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 GEM STUDY: Radiation And Yervoy in Patients With Melanoma and Brain Metastases (NCT02115139), a na phase 2 study. The primary outcome is 1-year Survival Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02115139 |
| Phase | Phase 2 |
| Condition | Melanoma, Brain Metastases |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 58 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Grupo Español Multidisciplinar de Melanoma |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns patients with melanoma and brain metastases. The primary endpoint was specified for an efficacy cohort consisting of patients who fulfilled eligibility criteria and completed radiotherapy. The registry record does not report how many participants met that endpoint population definition.
Intervention
The treatment combined ipilimumab with whole-brain radiotherapy. The arm description specifies ipilimumab 3mg/Kg intravenously every 3 weeks for 4 cycles, with radiotherapy of 30 Gy in 10 fractions or a radiobiological equivalent schedule after sponsor approval. Radiation was to start between Cycle 1 Day 2 and Cycle 2 Day 1.
Comparator
There was no separate comparator group. This was a single-group study with no allocation to different arms, so its results cannot provide a randomized, like-for-like comparison against another treatment or against radiation alone.
Primary question
The primary endpoint asked what percentage of the specified efficacy cohort was alive at one year. The registry record describes the endpoint and a planned 95% confidence interval, but a numerical survival estimate and its interval are not reported in the registry record. Consequently, the record does not give a numerical answer to the primary question.
3. Trial Design
This was a phase 2, multicenter, single-group study of ipilimumab and radiation therapy in patients with melanoma and brain metastases. The registry lists an enrollment of 58 and a completed study status. The study began on 2014-04-04, with primary completion dated 2016-12-31. These dates and the completed status describe the registry record; they do not establish that every enrolled participant completed treatment or contributed to every endpoint.
The intervention description specifies ipilimumab 3mg/Kg intravenously every 3 weeks for 4 cycles. Whole-brain radiotherapy was specified as 30 Gy in 10 fractions, or a radiobiological equivalent schedule after sponsor approval, starting between Cycle 1 Day 2 and Cycle 2 Day 1. Although the study title emphasizes the combination, the registry lists ipilimumab as the intervention and describes radiation in the arm regimen.
Allocation is listed as not applicable, masking as none, and the model as single group. Thus, the design has no randomized control arm and no masking. A single-group result can describe outcomes observed among participants in the study, but cannot isolate the contribution of either treatment from the other or from other influences. The registry record does not report a protocol-specific sample-size justification, interim analysis plan, or detailed statistical analysis plan.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Ipilimumab |
|---|---|
| STARTED | 58 |
| COMPLETED | 51 |
| NOT COMPLETED | 7 |
Reasons for not completing this period:
| Reason | Ipilimumab |
|---|---|
| Protocol Violation | 1 |
| treatment discontinuation | 6 |
Analysis population for the primary outcome, as defined in the registry: Efficacy cohort, all patients that fulfill eligibility and completed the treatment with radiotherapy
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 | Ipilimumab |
|---|---|---|
| Participants analysed | 58 | |
| Age, Continuous | Years | 66 (36.8 to 84.5) |
| Sex: Female, Male: Female | Participants | 22 |
| Sex: Female, Male: Male | Participants | 36 |
| Region of Enrollment: Spain | Participants | 58 |
| Karnofsky performance status (KPS): 90-100 | Participants | 42 |
| Karnofsky performance status (KPS): 70-80 | Participants | 15 |
| Karnofsky performance status (KPS): Not evaluable (NE) | Participants | 1 |
| Barthel index: Lower than 15 | Participants | 2 |
| Barthel index: 15-20 | Participants | 56 |
| BRAF mutational status: Mutated | Participants | 20 |
| BRAF mutational status: Native | Participants | 30 |
| BRAF mutational status: Not evaluated (NE) | Participants | 8 |
| Number of previous treatment lines: No previous lines | Participants | 29 |
| Number of previous treatment lines: 1 previous line | Participants | 20 |
| Number of previous treatment lines: 2 or more previous lines | Participants | 9 |
| Number of brain metastasis: Single brain lesion | Participants | 14 |
| Number of brain metastasis: Multiple brain lesions | Participants | 43 |
| Number of brain metastasis: Not especified (NE) | Participants | 1 |
| Corticoid use: Yes | Participants | 25 |
| Corticoid use: No | Participants | 33 |
| Lactate dehydrogenase (LDH) blood levels: Levels higher than Upper limit normal (ULN) – Yes | Participants | 24 |
| Lactate dehydrogenase (LDH) blood levels: Levels higher than Upper limit normal (ULN) – No | Participants | 34 |
| Lactate dehydrogenase (LDH) blood levels: Levels higher than 1.5X Upper limit normal (ULN) – Yes | Participants | 9 |
| Lactate dehydrogenase (LDH) blood levels: Levels higher than 1.5X Upper limit normal (ULN) – No | Participants | 49 |
6. Primary Endpoint
The registry lists the primary outcome as 1-year Survival Rate, measured over From date of inclusion until the date of first documented date of death from any cause, assessed every 3 weeks during for the first 6 months, then every 3 months. Up to 1 year.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of patients alive at 1 year |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the one-year survival rate, defined as the percentage of patients alive at one year. The registry describes follow-up from inclusion until death from any cause, with assessments every 3 weeks during the first 6 months and then every 3 months, up to one year. It also describes assessments every cycle during treatment and every 3 months after treatment ended.
The endpoint is a fixed-time summary of survival status: it focuses on whether participants are alive at the specified time rather than on a particular tumor response. General statistical context: a fixed-time survival rate can give a clinically interpretable snapshot, while a confidence interval conveys uncertainty around the estimated rate. The registry lists a 95% confidence interval as the intended measure of dispersion, but the numerical rate, interval limits, and endpoint analysis results are not reported in the registry record.
The stated primary population was the efficacy cohort: patients who fulfilled eligibility criteria and completed treatment with radiotherapy. The number of participants in that cohort and the approach to participants whose one-year status was unavailable are not reported in the registry record. Therefore, the endpoint definition is available, but the posted information does not permit a reader to reconstruct its estimate or precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a primary endpoint and a planned follow-up period, but it does not report the primary one-year survival rate or its 95% confidence interval. Without those values, the size and precision of the primary endpoint estimate cannot be evaluated from the registry record. The record also does not report a p-value or a numerical result for the listed secondary outcomes.
The study enrolled 58 participants and used a single-group design. That design can document outcomes among participants receiving the specified combination, but it does not establish what outcomes would have occurred under a different treatment. In particular, there is no randomized comparison with radiation alone, ipilimumab alone, or another control in the registry record. Any observed outcome would therefore be descriptive of this study group, not a direct estimate of a treatment difference against a control group.
The listed secondary outcomes include progression-free survival, intracranial progression-free survival, extracranial progression-free survival, overall survival, response rate, adverse event rates, and dose delays, reductions, and treatment exposure. The registry record lists 10 outcome measures, but numerical findings for these outcomes are not reported in the registry record. No analyses are listed in the record. The absence of posted analysis results means that efficacy conclusions cannot be drawn from the outcome titles alone.
The primary endpoint population is described as patients who fulfilled eligibility and completed radiotherapy. That definition may differ from the full enrollment, but the number included in the efficacy cohort is not reported in the registry record. The record also does not give the number with available one-year follow-up, the handling of missing survival information, or details of any censoring rules. These omissions matter because an estimate based on a subset or on assumptions about unavailable follow-up may not have the same interpretation as a complete follow-up result.
General statistical context: a confidence interval represents uncertainty in an estimate under the assumptions of the analysis; it does not correct for lack of a comparator, missing outcome information, or potential selection into the analysis population. Here, the intended confidence interval is named, but its limits are not reported. Accordingly, neither the point estimate nor its precision can be assessed. The registry information supports a description of the study question, treatment schedule, and design, but not a numerical assessment of the primary or secondary clinical outcomes.
9. Statistical Methods Explained
What does the design allow?
This study is described as phase 2 and single group, with no allocation to separate treatment arms and no masking. General statistical context: a single-group study estimates outcomes within the group that received the study regimen. Without a concurrent comparator, the analysis cannot distinguish outcomes associated with the regimen from outcomes that might also occur because of disease characteristics, other care, participant selection, or the natural course of illness. Those are limits on interpretation, not evidence that any particular influence occurred in this study.
The registry record does not report a randomized comparison, and the study should not be read as if it had one. There is no like-for-like control group in the design. The listed enrollment is 58, but enrollment alone does not show how many participants were eligible for the primary endpoint population, completed radiotherapy, or had complete follow-up.
How should the survival endpoint be understood?
The primary endpoint is the percentage alive at one year, with death from any cause as the event of interest. Follow-up was described from inclusion, with assessments every 3 weeks during the first 6 months and every 3 months thereafter, up to one year. General statistical context: survival analyses account for the time until an event and may also account for participants whose event status is not observed through the full follow-up period. A fixed-time survival percentage communicates status at a chosen time, while a time-to-event curve can use information across follow-up.
The registry names a 95% confidence interval for the primary endpoint but does not report its estimate or interval limits. The statistical method used to calculate the interval, the handling of incomplete follow-up, and any censoring details are not reported in the registry record. These details affect how the estimate should be interpreted and how precisely it can be reproduced.
What does a confidence interval contribute?
General statistical context: a confidence interval describes sampling uncertainty around an estimate under a specified statistical method and its assumptions. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. An interval is not a guarantee that the true value lies within its particular limits, nor does it account automatically for bias, missing data, or the lack of a comparison group. Since the numerical interval is not reported in the registry record, the precision of the one-year survival estimate cannot be judged.
How should the planning illustration be read?
The registry record describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration is described in terms of total events using the Schoenfeld approach; other outcomes are expressed as participants per arm. These are planning assumptions, not a description of the actual single-group trial design. The numerical planning results and observed effect needed to assess them are not reported in the registry record.
General statistical context: sample-size calculations are conditional on assumptions about the effect to be detected, variability or event timing, allocation, and the chosen statistical method. They are planning tools, not evidence that a study had a particular probability of finding a result after data collection. A sample-size illustration should not be interpreted as observed power. It also cannot substitute for the trial's own documented design justification, which is not reported in the registry record.
What can the secondary outcomes add?
The record lists progression-free survival, intracranial and extracranial progression-free survival, overall survival, response rate, adverse event rates, and treatment exposure measures among its secondary outcomes. These outcomes cover disease progression, survival, response, and treatment experience, but their definitions, analysis methods, and numerical results are not reported in the registry record. The record lists 10 outcome measures and no analysis entries. Outcome names alone do not indicate whether an endpoint was analyzed, how it was analyzed, or what its result was.
General statistical context: progression-free survival combines a time component with a specified progression or death event definition, and response rates depend on defined response criteria and an analysis population. Without those definitions and results, one cannot compare estimates, assess uncertainty, or determine whether any apparent pattern is robust. The registry record does not report the detailed analysis plan needed to answer these questions.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary one-year survival endpoint and several secondary outcomes: progression-free survival, intracranial progression-free survival, extracranial progression-free survival, overall survival, response rate, adverse event rates, and dose delays, reductions, and treatment exposure. It lists 10 outcome measures, but no analysis entries. Numerical results for the listed outcomes and a multiplicity strategy are not reported in the registry record.
General statistical context: when multiple outcomes are tested, the chance of at least one apparently unusual result can increase if each is interpreted as a separate confirmatory test. Researchers may prespecify a hierarchy, adjust significance thresholds, or treat secondary findings as exploratory. Which approach was intended for this study is not reported in the registry record. Without the analysis plan and reported results, the role of any secondary outcome cannot be determined.
The primary endpoint population is defined as eligible patients who completed radiotherapy. The record does not report the size of this cohort, the number with one-year status available, or how missing data were handled. It also does not describe an intention-to-treat analysis population or specify how participants who did not complete radiotherapy were treated in the analysis. The number enrolled cannot be assumed to equal the number analyzed.
General statistical context: missing follow-up can affect an estimate if participants without observed outcomes differ from those with complete data. The direction and size of any such effect cannot be inferred without information about missingness and the analysis method. The record also does not report censoring rules for survival analyses. These omissions limit reproducibility and interpretation, even though the endpoint schedule and intended efficacy population are described.
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 |
|---|---|---|---|
| Ipilimumab | 33 | 58 | 56.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Ipilimumab | 40 of 58 |
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 |
|---|---|
| Ipilimumab | 57 of 58 |
Most frequent serious adverse event terms
| Event term | Organ system | Ipilimumab |
|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 6 of 58 |
| Malaise | General disorders | 4 of 58 |
| Headache | Nervous system disorders | 3 of 58 |
| Cognitive disturbance | Nervous system disorders | 2 of 58 |
| Fever | General disorders | 2 of 58 |
| Lung infection | Infections and infestations | 2 of 58 |
| Seizures | Nervous system disorders | 2 of 58 |
| Thromboembolic event | Vascular disorders | 2 of 58 |
| Urinary tract infection | Infections and infestations | 2 of 58 |
| Vomiting | Gastrointestinal disorders | 2 of 58 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ipilimumab |
|---|---|---|
| Fatigue | General disorders | 28 of 58 |
| Headache | Nervous system disorders | 23 of 58 |
| Nausea | Gastrointestinal disorders | 16 of 58 |
| Anorexia | Metabolism and nutrition disorders | 15 of 58 |
| Diarrhoea | Gastrointestinal disorders | 14 of 58 |
| Pruritus | Skin and subcutaneous tissue disorders | 13 of 58 |
| Alopecia | Skin and subcutaneous tissue disorders | 9 of 58 |
| Vomiting | Gastrointestinal disorders | 9 of 58 |
| Dizziness | Nervous system disorders | 7 of 58 |
| Fever | General disorders | 7 of 58 |
Serious events with the highest arm-level rate: diarrhoea (10.3%), malaise (6.9%), headache (5.2%), cognitive disturbance (3.4%), fever (3.4%).
The registry lists 58 participants at risk for serious adverse events, with serious adverse events recorded for 33. It also lists 58 participants at risk for other adverse events, with other adverse events recorded for 57. These are separate registry summaries; the record does not explain whether participants could be counted in both categories or provide event-level timing and duration.
The serious adverse event terms listed most prominently are diarrhoea (10.3%), malaise (6.9%), headache (5.2%), cognitive disturbance (3.4%), fever (3.4%), and lung infection (3.4%). The registry record does not provide the denominator or further calculation details for these term-specific percentages. A listed percentage should therefore be read as a registry-reported figure, not converted into a count or interpreted as a comparison between treatments.
The record reports 40 deaths, but does not specify their timing, causes, relationship to treatment, or how they relate to one-year endpoint follow-up. These safety summaries describe events reported in the study group; a single-group study cannot establish comparative safety. The registry record does not provide enough detail to attribute an event to ipilimumab, radiation, or another cause.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a completed phase 2, single-group study examined ipilimumab given with whole-brain radiotherapy in patients with melanoma and brain metastases. It specifies a primary question about the percentage of an efficacy cohort alive at one year, and it describes the intended regimen and follow-up schedule. The posted record does not report the numerical primary endpoint result or its 95% confidence interval.
That missing result is decisive for statistical interpretation: the survival rate and its precision cannot be assessed from the registry record. The record also does not report numerical results for its listed secondary outcomes. Therefore, the outcome names, enrollment, and treatment schedule do not by themselves establish the magnitude or reliability of any clinical outcome.
The single-group design also sets a separate limit. Even if numerical outcomes were available, this design would describe the study group rather than provide a randomized comparison with another regimen. It cannot isolate the separate contributions of ipilimumab and radiation, and it cannot show what would have happened to a comparable group receiving a different treatment.
General statistical context: an estimate and its uncertainty address only some parts of a study's evidence. Design, analysis population, completeness of follow-up, and the possibility of selection or other influences also matter. Here, the analysis population size, missing-data handling, and detailed analysis methods are not reported in the registry record. The appropriate reading is therefore limited to the documented study design, outcome definitions, and adverse-event summaries. The registry information does not support a conclusion about comparative treatment effects.
13. Why This Trial Matters Statistically
This study is statistically notable because its primary question is defined as a one-year survival rate, while the design is single group. A fixed-time survival endpoint is straightforward to state, but its interpretation depends on who entered the endpoint analysis and how follow-up was handled. The registry record identifies the intended efficacy cohort and assessment schedule, yet does not report the cohort size, numerical estimate, confidence interval, or missing-data approach.
The combination regimen also makes the absence of a comparator important. The study evaluates ipilimumab alongside radiation, so a single-group outcome cannot separate the contribution of either component. A randomized comparison would address a different question; the registry record does not describe one. This distinction helps keep descriptive outcomes separate from estimates of comparative effect.
The record includes a list of secondary outcomes spanning progression, survival, response, safety, and treatment exposure. Such breadth can be useful for describing different aspects of a trial, but interpretation depends on prespecified methods and complete reporting. The registry record lists no analysis entries, and it does not report a multiplicity strategy. Thus, the presence of many outcome names should not be mistaken for a set of reported findings.
Finally, the safety summary gives counts and selected serious-event terms, while the record provides limited information about event timing, attribution, and analysis. These figures are descriptive of this trial group. The statistical importance of the study lies in recognizing the difference between a defined clinical question and a reported, interpretable estimate: the former is recorded, while the latter is not reported 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 registry record does not report the primary one-year survival estimate, its 95% confidence interval, or numerical findings for the secondary outcomes. It also does not report a detailed statistical analysis plan, the protocol-specific sample-size justification, interim analyses, missing-data methods, or censoring rules. These gaps prevent assessment of the planned analysis and reproduction of the primary result.
The stated primary population is restricted to eligible patients who completed radiotherapy, but the number meeting that definition is not reported. The record does not state how participants who did not complete treatment or lacked follow-up were handled. Enrollment of 58 should not be treated as the analysis population for every endpoint.
The single-group design has no randomized control, and masking is listed as none. As a result, outcomes cannot be directly compared with a control group, and the contributions of ipilimumab and radiation cannot be distinguished. The registry record also does not give detailed definitions for the listed secondary outcomes or explain the basis for the term-specific adverse-event percentages.
The record lists 40 deaths but does not describe their timing, cause, treatment relationship, or connection to the one-year survival analysis. Adverse-event counts and terms are therefore descriptive and do not establish attribution or comparative risk. These limitations concern what can be concluded from the registry record; they do not determine what may be available in other study documents.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: GEM STUDY: Radiation And Yervoy in Patients With Melanoma and Brain Metastases — NCT02115139.
- Registry record last updated 2022-11-08; status last verified 2022-10.
- Results first posted 2021-07-01.
- 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
The registry describes a completed, multicenter, phase 2, single-group study of ipilimumab with whole-brain radiotherapy in patients with melanoma and brain metastases. Enrollment is listed as 58. The regimen specifies ipilimumab 3mg/Kg intravenously every 3 weeks for 4 cycles and radiotherapy of 30 Gy in 10 fractions, with a specified start window.
The primary endpoint was the percentage alive at one year in an efficacy cohort of eligible patients who completed radiotherapy. The registry describes a 95% confidence interval and a follow-up schedule, but the numerical endpoint estimate and interval are not reported in the registry record. Secondary outcomes are listed without numerical findings, and no analysis entries are listed.
Safety summaries list 33 of 58 participants with serious adverse events, 57 of 58 with other adverse events, and 40 deaths. The design has no randomized comparator, so the record describes a treatment group rather than a comparative effect.