This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Stage 1: Marizomib + Bevacizumab in WHO Gr IV GBM; Stage 2: Marizomib Alone; Stage 3: Combination of Marizomib and Bevacizumab (NCT02330562), a na phase 1, phase 2 study. The primary outcome is Overall Survival (OS) - Part 3 Cohorts.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02330562 |
| Phase | Phase 1, Phase 2 |
| Condition | Malignant Glioma, Glioblastoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 121 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Celgene |
| Results posted | Yes |
2. Clinical Question
The study evaluated marizomib (MRZ) in several study parts, including use with bevacizumab (BEV) and use as a single agent. Its overall population was people with WHO Grade IV malignant glioma, including glioblastoma, in first or second relapse. The brief summary describes participants as not previously treated with bevacizumab or another anti-angiogenic agent or proteasome inhibitor for malignant glioma.
The primary question identified in the registry record concerns overall survival in Part 3: how long treated participants lived from their first dose of study drug, with death from any cause as the event. The endpoint covers all treated participants in Part 3, rather than a randomized comparison between treatment groups. The registry describes Part 3 as a Phase 2 combination cohort using MRZ with intra-patient dose escalation and BEV at a fixed dose.
The broader study also investigated MRZ alone, combination treatment in other cohorts, enteral administration, and repeat-dose pharmacokinetics. These are distinct study questions and should not be collapsed into the Part 3 survival endpoint. The record lists adverse events, serious adverse events, dose-limiting toxicity, dose-limiting adverse events, radiographic objective response rate, progression-free survival, and overall survival among the outcomes.
Population
People with WHO Grade IV malignant glioma, including glioblastoma, in first or second relapse, as described in the brief summary. The primary endpoint population was all treated participants in Part 3.
Intervention
Marizomib, studied as a single agent and in combination with bevacizumab across different parts. Part 3 used combination treatment with intra-patient MRZ dose escalation and fixed-dose BEV.
Comparator
No randomized comparator is identified. The registry lists the study as single-group, with allocation not applicable and no masking.
Primary question
What was overall survival from first study-drug dose among treated participants in Part 3? The numerical estimate is not reported in the registry record.
3. Trial Design
This was a multicenter, open-label Phase 1/2 study. The registry lists the allocation as not applicable, the model as single group, and masking as none. It records enrollment of 121 and status as completed. The study started on 2015-04-15, with primary completion on 2021-06-02.
The official title describes dose escalation of MRZ with BEV in bevacizumab-naïve participants with WHO Grade IV malignant glioma, followed by Phase 2 studies of single-agent MRZ and MRZ with BEV, as well as a Phase 1 dose-escalation study using enteral MRZ with BEV. The brief summary divides the study into five parts. Part 1 was a Phase 1 combination study; Part 2 was a Phase 2 single-agent MRZ study; Part 3 was a Phase 2 combination study; Part 4 evaluated enteral MRZ with fixed-dose BEV; and Part 5 evaluated repeat-dose pharmacokinetics of IV MRZ with ECG.
The record gives dosing details for Part 1 and Part 2. In Part 1, MRZ was given as a 10 minute IV infusion on Days 1, 8, and 15, while BEV was given by IV infusion on Days 1 and 15 of each 28-day cycle. In Part 2, MRZ was given as a 10 minute IV infusion on Days 1, 8, and 15 of each 28-day cycle. The brief summary describes Part 3 as combination treatment with intra-patient MRZ dose escalation and fixed-dose BEV. The registry record does not provide a complete Part 3 dosing description in the available arm description.
These parts address different treatment settings and cannot be treated as equivalent arms in a head-to-head trial. The record does not identify random assignment, masking, or a concurrent control group. The protocol’s rationale for enrollment, sample-size justification, and planned interim analyses are not 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.
Only the first 6 of 11 groups are shown.
Overall Study
| Stage | Part 1 Cohort 1 | Part 1 Cohort 2 | Part 1 MTD + Dose Expansion Cohort | Part 2 Cohort | Part 3 Cohort 1 | Part 3 Cohort 2 |
|---|---|---|---|---|---|---|
| STARTED | 6 | 3 | 27 | 30 | 31 | 10 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 3 | 27 | 30 | 31 | 10 |
Reasons for not completing this period:
| Reason | Part 1 Cohort 1 | Part 1 Cohort 2 | Part 1 MTD + Dose Expansion Cohort | Part 2 Cohort | Part 3 Cohort 1 | Part 3 Cohort 2 |
|---|---|---|---|---|---|---|
| Adverse Event | 0 | 0 | 3 | 0 | 3 | 1 |
| Participant decision | 1 | 0 | 4 | 1 | 5 | 2 |
| Disease progression | 5 | 3 | 20 | 28 | 23 | 7 |
| Other reasons | 0 | 0 | 0 | 1 | 0 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: All treated participants in Part 2 Cohort
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.
Only the first 6 of 12 groups are shown.
| Characteristic | Unit | Part 1 Cohort 1 | Part 1 Cohort 2 | Part 1 MTD + Dose Expansion Cohort | Part 2 Cohort | Part 3 Cohort 1 | Part 3 Cohort 2 |
|---|---|---|---|---|---|---|---|
| Participants analysed | 6 | 3 | 27 | 30 | 31 | 10 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 | 3 | 20 | 23 | 25 | 7 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 7 | 7 | 6 | 3 |
| Sex: Female, Male: Female | Participants | 1 | 0 | 12 | 13 | 14 | 7 |
| Sex: Female, Male: Male | Participants | 5 | 3 | 15 | 17 | 17 | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 5 | 2 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 | 3 | 22 | 28 | 31 | 9 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 2 | 0 | 3 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 2 | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 5 | 3 | 21 | 27 | 27 | 9 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 1 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 1 | 3 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Survival (OS) - Part 3 Cohorts, measured over From first dose to death, assessed up approx. 42 weeks.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint was overall survival (OS) in all treated participants in Part 3. OS was defined as the time from the date of the first dose of study drug to the date of death from any cause. Participants who were alive were to be censored at their last follow-up visit. The listed assessment period was from first dose to death, assessed up to approximately 42 weeks.
OS is a time-to-event endpoint: it accounts for both whether an event occurred and how long participants were followed before the event or censoring. In general, this type of endpoint is useful when the timing of an event matters and follow-up durations differ. Censoring allows the analysis to retain information from participants who have not had the event by their last recorded follow-up, without treating their follow-up as if it continued indefinitely.
The registry identifies the endpoint summary as a median with a 95% confidence interval, but the numerical median and interval are not reported in the registry record. As a result, the posted record does not establish the observed Part 3 median OS or the precision of that estimate. The endpoint definition and intended population are clear; the result itself is not available in the information recorded for this outcome.
OS refers to death from any cause, not only death attributed to malignant glioma or to study treatment. This makes the outcome definition distinct from progression-free survival, radiographic response, and adverse-event outcomes, which the registry lists separately.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies OS as the primary endpoint for Part 3, with all treated participants in that part forming the endpoint population. It defines the time origin as the first dose of study drug, the event as death from any cause, and the censoring time for participants still alive as their last follow-up visit. However, it does not report the numerical median OS or its 95% confidence interval. Without those values, the posted record does not permit a direct description of the observed survival time or its statistical precision.
The study is listed as single-group, with allocation not applicable and no masking. Its several parts include different treatment regimens and administration approaches. Consequently, the registry record does not describe a randomized, like-for-like comparison from which to estimate a treatment contrast. The Part 3 endpoint is a summary of outcomes among treated participants in that cohort; it is not, by itself, an estimate of how outcomes would differ under an alternative treatment.
The record lists 121 participants enrolled overall. That total is not a Part 3 endpoint denominator. The Part 3 endpoint population is specified as all treated participants in Part 3, but the number treated in that endpoint population is not reported in the registry record. The safety listing gives at-risk counts for individual cohorts, but those cohort figures should not be substituted for an endpoint analysis population unless the registry explicitly identifies them as such.
The registry lists nine outcome measures and names additional outcomes including adverse events, serious adverse events, dose-limiting toxicity, dose-limiting adverse events, radiographic objective response rate, progression-free survival, and OS. Numerical results for those outcomes are not reported in the record details used for this analysis. The listed serious adverse event counts and affected-participant counts provide safety descriptions by cohort, but they do not supply the missing OS estimate or establish a comparative treatment effect.
The record contains no analysis entries. It therefore does not give a reported inferential analysis, such as a hazard ratio, p-value, or treatment-group contrast, for the primary endpoint. The direction and magnitude of an effect cannot be inferred from the endpoint definition, study status, enrollment total, or safety counts. These design and reporting features limit interpretation to the study structure and the outcomes explicitly recorded.
In general, a confidence interval describes uncertainty around an estimated quantity; its width reflects how precisely that quantity has been estimated under the analysis assumptions. Here, the registry names a 95% confidence interval but provides no interval limits. Precision therefore cannot be assessed from the endpoint information in the registry record.
9. Statistical Methods Explained
The registry describes the primary outcome as a median time-to-event measure with a 95% confidence interval. The endpoint is OS in all treated participants in Part 3. The registry defines OS from first study-drug dose to death from any cause, with participants alive at last follow-up censored at that visit. The numerical estimate and confidence limits are not reported in the registry record, so the statistical method can be explained, but its numerical result cannot be interpreted from this record.
What does a median survival time represent?
In general, the median for a time-to-event outcome is the time at which the estimated event-free proportion reaches the midpoint of the population under study. For OS, the event is death. A median is a distribution summary; it is not the average follow-up time, nor does it state that every participant experienced the event at that time. Participants with shorter or longer observed follow-up, including participants censored while alive, contribute information according to their observed time and event status.
The registry gives the median as the intended summary but does not state the numerical median. It also does not report the number of deaths in the Part 3 endpoint analysis or the follow-up distribution for that population. The deaths listed in the safety record are grouped by cohort and are not identified as a complete endpoint analysis listing. They should not be used to reconstruct the OS median.
Why is censoring relevant?
In general, censoring occurs when a participant’s event time is not observed during the available follow-up. The record specifies that participants alive at last follow-up are censored at that visit. Censoring preserves the observed follow-up information without asserting that the participant remained alive after the last known contact. It also means that a time-to-event estimate depends on the timing of follow-up and on the assumptions used to handle censoring.
The record does not describe additional censoring rules, follow-up completeness, or methods for handling missing endpoint information. Those details are not reported in the registry record. The stated endpoint definition is therefore not enough to assess whether censoring patterns differed across participants or how any missing observations were handled.
What does a confidence interval communicate?
In general, a confidence interval expresses uncertainty around an estimated value under a statistical procedure and its assumptions. It helps readers distinguish a relatively precise estimate from one with substantial uncertainty. A confidence interval is not a guarantee that the true value lies within the particular interval, and it does not by itself establish a treatment effect. The registry specifies a 95% confidence interval for the median OS but does not report either limit. Thus, the precision of the estimate cannot be evaluated from the registry record.
How should the design shape interpretation?
The registry lists the trial as single-group, with no masking and allocation not applicable. In general, an outcome observed in one treated group describes that group’s course, but a causal comparison requires an appropriate counterfactual comparison. A single-group cohort cannot, on its own, separate the effects of treatment from other influences on outcome. This is particularly important when reading survival summaries: an observed median does not automatically quantify a benefit or harm relative to another treatment.
The study contains distinct parts, including single-agent MRZ and MRZ with BEV, but these are not described as randomized arms. The primary endpoint population is specifically all treated participants in Part 3. Results from other parts should not be pooled or compared as if treatment assignment and participant characteristics were balanced by randomization; the record does not report such a design or analysis.
What do planning calculations mean?
In general, sample-size calculations estimate the number of participants or events that might be required under stated assumptions to detect a specified effect with a chosen statistical procedure. Such calculations are planning illustrations, not observed power and not evidence that a trial detected an effect. The registry’s stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event outcomes, the description refers to a total number of events; for other outcomes, it refers to participants per arm.
Those assumptions describe an illustrative calculation rather than the design of this single-group trial. The trial’s own sample-size justification is not reported in the registry record. No planning result should be read as a trial outcome, as the number actually analyzed, or as observed power. A sample-size illustration based on an observed effect also depends on that effect estimate, which is not reported for the primary endpoint in the record.
What analysis details are unavailable?
The registry record lists no analysis entries. It does not report a hazard ratio, p-value, confidence-interval limits, or a model specification for the primary endpoint. It also does not report whether any adjusted analyses were planned or conducted. The registry names nine outcome measures, but the number of listed outcomes does not reveal the analysis hierarchy or which results were formally tested. Those details are not reported in the registry record.
In general, time-to-event analyses can account for different follow-up durations and censoring, but the particular estimator and assumptions matter. The record’s designation of a median and confidence interval does not identify every step of the analysis. Without the numerical estimate and method details, readers can identify the intended endpoint and population but cannot reproduce or independently assess its statistical result.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists nine outcome measures, including adverse events, serious adverse events, dose-limiting toxicity, dose-limiting adverse events, radiographic objective response rate, progression-free survival, and OS. It identifies OS in Part 3 as the primary outcome. The registry record does not report a multiplicity strategy, such as a testing hierarchy or adjustment across outcomes. It also does not report interim analyses or a statistical analysis plan. The number of outcomes alone does not show which comparisons were intended to support formal claims.
Missing-data handling is only partly described for the primary endpoint. Participants alive at their last follow-up visit were to be censored at that visit. The registry record does not report how missing visits, incomplete follow-up, or other missing endpoint information were handled, nor does it describe sensitivity analyses for those circumstances.
The primary endpoint population is all treated participants in Part 3. The record does not report the number in that analysis population or how it relates to participants enrolled overall. It also does not state whether any participants were excluded from the endpoint analysis or give reasons for exclusions. Those population details are not reported in the registry record.
Because no analysis entries are listed and the numerical OS result is absent, the registry record does not allow assessment of the actual endpoint analysis, precision, or potential influence of missing data. The listed safety counts remain descriptive cohort information and do not resolve those gaps.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Part 1 Cohort 1 | 1 | 6 | 16.7% |
| Part 1 Cohort 2 | 0 | 3 | 0.0% |
| Part 1 MTD + Dose Expansion Cohort | 12 | 27 | 44.4% |
| Part 2 Cohort | 10 | 30 | 33.3% |
| Part 3 Cohort 1 | 14 | 31 | 45.2% |
| Part 3 Cohort 2 | 5 | 10 | 50.0% |
| Part 4 Cohort 1 | 1 | 1 | 100.0% |
| Part 4 Cohort 2 | 0 | 1 | 0.0% |
| Part 4 Cohort 3 | 0 | 1 | 0.0% |
| Part 4 Cohort 4 | 1 | 5 | 20.0% |
| Part 4 Cohort 5 | 3 | 6 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Part 1 Cohort 1 | 5 of 6 |
| Part 1 Cohort 2 | 2 of 3 |
| Part 1 MTD + Dose Expansion Cohort | 21 of 27 |
| Part 2 Cohort | 24 of 30 |
| Part 3 Cohort 1 | 25 of 31 |
| Part 3 Cohort 2 | 9 of 10 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Part 1 Cohort 1 | 6 of 6 |
| Part 1 Cohort 2 | 3 of 3 |
| Part 1 MTD + Dose Expansion Cohort | 26 of 27 |
| Part 2 Cohort | 30 of 30 |
| Part 3 Cohort 1 | 31 of 31 |
| Part 3 Cohort 2 | 10 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Part 1 Cohort 1 | Part 1 Cohort 2 | Part 1 MTD + Dose Expansion Cohort | Part 2 Cohort | Part 3 Cohort 1 | Part 3 Cohort 2 |
|---|---|---|---|---|---|---|---|
| Confusional state | Psychiatric disorders | 1 of 6 | 0 of 3 | 3 of 27 | 1 of 30 | 3 of 31 | 1 of 10 |
| Convulsion | Nervous system disorders | 1 of 6 | 0 of 3 | 2 of 27 | 1 of 30 | 2 of 31 | 1 of 10 |
| Nausea | Gastrointestinal disorders | 0 of 6 | 0 of 3 | 0 of 27 | 1 of 30 | 3 of 31 | 1 of 10 |
| Muscular weakness | Musculoskeletal and connective tissue disorders | 0 of 6 | 0 of 3 | 1 of 27 | 1 of 30 | 3 of 31 | 0 of 10 |
| Aphasia | Nervous system disorders | 0 of 6 | 0 of 3 | 1 of 27 | 1 of 30 | 2 of 31 | 1 of 10 |
| Hallucination | Psychiatric disorders | 1 of 6 | 0 of 3 | 0 of 27 | 2 of 30 | 1 of 31 | 1 of 10 |
| Hypertension | Vascular disorders | 0 of 6 | 0 of 3 | 3 of 27 | 1 of 30 | 1 of 31 | 0 of 10 |
| Urinary tract infection | Infections and infestations | 1 of 6 | 0 of 3 | 0 of 27 | 0 of 30 | 3 of 31 | 0 of 10 |
| Ataxia | Nervous system disorders | 0 of 6 | 0 of 3 | 0 of 27 | 1 of 30 | 1 of 31 | 2 of 10 |
| Hemiparesis | Nervous system disorders | 0 of 6 | 0 of 3 | 2 of 27 | 1 of 30 | 1 of 31 | 0 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Part 1 Cohort 1 | Part 1 Cohort 2 | Part 1 MTD + Dose Expansion Cohort | Part 2 Cohort | Part 3 Cohort 1 | Part 3 Cohort 2 |
|---|---|---|---|---|---|---|---|
| Fatigue | General disorders | 3 of 6 | 2 of 3 | 20 of 27 | 20 of 30 | 24 of 31 | 9 of 10 |
| Nausea | Gastrointestinal disorders | 4 of 6 | 2 of 3 | 17 of 27 | 11 of 30 | 13 of 31 | 6 of 10 |
| Vomiting | Gastrointestinal disorders | 2 of 6 | 1 of 3 | 16 of 27 | 10 of 30 | 16 of 31 | 6 of 10 |
| Headache | Nervous system disorders | 4 of 6 | 3 of 3 | 12 of 27 | 14 of 30 | 13 of 31 | 5 of 10 |
| Hallucination | Psychiatric disorders | 0 of 6 | 0 of 3 | 12 of 27 | 12 of 30 | 19 of 31 | 6 of 10 |
| Confusional state | Psychiatric disorders | 1 of 6 | 0 of 3 | 7 of 27 | 7 of 30 | 16 of 31 | 7 of 10 |
| Dizziness | Nervous system disorders | 1 of 6 | 1 of 3 | 8 of 27 | 5 of 30 | 12 of 31 | 4 of 10 |
| Gait disturbance | General disorders | 0 of 6 | 1 of 3 | 4 of 27 | 5 of 30 | 15 of 31 | 5 of 10 |
| Diarrhoea | Gastrointestinal disorders | 1 of 6 | 1 of 3 | 8 of 27 | 7 of 30 | 10 of 31 | 2 of 10 |
| Fall | Injury, poisoning and procedural complications | 3 of 6 | 0 of 3 | 7 of 27 | 4 of 30 | 12 of 31 | 3 of 10 |
Serious events with the highest arm-level rate: encephalopathy (100.0%), headache (100.0%), convulsion (33.3%), pneumonia (20.0%), ataxia (20.0%).
The registry lists serious adverse events by cohort, including the number at risk and the number affected. For example, Part 1 Cohort 1 lists 6 participants at risk and 1 affected; Part 1 Cohort 2 lists 3 at risk and 0 affected; and the Part 1 MTD + Dose Expansion Cohort lists 27 at risk and 12 affected. Part 2 lists 30 at risk and 10 affected. Part 3 Cohort 1 lists 31 at risk and 14 affected, while Part 3 Cohort 2 lists 10 at risk and 5 affected. The Part 4 cohort counts are also reported separately, with small at-risk counts in several cohorts.
These are cohort-level counts, not a randomized comparison. Cohort size and treatment context vary, so the figures should be read as descriptive listings rather than evidence that one regimen has a higher or lower risk than another. The registry’s top serious-event terms include encephalopathy and headache, each listed as 100.0%, followed by convulsion at 33.3%, pneumonia and ataxia at 20.0%, and dysphagia at 16.7%. The denominator and method used for those term percentages are not reported in the registry record, so they should not be converted into participant counts.
Serious adverse events are distinct from the separately listed other adverse events. The affected counts do not by themselves convey severity grades, duration, attribution to treatment, or whether events overlapped within participants. The registry also lists deaths by cohort, but these counts should not be treated as the primary OS analysis result.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a completed, multicenter, open-label Phase 1/2 study with enrollment of 121 and several distinct study parts. It identifies the primary endpoint as OS among all treated participants in Part 3 and defines the endpoint and censoring rule. It also documents cohort-specific serious adverse event counts and several serious-event terms.
Those details do not provide the numerical primary endpoint result. The median OS and its 95% confidence interval are not reported in the registry record. There is also no reported hazard ratio, p-value, or randomized comparison. Accordingly, the record does not quantify the survival experience with the precision needed to characterize its magnitude, and it does not establish a treatment contrast against a control group.
More generally, an observed outcome in a single-group study is descriptive of the participants followed in that group. It cannot by itself show what would have happened to comparable participants under a different treatment. The different parts of this study should not be treated as randomized arms, because the registry identifies a single-group model and no allocation to a like-for-like control comparison.
The safety counts similarly describe reported events within cohorts. They do not provide a randomized safety comparison or, on their own, establish the cause of an event. The registry record does not give all details needed to assess event attribution, duration, or overlap. Its list of adverse-event outcomes also does not replace the absent numerical OS result.
The appropriate statistical reading is therefore limited: the study’s design, endpoint definition, target population, and some safety counts are documented, while the primary survival estimate and key analysis details are not reported in the registry record. No conclusion about a treatment effect should be drawn from the enrollment total, endpoint definition, or safety listings alone.
13. Why This Trial Matters Statistically
This study illustrates why the design and the endpoint population matter as much as the endpoint name. The registry identifies OS in Part 3 as the primary outcome, but the trial includes several different parts: combination treatment, single-agent treatment, enteral administration, and repeat-dose pharmacokinetics. Treating all of these as one interchangeable group would obscure which participants the primary endpoint is meant to describe.
It also highlights a distinction between a time-to-event endpoint definition and a reported result. The record explains when OS begins, what event counts, and how participants alive at last follow-up are censored. Yet it does not report the median or confidence interval. A well-defined endpoint is important, but without its numerical estimate and precision, readers cannot judge the observed survival summary.
The single-group design has important interpretive consequences. A cohort’s observed survival can describe the experience of its participants, but a randomized comparator is not identified. As a result, the record does not supply a like-for-like basis for estimating a treatment difference. This distinction prevents descriptive outcomes from being overstated as comparative evidence.
The safety listing offers another statistical lesson: counts from cohorts of different sizes and treatment contexts are not automatically comparable. Serious adverse-event figures need to be read with their denominators and cohort structure in mind. Percentages for listed event terms also require an understood denominator; that denominator is not reported in the registry record.
Finally, the record shows why an analysis plan and complete reporting are essential to interpretation. Multiplicity, interim analyses, detailed missing-data handling, and the primary endpoint analysis are not reported in the registry record. These omissions limit what can be concluded, even when study status and an endpoint definition are available.
14. 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 limitation for statistical interpretation is that the primary OS estimate and its 95% confidence interval are not reported in the registry record. The record names the endpoint and its population but does not provide the numerical result, the number of treated participants in the Part 3 analysis, or endpoint follow-up details beyond assessment up to approximately 42 weeks.
The study is described as single-group, open-label, and without allocation. It therefore does not provide a randomized control comparison. The several study parts represent different treatment settings and cannot be assumed to be directly comparable. The record does not report adjustments for differences between cohorts or a comparative analysis.
Safety results are shown by cohort, but the listing does not provide enough information to interpret event attribution, timing, duration, or overlap. The denominator and method for the listed serious-event term percentages are not reported in the registry record. The cohort death counts are not a substitute for the primary endpoint analysis.
The registry record does not report the statistical analysis plan, multiplicity handling, interim-analysis approach, sample-size justification, or detailed missing-data procedures. It also does not contain analysis entries. These gaps prevent assessment of the planned-versus-reported analysis and the robustness of the primary endpoint result.
Overall enrollment of 121 does not establish the size of the Part 3 treated analysis population. The registry record does not report whether every enrolled participant contributed to the primary endpoint analysis or explain any exclusions. Conclusions should therefore remain limited to the study structure and the specific descriptive safety figures recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Stage 1: Marizomib + Bevacizumab in WHO Gr IV GBM; Stage 2: Marizomib Alone; Stage 3: Combination of Marizomib and Bevacizumab — NCT02330562.
- Registry record last updated 2022-06-08; status last verified 2022-05.
- Results first posted 2022-06-08.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
This completed multicenter, open-label Phase 1/2 study evaluated MRZ alone and in combination with BEV across several parts in people with WHO Grade IV malignant glioma. The registry lists enrollment of 121, a single-group model, allocation not applicable, and no masking. The primary outcome was OS among all treated participants in Part 3, defined from first study-drug dose to death from any cause, with participants alive censored at last follow-up.
The registry record does not report the numerical median OS or its 95% confidence interval, and it contains no analysis entries. It also does not report a randomized comparator, multiplicity plan, interim analyses, or detailed missing-data methods. Cohort-specific serious adverse-event counts and listed event terms are available, but are descriptive and do not establish a comparative treatment effect.