparison test establish?

In general, an inferential comparison asks whether the observed difference between groups is compatible with a specified null hypothesis, given a statistical model. A p-value is one part of that assessment, not a measure of the size or clinical importance of an effect. The registry record reports no p-value, test statistic, or comparative estimate for ORR. It also does not identify an analysis population or state how participants were included in an analysis. Therefore, no formal dose comparison can be reconstructed from the posted outcome counts alone.

Why does the design description matter?

The registry lists randomized allocation, no masking, and a single-group model, while reporting outcome counts for two dose groups. These labels do not fully explain the design. Randomization refers to how participants are assigned; a model or analysis description concerns how outcomes are structured or evaluated. The record does not give a randomization procedure, state whether the dose groups were intended for a direct comparison, or explain why the study is classified as single-group. Interpretation should therefore remain with the descriptive counts rather than assume a particular randomized comparison.

What does the endpoint definition contribute?

The RANO-based criteria define which imaging and clinical findings qualify as a complete or partial response. Requiring persistence for at least 4 weeks helps distinguish a confirmed response from a transient observation. The criteria also account for new lesions, non-enhancing disease, corticosteroid status and clinical status. Clear criteria make the outcome more reproducible in principle, but the record does not describe assessor procedures, independent review, or the timing of assessments within the timeframe of up to 6 months.

How should planning calculations be understood?

In general, sample-size planning uses assumptions about the effect to detect, variability, significance level, power and allocation. A planning calculation based on an observed effect is an illustration, not evidence that a trial was designed prospectively to detect that effect. It is also not observed power. The registry record does not report the trial's sample-size justification or a prospective statistical plan. It reports enrollment of 28, with 21 participants in the 250 mg/m2 group and 7 in the 350 mg/m2 group, but does not explain these group sizes.

Why are sparse outcomes challenging?

When an endpoint has few recorded events, estimates can change substantially with the outcome of a small number of participants. General statistical methods for binary outcomes may use approximations or exact procedures, depending on the data and analysis plan. The registry record does not name a method for ORR, so it is not possible to assess which method, if any, was used. Over-dispersion is a general concern when observed variability exceeds what a chosen model expects; it is more directly relevant to certain count models than to a simple binary response endpoint. No model diagnostics or dispersion assessment are reported for this outcome.

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("250 mg/m^2 Aldoxorubicin", "350 mg/m^2 Aldoxorubicin")
n      <- c(21, 7)
events <- c(0, 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  250 mg/m^2 Aldoxorubicin  21  0  0.0  0.0  16.1  -0.0  15.5  0.1  15.4
ARM  350 mg/m^2 Aldoxorubicin  7  1  14.3  0.4  57.9  2.6  51.3  3.2  52.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no posted secondary outcomes. It reports no statistical analyses. A multiplicity strategy, such as a hierarchy of hypotheses or adjustment for multiple testing, is not reported in the registry record. The record also does not explain whether other outcomes or dose comparisons were examined outside the posted results. Without that information, the implications of multiple testing cannot be assessed.

Missing-data methods are not reported. The record does not say whether all enrolled participants had an outcome assessment, how participants without an assessment were handled, or whether a participant could be considered unevaluable. It also does not describe an analysis population, such as an intention-to-treat or per-protocol population. The response counts are posted by dose group, but their relationship to the enrolled population and any missing outcome assessments is not explained.

These omissions affect interpretation because the reported response counts cannot establish how missing assessments were treated or whether the analysis included every enrolled participant. Details on assessment schedules, response adjudication and the handling of incomplete follow-up would help evaluate the endpoint results. The registry record does not report these details, a statistical analysis plan, or interim analyses.

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: seizure (14.3%), hemiparesis (14.3%), encephalopathy (14.3%), somnolence (14.3%), febrile neutropenia (4.8%).

The registry reports serious adverse events by dose group. In the 250 mg/m2 group, 6 participants were affected among 21 at risk; in the 350 mg/m2 group, 2 were affected among 7 at risk. These figures describe participants with serious adverse events, not the total number of separate events. The record also reports 16 deaths in the 250 mg/m2 group and 7 in the 350 mg/m2 group. It does not provide enough context in these figures to attribute deaths to treatment or to a particular cause.

The listed serious adverse event terms include Seizure, Hemiparesis, Encephalopathy and Somnolence, each reported as 14.3%. Febrile Neutropenia and Mucosal Inflammation are each reported as 4.8%. These are registry-listed terms and percentages; the record does not explain whether a participant could contribute to more than one term or how the percentages were derived. The figures should not be read as comparative safety estimates or as evidence of causation. No statistical comparison of serious adverse events between dose groups is reported.

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

The result describes the primary outcome counts recorded by the registry: 0 participants with objective response in the 250 mg/m2 group and 1 participant in the 350 mg/m2 group. The endpoint used defined RANO working group criteria and had a timeframe of up to 6 months. These details show what outcome was counted and when it was assessed at a broad level.

The result does not provide a precise estimate of the response frequency in either group. The registry record posts no confidence interval or statistical analysis for ORR. The counts alone do not establish that the doses differ, and the record does not describe enough about allocation or analysis to support a formal dose comparison. A response count is also not a measure of response duration beyond the confirmation requirement in the endpoint criteria.

These results should not be interpreted as proof that aldoxorubicin did or did not work. The registry record describes a pilot Phase 2 study and posts a sparse set of response counts. It does not report a comparator receiving another treatment or no treatment, so the outcome counts cannot isolate a treatment effect from other explanations. Nor do the posted results establish a dose-response relationship.

The record also leaves key analytic details unreported, including missing-data handling, the analysis population, the statistical method, and a sample-size justification. Those details matter when assessing how robustly the outcome was measured and how much uncertainty surrounds the observed counts. The appropriate interpretation is consequently narrow: the registry recorded the stated response counts in the two aldoxorubicin dose groups, while comparative and causal conclusions are not established by the posted results.

14. Why This Trial Matters Statistically

This trial illustrates why a clinical outcome count should be interpreted alongside its endpoint definition, study design and analysis details. ORR is not simply an imaging impression: the registry definition requires specified findings over time and incorporates non-enhancing disease, corticosteroid status and clinical status. Those criteria determine which participants are counted as responders.

The study also shows the limits of a sparse binary outcome. The posted response counts are 0 participants in the 250 mg/m2 group and 1 participant in the 350 mg/m2 group. Without an uncertainty interval or an inferential analysis, these counts do not quantify how precisely the response frequency is estimated or whether the dose groups differ. This is especially relevant when the group sizes are 21 and 7 participants.

Design labels need to be read carefully. The registry lists randomized allocation and a single-group model, while reporting two dose groups. Without the assignment procedure and a defined comparative analysis, it is not possible to determine the intended role of randomization in interpreting the dose-group results. Transparent reporting of the statistical plan, analysis population and missing-data approach would make the results easier to evaluate.

For biostatistical interpretation, the central lesson is to distinguish what is directly reported from what would require additional analysis. The record supports a descriptive account of the posted response and safety counts. It does not report a comparative treatment estimate, its precision, or a prespecified basis for judging the findings.

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 registry record gives limited information for evaluating the primary outcome. It reports response counts and group sizes, but no response estimate, confidence interval, p-value, or statistical analysis. The sample-size justification and prospective analysis plan are not reported in the registry record. As a result, the adequacy of the enrollment for estimating ORR or comparing doses cannot be assessed from the record.

Several design features also remain unclear. Allocation is listed as randomized, while the model is listed as single-group and the results are reported for two dose groups. The randomization procedure and intended comparison are not reported. The study is open-label, and the record does not describe independent outcome review or assessor procedures.

The endpoint timeframe is up to 6 months, but assessment frequency and handling of incomplete assessments are not reported. Missing-data methods, analysis populations, and the number of participants with evaluable outcome data are not specified beyond the posted group counts. The record also does not report secondary outcomes or a multiplicity strategy.

Finally, safety counts are reported without a comparative statistical analysis or sufficient detail to determine causal attribution. These limitations do not alter the posted counts, but they restrict how much can be concluded about precision, between-group differences, and the broader interpretation of the results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 2 Study to Investigate the Efficacy and Safety of Aldoxorubicin in Subjects With Glioblastoma — NCT02014844.
• Registry record last updated 2024-05-29; status last verified 2015-09.
• Results first posted 2024-05-29.
• 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

NCT02014844 is a completed, open-label pilot Phase 2 study of aldoxorubicin in subjects with glioblastoma whose tumors had progressed following prior treatment. The study began in 2014-03, and primary completion was recorded in 2016-12. Enrollment was 28.

The registry reports intravenous aldoxorubicin dose groups of 250 mg/m2 and 350 mg/m2, with 21 and 7 participants, respectively. The primary outcome was objective response rate by RANO working group criteria, with a timeframe of up to 6 months. The posted counts were 0 participants with a response in the 250 mg/m2 group and 1 in the 350 mg/m2 group.

No statistical analyses are posted. Comparative estimates, confidence intervals, missing-data methods, analysis populations, and sample-size justification are not reported in the registry record. Allocation is listed as randomized, while the model is listed as single-group; the relationship between those design descriptions is not explained.