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 Avelumab in Patients With Newly Diagnosed Glioblastoma Multiforme (NCT03047473), a na phase 2 study. The primary outcome is Safety and Tolerability.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03047473 |
| Phase | Phase 2 |
| Condition | Glioblastoma Multiforme of Brain |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 38 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Clinique Neuro-Outaouais |
| Results posted | Yes |
2. Clinical Question
Population
Patients with newly diagnosed glioblastoma multiforme. The registry record lists the condition as glioblastoma multiforme of the brain and records an enrollment of 38. The primary endpoint's population field is blank, so further eligibility details and the exact analysis population are not reported in the registry record.
Intervention
Avelumab was added to standard treatment with temozolomide and radiotherapy. The registry summary says avelumab began within 3 weeks of finishing radiotherapy, was given intravenously at 10mg/kg every 2 weeks with monthly temozolomide, and was planned to continue for 52 weeks.
Comparator
There was no separate control group. The study is described as a single-arm, open-label addition of avelumab to standard treatment, with no allocation and no masking. Outcomes therefore describe the enrolled group, rather than a randomized comparison between treatment strategies.
Primary question
How many participants had an avelumab-related adverse event that led to temporary or permanent discontinuation of avelumab over the course of 52 weeks? The registry also identifies autoimmune-origin adverse events of special interest and says adverse events were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. A numerical result for the primary endpoint is not reported in the registry record.
3. Trial Design
This completed phase 2 study was sponsored by Clinique Neuro-Outaouais. It enrolled 38 participants with newly diagnosed glioblastoma multiforme and used a single-group, open-label design. The registry lists allocation as not applicable and masking as none. Consequently, the study did not include a randomized control arm or blinded treatment assignment. Its structure is suited to describing safety and tolerability in the treated group, but does not by itself provide a randomized estimate of how outcomes compare with standard treatment alone.
The registry summary describes avelumab as an immune checkpoint inhibitor added to temozolomide and radiotherapy. Participants were to start avelumab within 3 weeks after completing radiotherapy. Avelumab was administered intravenously at 10mg/kg every 2 weeks alongside monthly temozolomide, with a planned total treatment duration of 52 weeks. The record identifies one arm, “Newly diagnosed GBM,” and characterizes it as the addition of avelumab to standard treatment.
The recorded start date is 2017-05-19, the primary completion date is 2021-08-09, and the study status is completed. These dates describe the registry record; they do not establish when each participant began or finished treatment. Additional details about eligibility criteria, treatment adherence, follow-up after treatment, protocol changes, and reasons participants may have stopped treatment are not reported in the registry record.
The design and listed primary endpoint focus on treatment tolerability, specifically adverse events attributed to avelumab that led to temporary or permanent discontinuation. The record also lists safety and tolerability as a secondary outcome. It does not report a treatment-effect comparison or a numerical result for the primary endpoint. The enrollment count and the adverse-event group count are different registry figures; the reasons for that difference 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.
Before assignment: 430 candidates were prescreened 38 were screened with 30 randomized The reasons for screen failure included: blood abnormality (n=3) withdrawal of consent (n=4) and low Karnofsky score (n=1)
Overall Study
| Stage | Newly Diagnosed GBM |
|---|---|
| STARTED | 30 |
| COMPLETED | 28 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Newly Diagnosed GBM |
|---|---|
| Lost to Follow-up | 2 |
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.
| Characteristic | Unit | Newly Diagnosed GBM |
|---|---|---|
| Participants analysed | 30 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 24 |
| Age, Categorical: >=65 years | Participants | 6 |
| Sex: Female, Male: Female | Participants | 13 |
| Sex: Female, Male: Male | Participants | 17 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 30 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: Canada | participants | 30 |
| MGMT methylation status: MGMT methylated | Participants | 10 |
| MGMT methylation status: MGMT unmethylated | Participants | 16 |
| MGMT methylation status: MGMT status unknown | Participants | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Safety and Tolerability, measured over over the course of the 52 weeks stsudy.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with an avelumab-related adverse event leading to permanent or temporary discontinuation of avelumab. Its timeframe is described as over the course of 52 weeks. This endpoint captures an event with a direct consequence for treatment: the participant stops avelumab, either temporarily or permanently, because of an adverse event considered related to avelumab.
As a count of participants, the endpoint is binary at the individual level: each participant either has at least one qualifying event or does not. Counting participants rather than every event helps express how many people experienced the specified treatment-discontinuation outcome. It does not, by itself, describe the number of events per participant, the severity of every event, or the duration of an interruption.
The registry says adverse events of special interest include those of autoimmune origin, and that grading follows the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. These details describe the intended safety assessment, but do not supply the endpoint result. A numerical count, proportion, uncertainty interval, definition of attribution procedures, and handling of participants without complete follow-up are not reported in the registry record.
This endpoint is relevant to a safety and tolerability study because discontinuation indicates that an adverse event affected the planned treatment course. It is not a measure of antitumor benefit, and it cannot establish whether avelumab caused an event simply because the event appears in an adverse-event listing. The registry record does not report a comparison group for interpreting the frequency of this outcome against another treatment strategy.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a completed, open-label, single-arm phase 2 study with an enrollment of 38. Its primary question concerns the number of participants with an avelumab-related adverse event leading to temporary or permanent discontinuation during the stated 52-week timeframe. However, the numerical result for that endpoint is not reported in the registry record. No primary endpoint estimate or confidence interval is available in the record to characterize its size or precision.
The adverse-event data are presented separately from the primary endpoint. For the “Newly Diagnosed GBM” group, the record lists 30 participants at risk, 27 participants with serious adverse events, 5 participants with other adverse events, and 26 deaths. Tumor progression is listed among the top serious adverse-event terms at 90.0%. These figures are registry safety listings; they are not a reported estimate for the primary endpoint of avelumab-related adverse events leading to discontinuation. The record does not identify the cause of each death or establish that the serious events or deaths were caused by avelumab.
The record does not report a randomized comparator, and the design is explicitly single-group with no allocation and no masking. Thus, the counts describe events recorded for this study group and cannot isolate the effect of adding avelumab from other influences, including the underlying disease, standard treatment, or the course of care. The registry record also does not report a statistical comparison with a control group.
Interpretation of the safety counts requires attention to denominators and definitions. The group lists 30 participants at risk, while the overall enrollment is 38; reasons for the different counts are not reported in the registry record. The denominator and event-counting details for the 90.0% serious-event term are not reported in the registry record, so that percentage should not be reinterpreted as a percentage of all enrolled participants. Nor does a count of participants with an event reveal how often events recurred or how long they lasted.
Overall, the posted data give selected safety counts but do not give the primary endpoint result or an inferential analysis. They therefore do not establish the frequency of the specified avelumab-related discontinuation outcome, its precision, or a causal treatment effect. The registry record does not report an efficacy result, so efficacy conclusions are not supported by the information recorded for this study.
9. Statistical Methods Explained
Because the study is single-group, its central descriptive task is to report what happened among participants receiving the study treatment regimen. For a binary participant-level endpoint, a complete result would normally identify the number who experienced the defined event and the relevant denominator. A proportion can help express frequency, while a confidence interval conveys uncertainty around an estimate. The registry record does not report a numerical primary endpoint result or its confidence interval, so neither the frequency nor its precision can be assessed from the record.
General statistical interpretation: a confidence interval describes a range of values compatible with the data under the analysis method and assumptions. It is not a guarantee that the true value lies in that interval, and it does not address sources of bias that the design cannot rule out. In a single-group study, a confidence interval around an event frequency would describe uncertainty within the observed group; it would not create a comparison with standard treatment alone. The registry record does not report a confidence interval or the method used to estimate one.
The primary outcome is a participant count, rather than a continuous measurement. For this kind of outcome, the distinction between people and events matters. One participant may experience more than one adverse event, but a participant-level count for the primary endpoint would count a person meeting the stated criterion rather than every event episode. The record does not report whether or how recurrent events were counted for the primary endpoint, or how treatment-relatedness was assessed.
General statistical interpretation: when event counts vary more than a simple probability model expects, over-dispersion can make standard errors too small if it is ignored. This can arise when participants differ in underlying risk or when events cluster within participants. Methods that account for such variation can yield more realistic uncertainty. The primary endpoint is described as a number of participants, but no model, dispersion parameter, or analysis method is reported in the registry record. There is therefore no basis for claiming that over-dispersion was assessed or that a particular model was used.
The safety listings include participants with serious adverse events, participants with other adverse events, deaths, and a serious-event term. These quantities answer different descriptive questions and should not be combined or substituted for the primary endpoint. Seriousness, attribution to treatment, and treatment discontinuation are distinct concepts. The record identifies the primary endpoint as avelumab-related events leading to discontinuation, while its adverse-event listing gives aggregate safety figures. It does not report participant-level overlap among these categories or the analysis rules for classifying them.
A single-group design has no concurrent randomized comparator. General statistical interpretation: randomization helps balance measured and unmeasured prognostic factors on average, so a between-group contrast can better support causal interpretation. Without that comparison, changes or events observed during follow-up cannot be assigned uniquely to the added treatment. This limitation is especially important for outcomes that may also occur because of the disease or background treatment. The registry lists tumor progression as a serious adverse-event term, but that listing does not establish a treatment cause.
The registry reports 38 enrolled participants and an adverse-event group with 30 at risk. These are distinct recorded counts, and the reason for the difference is not reported in the registry record. A denominator is necessary to interpret an event frequency, and the applicable denominator can vary by outcome and follow-up. The record does not specify how the risk set was determined, whether all enrolled participants were included in each safety analysis, or how incomplete observation was handled.
The sample-size planning description is an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it says that the effect to detect is a stated fraction of the observed effect. Such planning values are hypothetical design illustrations, not observed power and not outcomes of this single-group trial. The record does not report that these assumptions formed the study's own design or provide a sample-size justification for this trial. It also does not report the observed effect needed to interpret those illustrations as trial results.
The registry lists zero analyses. This means that an inferential analysis is not recorded there; it does not establish what analyses may have been performed outside the registry record. No statistical analysis plan, hypothesis test for the primary endpoint, confidence-interval method, covariate adjustment, or prespecified subgroup analysis is reported in the registry record. Accordingly, statistical conclusions should remain descriptive and limited to the posted counts.
10. Multiplicity, Missing Data and Analysis Populations
The record identifies safety and tolerability as the primary outcome and also lists safety and tolerability as a secondary outcome. It reports two outcome measures and zero analyses. The outcome descriptions do not provide a complete map of planned endpoints, hypotheses, or analysis decisions. A multiplicity strategy for handling several outcomes or repeated statistical tests is not reported in the registry record. Without that information, it is not possible to determine whether any inferential results were adjusted for multiple comparisons or how any such adjustment would affect interpretation.
Missing-data handling is also not reported in the registry record. The record does not describe how participants who stopped treatment, missed assessments, withdrew, or had incomplete adverse-event follow-up were handled in the primary endpoint calculation. It does not state whether the analysis used all enrolled participants, only participants who started avelumab, or another analysis population. The primary endpoint population field is blank.
The enrollment is 38, whereas the adverse-event group lists 30 participants at risk. The reason for this difference and the denominator used for the primary endpoint are not reported in the registry record. Without those details, an event count cannot be interpreted as a complete-case estimate, a treatment-exposure estimate, or an estimate for all enrolled participants. The registry record also does not report sensitivity analyses for missing or incomplete outcome data.
These omissions limit assessment of robustness and potential bias. They do not show that missing data or multiplicity affected the study results; they mean the registry record does not describe how those issues were addressed. The listed safety counts remain descriptive registry entries, not a substitute for a prespecified analysis plan or a reported primary endpoint analysis.
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 |
|---|---|---|---|
| Newly Diagnosed GBM | 27 | 30 | 90.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Newly Diagnosed GBM | 26 of 30 |
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 |
|---|---|
| Newly Diagnosed GBM | 5 of 30 |
Most frequent serious adverse event terms
| Event term | Organ system | Newly Diagnosed GBM |
|---|---|---|
| tumor progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 27 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Newly Diagnosed GBM |
|---|---|---|
| hepatic enzymes elevation | Hepatobiliary disorders | 5 of 30 |
Serious events with the highest arm-level rate: tumor progression (90.0%).
The safety listing for the “Newly Diagnosed GBM” group records 30 participants at risk, 27 participants with serious adverse events, 5 participants with other adverse events, and 26 deaths. It also lists tumor progression at 90.0% among the top serious adverse-event terms. These figures describe the safety information recorded for the group; they do not report the primary endpoint count of participants with an avelumab-related event leading to treatment discontinuation.
Serious adverse events are not necessarily treatment-related, and the primary endpoint specifically requires an event to be considered related to avelumab and to lead to temporary or permanent discontinuation. The registry does not report how many serious events met both of those conditions. It also does not report the cause of deaths, the denominator behind the 90.0% figure, or whether participants could contribute to more than one adverse-event category. The death count should therefore not be read as a count of deaths caused by avelumab.
Enrollment was 38, while the listed at-risk count is 30; why these counts differ is not reported in the registry record. The adverse-event figures should be read as recorded safety data with those denominator and attribution limits, rather than as evidence of a comparative treatment effect.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed, open-label, single-group phase 2 study evaluated adding avelumab to temozolomide and radiotherapy in patients with newly diagnosed glioblastoma multiforme. It identifies a safety-focused primary question: the number of participants whose avelumab-related adverse event led to temporary or permanent discontinuation over the stated 52-week timeframe. The record also includes selected adverse-event counts for the study group.
Those details do not establish the frequency of the primary endpoint. Its numerical result is not reported in the registry record. The record also does not report an uncertainty interval or an inferential analysis for that endpoint. The listed serious-event and death counts are not interchangeable with the primary endpoint and do not, on their own, indicate which events were attributed to avelumab or led to treatment discontinuation.
The design cannot estimate a randomized contrast between adding avelumab and not adding it because there is no separate control group. Observed events may reflect the underlying disease, background treatment, avelumab, or other factors; the registry record does not separate these explanations. The listed tumor progression term does not establish that avelumab caused progression, and the death count does not establish treatment-related mortality.
Nor does the registry record provide an efficacy result. A safety-focused endpoint and an adverse-event listing do not show whether the treatment regimen affected tumor outcomes or survival. Such conclusions are not supported by the recorded information. The record also does not report a complete account of outcome follow-up, missing-data handling, or the analysis population, further limiting interpretation of the posted counts.
The defensible reading is therefore narrow: the registry documents the study design, regimen, intended safety endpoint, and selected safety figures, but leaves the primary endpoint result and its statistical precision unreported. The observations should be interpreted descriptively, with no causal or comparative treatment conclusion drawn from the single-group record.
13. Why This Trial Matters Statistically
This trial raises a useful statistical distinction between a clearly stated safety question and a result that can be evaluated quantitatively. The endpoint is specific in its key elements: an adverse event must be considered related to avelumab and must lead to temporary or permanent discontinuation. Yet the numerical result for that endpoint is not reported in the registry record. Without the event count and its denominator, readers cannot assess its frequency, and without an uncertainty estimate they cannot assess its precision.
The design also makes the scope of inference important. A single-group study can document events occurring during a treatment regimen, but it does not provide a randomized estimate of how those events compare with an alternative. This matters when the record includes serious events such as tumor progression and deaths, which may have multiple possible explanations. Clear separation of event occurrence, seriousness, attribution, and treatment discontinuation is essential for interpreting safety records.
The difference between the overall enrollment of 38 and the safety group's 30 participants at risk highlights the importance of reporting analysis populations and denominators. The reason for that difference is not reported in the registry record. Denominator definitions, follow-up completeness, and missing-data handling are central to interpreting counts as event frequencies.
Finally, the registry's recorded absence of analyses leaves readers without an inferential account of the primary endpoint. That absence does not establish that no analysis was conducted elsewhere, but it means the registry record cannot support conclusions about statistical significance or precision. The study is therefore informative as a record of a safety-focused design and selected adverse-event listings, while its quantitative answer to the primary question remains unavailable in the registry record.
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 single-group, open-label design is the main limitation for causal interpretation. With no randomized comparator and no masking, the study cannot isolate the effect of adding avelumab from the effects of standard treatment, disease progression, or other influences. The record is useful for describing events in the treated group, but it does not support a like-for-like comparison with another treatment strategy.
The registry does not report the primary endpoint result, an uncertainty interval, or an inferential analysis. Although the endpoint is defined as avelumab-related adverse events leading to temporary or permanent discontinuation, the record does not state how relatedness was assessed or how discontinuations were classified. It also does not provide the analysis population or explain why 38 participants were enrolled while 30 are listed as at risk in the adverse-event group.
Further limitations include unreported missing-data procedures, follow-up completeness, and the denominator behind the serious-event term reported at 90.0%. The record does not report whether adverse-event categories overlap, the causes of deaths, or which events were considered treatment-related. The selected safety counts therefore cannot be treated as a complete analysis of the primary endpoint.
The study summary describes the treatment regimen and intended duration, but additional details about eligibility, adherence, protocol changes, and post-treatment follow-up are not reported in the registry record. The registry also does not report the study's statistical analysis plan or its sample-size justification. These limits concern what can be established from the registry record; they do not determine what analyses or information may exist elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Avelumab in Patients With Newly Diagnosed Glioblastoma Multiforme — NCT03047473.
- Registry record last updated 2025-05-25; status last verified 2025-05.
- Results first posted 2025-05-25.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a completed phase 2, open-label, single-group study of avelumab added to temozolomide and radiotherapy for newly diagnosed glioblastoma multiforme. Enrollment was 38. The study began on 2017-05-19 and reached primary completion on 2021-08-09; Clinique Neuro-Outaouais is listed as sponsor.
The primary endpoint was the number of participants with an avelumab-related adverse event leading to temporary or permanent discontinuation over the stated 52-week timeframe. The numerical primary endpoint result and an inferential analysis are not reported in the registry record. The adverse-event listing records 30 participants at risk, 27 with serious adverse events, 5 with other adverse events, and 26 deaths; tumor progression is listed among the top serious-event terms at 90.0%. These descriptive figures do not establish treatment causation or a comparison with a control group.