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 Study to Compare the Effect of Ipilimumab Retreatment With That of Chemotherapy in Advanced Melanoma (NCT01709162), a randomized phase 2 study. The primary outcome is Overall Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01709162 |
| Phase | Phase 2 |
| Condition | Melanoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 31 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Bristol-Myers Squibb |
| Results posted | Yes |
2. Clinical Question
The study asked whether retreatment with ipilimumab could affect overall survival in people with advanced melanoma whose disease had progressed after they initially achieved disease control with ipilimumab. It compared ipilimumab retreatment with chemotherapy selected by the investigator. The registry identifies the study as randomized, open-label, multicenter, and phase II.
The primary outcome was overall survival, measured from randomization until death or the last date the participant was known to be alive. The record describes the outcome population as all randomized participants and specifies assessment up to 15.6 months. The posted arm summaries report a median and full range for each group, but the record does not report a sponsor hazard ratio or another usable estimate of the treatment comparison.
Population
People with advanced melanoma who progressed after initially achieving disease control with ipilimumab. The primary outcome population is described as all participants who were randomized.
Intervention
Ipilimumab, 3 mg/kg, by intravenous infusion every 3 weeks for a total of 4 doses, or until disease progression, unacceptable toxicity, or withdrawal of consent.
Comparator
Chemotherapy chosen by the investigator and administered according to package instructions.
Primary question
How did overall survival, measured from randomization to death or last known alive date, compare between the treatment groups?
The posted medians are descriptive arm summaries. Without an estimable sponsor-reported comparison, they do not establish the size or precision of a treatment difference. The registry record also does not report the reason the study was terminated.
3. Trial Design
This was a randomized, open-label, parallel-group phase II study sponsored by Bristol-Myers Squibb. It enrolled 31 participants, and its status is listed as terminated. The recorded study start is 2013-03 and the primary completion is 2014-07. The registry record does not state why the trial was terminated.
One group received ipilimumab, 3 mg/kg, as an intravenous infusion every 3 weeks for a total of 4 doses, unless disease progression, unacceptable toxicity, or withdrawal of consent occurred earlier. The comparator was chemotherapy selected by the investigator and administered per package instructions. Because the study was open-label, treatment assignment was not masked according to the registry.
The primary outcome was overall survival in all randomized participants. The posted arm summaries list 18 participants for ipilimumab and 5 for chemotherapy. These outcome populations do not account for the registry's enrollment figure of 31, and the record does not explain the difference. Safety summaries use at-risk counts of 18 for ipilimumab and 4 for chemotherapy. The record does not explain the difference between the chemotherapy outcome and safety denominators.
The registry lists Disease Control Rate and Best Overall Response Rate as secondary outcomes. It reports two secondary outcomes, but numerical results for those outcomes are not reported in the registry record. The protocol’s sample-size justification, intended analysis plan, and any interim analyses are not reported in the registry record. The trial's randomized design supports a planned comparison, but the small posted outcome groups and the absence of an estimable comparative result limit what can be concluded from the available summaries.
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: A total of 31 participants were enrolled. Of the 23 who were randomized, 22 received treatment .
Overall Study
| Stage | Ipilimumab, 3 mg/kg | Chemotherapy |
|---|---|---|
| STARTED | 18 | 5 |
| Received Treatment | 18 | 4 |
| Still Receiving Treatment | 0 | 0 |
| COMPLETED | 12 | 0 |
| NOT COMPLETED | 6 | 5 |
Reasons for not completing this period:
| Reason | Ipilimumab, 3 mg/kg | Chemotherapy |
|---|---|---|
| Disease progression | 3 | 3 |
| Study drug toxicity | 2 | 0 |
| Administrative reason by sponsor | 0 | 1 |
| Other | 1 | 0 |
| Withdrawal by Subject | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: All participants who were randomized
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.
Population: All participants who were randomized
| Characteristic | Unit | Ipilimumab, 3 mg/kg | Chemotherapy | Total |
|---|---|---|---|---|
| Participants analysed | 18 | 5 | 23 | |
| Age, Continuous | Years | 62.3 (SD 11.38) | 64.2 (SD 4.32) | 62.7 (SD 10.20) |
| Sex: Female, Male: Female | Participants | 6 | 1 | 7 |
| Sex: Female, Male: Male | Participants | 12 | 4 | 16 |
| Race/Ethnicity, Customized: White | Participants | 18 | 5 | 23 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status: 0 | Participants | 13 | 5 | 18 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status: 1 | Participants | 5 | 0 | 5 |
| Disease Stage at Study Entry: Stage III | Participants | 1 | 1 | 2 |
| Disease Stage at Study Entry: Stage IV | Participants | 17 | 4 | 21 |
| Objective Response to Prior Ipilimumab Treatment: Complete response/Partial response | Participants | 6 | 0 | 6 |
| Objective Response to Prior Ipilimumab Treatment: Stable disease | Participants | 12 | 5 | 17 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Survival, measured over From randomization to death or last known alive date, assessed up to 15.6 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | Months |
| Endpoint classification | Time-to-Event Analysis |
Overall survival measures the time from randomization until death. For a participant who has not died, the record defines the endpoint as censored at the last contact when the participant was known to be alive. The primary outcome is stated for all randomized participants and was assessed up to 15.6 months.
Time to death is used because it captures how long participants remain alive after assignment to a study group, without requiring a particular cause of death to be assigned. Censoring allows participants with no recorded death by their last known contact to contribute information up to that point; it does not mean that their later survival time is known. This is a general explanation of time-to-event outcomes, not a claim about additional analysis procedures used in this trial.
The registry reports a median overall survival of 6.3 months for ipilimumab, 3 mg/kg, with a full range of 3.2 to 15.6 months. For chemotherapy, it reports a median of 3.1 months with a full range of 0.0 to 8.6 months. The ranges describe the reported spread of observed times, not the uncertainty around each median. Confidence intervals for the medians are not reported in the registry record.
These arm summaries do not alone quantify the comparative treatment effect. A median difference is not a substitute for a time-to-event comparison that accounts for the timing of events and censoring. The registry record does not report an estimable sponsor hazard ratio or another comparative estimate for overall survival.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted overall-survival summaries are a median of 6.3 months, with a full range of 3.2 to 15.6 months, for ipilimumab, 3 mg/kg, and a median of 3.1 months, with a full range of 0.0 to 8.6 months, for chemotherapy. The corresponding posted outcome group sizes are 18 and 5. These are descriptive statistics for each arm; they do not by themselves establish the size, direction, or precision of a treatment effect.
The registry record does not report a sponsor hazard ratio, confidence interval, or p-value for the overall-survival comparison. It also flags the two-arm comparison as not estimable from the available median-time outcome values. As a result, the medians should not be read as a complete comparative analysis. In a time-to-event setting, the timing of events and the censoring of participants who are last known alive contribute to the comparison. The arm medians and ranges do not show all of that information.
The ranges should not be mistaken for confidence intervals. They describe the full range of posted times; they do not express how uncertain the median estimate is. No confidence intervals for the medians are reported in the registry record. The record also does not provide participant-level event times, numbers of deaths, or a posted survival curve in the registry record described for this analysis.
The registry reports enrollment of 31, but the arm-specific primary-outcome counts are 18 and 5. The record does not explain why the outcome counts do not account for enrollment. Safety summaries list at-risk counts of 18 and 4, so those denominators also differ from the posted primary-outcome chemotherapy count. These are reporting and interpretation limitations; they do not establish why participants are absent from a particular summary.
The study is listed as terminated, but the reason for termination is not reported in the registry record. The registry names Disease Control Rate and Best Overall Response Rate as secondary outcomes, but numerical results for them are not reported. The available information therefore supports a description of the posted survival summaries and their limitations, rather than a firm conclusion about the comparative survival effect.
9. Statistical Methods Explained
What does a median overall-survival value mean?
Overall survival is a time-to-event outcome. Its event is death, and the time origin in this study is randomization. A median is a summary of the survival distribution: it identifies the time at which the estimated survival experience reaches its midpoint. The registry reports median values for each arm, but it does not report confidence intervals for those medians.
The posted median is not an average survival time, and it does not mean that every participant in the group survived for that length of time. It is also not a treatment-effect estimate. Comparing arm medians can be informative descriptively, but the medians alone do not convey the event-time pattern, censoring, or uncertainty needed to interpret a time-to-event contrast.
How does censoring work?
The registry defines overall survival as time from randomization to death. If a participant has not died, the observation is censored at the last contact when the participant was known to be alive. In general, censoring means that the exact time to the event is not observed, while the participant contributes information through the last known time. It is not evidence that the participant had no event after that contact.
The registry's endpoint definition explains the censoring rule, but the record does not report detailed censoring counts or the individual timing of events. It also does not report the specific statistical procedure used to estimate the medians or compare the arms. Methods such as survival curves or hazard models are general tools for time-to-event analysis; their use in this trial cannot be inferred from the endpoint definition alone.
What can be learned from the reported ranges?
The full range for the ipilimumab group is 3.2 to 15.6 months, and the full range for chemotherapy is 0.0 to 8.6 months. A range describes the lowest and highest posted values. It does not show how observations are distributed between those endpoints and is not a measure of precision. A confidence interval serves a different purpose: it describes uncertainty around an estimate under a statistical method. Such intervals for the medians are not reported in the registry record.
Why is there no comparative estimate?
The registry record describes the primary outcome as median time and indicates that values are missing or not estimable for a two-arm comparison. It does not report a sponsor hazard ratio for overall survival. Without a posted comparative estimate and its uncertainty, the arm-level medians cannot be converted into a complete inferential result. No unadjusted recalculation is reported for this endpoint. A recalculation from arm summaries would not replace the sponsor's analysis if the registry had reported one.
What do the planning assumptions mean?
The registry's stated sample-size assumptions describe a planning illustration, not the trial's own design justification and not observed power. The assumptions specify a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. For time-to-event planning, the stated approach uses the total number of events under Schoenfeld. These are general planning concepts; they do not establish that the trial was planned or conducted using those assumptions.
Planning illustrations ask how much information might be needed under stated assumptions. They do not report how much power the completed study achieved. The protocol's sample-size justification and the statistical plan are not reported in the registry record. Because a comparative overall-survival estimate is not available, the posted information does not support treating a planning calculation as evidence for or against a treatment effect.
Why can over-dispersion matter in general?
Over-dispersion is a general concern for count outcomes when observed variation exceeds what a chosen statistical model expects. It can make standard errors too small if the analysis does not account for the extra variability. It is not a reported feature of this trial's primary endpoint, which is time to death, and the registry record does not describe an over-dispersion analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies overall survival as the primary outcome and lists Disease Control Rate and Best Overall Response Rate as secondary outcomes. It also reports four outcome measures and no posted analyses in the registry record described for this record. Numerical results for the named secondary outcomes are not reported in the registry record.
When a study evaluates multiple outcomes or multiple comparisons, multiplicity can arise: the chance of at least one apparently unusual result can increase if many statistical tests are considered without an appropriate plan. This is a general statistical issue, not a statement that the trial made a particular adjustment or conducted a particular set of tests. The registry record does not report a multiplicity strategy, a hierarchy among outcomes, or an adjustment for multiple testing.
The primary outcome population is described as all randomized participants, but the posted arm counts are 18 for ipilimumab and 5 for chemotherapy, while enrollment is 31. The record does not explain this accounting. It also does not report the number of deaths, the amount or pattern of missing outcome information, or how participants with incomplete follow-up were handled beyond the stated censoring definition. The chemotherapy safety at-risk count is 4, distinct from its primary-outcome count of 5; the reason is not reported.
The registry record does not report the protocol's analysis populations, any intention-to-treat specification beyond the primary population description, or methods for handling missing data beyond censoring participants at their last known alive date. It also does not report interim analyses or a statistical analysis plan. These absences limit assessment of whether the posted results follow a prespecified analysis strategy and how selective reporting or incomplete follow-up may affect interpretation.
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, 3 mg/kg | 7 | 18 | 38.9% |
| Chemotherapy | 0 | 4 | 0.0% |
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, 3 mg/kg | 15 of 18 |
| Chemotherapy | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Ipilimumab, 3 mg/kg | Chemotherapy |
|---|---|---|---|
| General physical health deterioration | General disorders | 2 of 18 | 0 of 4 |
| Depression | Psychiatric disorders | 1 of 18 | 0 of 4 |
| Orthostatic hypotension | Vascular disorders | 1 of 18 | 0 of 4 |
| Pancreatitis acute | Gastrointestinal disorders | 1 of 18 | 0 of 4 |
| Anaemia | Blood and lymphatic system disorders | 1 of 18 | 0 of 4 |
| Diarrhoea | Gastrointestinal disorders | 1 of 18 | 0 of 4 |
| Syncope | Nervous system disorders | 1 of 18 | 0 of 4 |
| Pneumonia | Infections and infestations | 1 of 18 | 0 of 4 |
| Myopathy | Musculoskeletal and connective tissue disorders | 1 of 18 | 0 of 4 |
| Colitis | Gastrointestinal disorders | 1 of 18 | 0 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ipilimumab, 3 mg/kg | Chemotherapy |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 6 of 18 | 0 of 4 |
| Fatigue | General disorders | 4 of 18 | 2 of 4 |
| Asthenia | General disorders | 3 of 18 | 1 of 4 |
| Pruritus | Skin and subcutaneous tissue disorders | 3 of 18 | 1 of 4 |
| Anaemia | Blood and lymphatic system disorders | 3 of 18 | 0 of 4 |
| Rash | Skin and subcutaneous tissue disorders | 2 of 18 | 1 of 4 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 2 of 18 | 1 of 4 |
| Nausea | Gastrointestinal disorders | 3 of 18 | 0 of 4 |
| Decreased appetite | Metabolism and nutrition disorders | 2 of 18 | 0 of 4 |
| Hyponatraemia | Metabolism and nutrition disorders | 2 of 18 | 0 of 4 |
Serious events with the highest arm-level rate: general physical health deterioration (11.1%), depression (5.6%), orthostatic hypotension (5.6%), pancreatitis acute (5.6%), anaemia (5.6%).
The safety summaries report serious adverse events affecting 7 of 18 participants at risk in the ipilimumab group and 0 of 4 participants at risk in the chemotherapy group. Other adverse events are reported for 15 of 18 at risk in the ipilimumab group and 4 of 4 at risk in the chemotherapy group. These are counts and denominators as posted; the safety denominators are not the same as the chemotherapy primary-outcome count.
The serious-event terms with reported percentages include general physical health deterioration at 11.1%, and depression, orthostatic hypotension, acute pancreatitis, anaemia, and diarrhoea at 5.6% each. These listed terms should be read as registry-reported event frequencies, not as a full description of event severity, duration, recurrence, or causal relationship to treatment. The record does not report deaths in the safety summary.
Safety counts are descriptive. Differences in group size and the limited at-risk counts, particularly for chemotherapy, make simple comparisons difficult to interpret as comparative risks. The registry record does not provide further detail about safety-event collection, attribution, or statistical comparison. These summaries should therefore be interpreted as reported counts, not as proof of a causal treatment effect.
12. What the Result Does, and Does Not, Mean
The posted record establishes that this randomized, open-label phase II study compared ipilimumab retreatment with investigator-selected chemotherapy in advanced melanoma after prior disease control with ipilimumab. Its primary outcome was overall survival from randomization to death or last known alive date. The arm-level median and range values are useful descriptive information about the results entered in the registry.
Those values do not provide a complete estimate of the treatment contrast. The registry does not report a sponsor hazard ratio, confidence interval, or p-value, and it indicates that the two-arm comparison was not estimable from the available median-time outcome values. The medians should not be interpreted as proof of benefit or lack of benefit. They also cannot show how precisely any difference is estimated, because uncertainty intervals for the medians and a comparative estimate are not reported.
The posted outcome counts are 18 for ipilimumab and 5 for chemotherapy, while the registry reports enrollment of 31. The record does not explain this difference. The reason for termination is also not reported. Numerical results for the listed secondary outcomes are not reported in the registry record, and the safety summaries use at-risk counts that differ between outcome types.
Accordingly, the registry supports a cautious account of the study design, the reported arm summaries, and the gaps in comparative and follow-up information. It does not support a definitive claim about which treatment produced better overall survival or about the magnitude or precision of a treatment effect. This interpretation concerns what the registry record reports; it is not medical advice.
13. Why This Trial Matters Statistically
This trial illustrates the difference between reporting arm-level outcome summaries and reporting a comparative treatment effect. The registry provides a median and full range for overall survival in each group, but does not provide a sponsor hazard ratio or another estimable contrast. A randomized design is intended to support comparison, yet the design alone does not supply the missing estimate or its uncertainty.
It also highlights why the type of endpoint matters. Overall survival is a time-to-event outcome, and participants may be censored at their last known alive date if no death is recorded. Medians and ranges condense the observed information, but they do not convey the full timing of events or the uncertainty of the comparison. Without a comparative estimate and precision measure, the descriptive values have limited inferential reach.
The record also makes transparent reporting important. Enrollment is listed as 31, whereas the primary outcome groups list 18 and 5. The safety groups use at-risk counts of 18 and 4. The record does not explain these differences. Nor does it give the reason for termination, secondary-outcome results, a protocol sample-size justification, or details of the statistical plan. These omissions matter because they constrain evaluation of the analysis population, completeness, and prespecification.
Finally, the trial’s sample-size assumptions are described as planning illustrations rather than the original trial design justification. Such illustrations cannot be used as observed power. Together, these features show why statistical interpretation depends not only on the reported point summaries, but also on comparison estimates, uncertainty, denominators, and transparent reporting of analysis decisions.
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 principal limitation is that the registry record does not report an estimable sponsor-reported comparison for the primary time-to-event outcome. There is no reported hazard ratio, confidence interval, or p-value for overall survival. The arm-specific medians and full ranges are descriptive and do not substitute for a comparative analysis that accounts for event timing and censoring.
The posted primary-outcome group counts are 18 and 5, while enrollment is 31. The record does not explain the difference. Safety at-risk counts are 18 and 4, including a chemotherapy denominator that differs from the primary-outcome count. These discrepancies make it difficult to understand the analysis populations and the relationship between outcome and safety reporting.
Confidence intervals for the medians, participant-level event times, numbers of deaths, and detailed censoring information are not reported in the registry record. Numerical results for Disease Control Rate and Best Overall Response Rate are also not reported. The status is terminated, but the reason for termination is not reported. The record does not report the protocol's sample-size justification, planned analysis details, multiplicity approach, or interim analyses.
The study is open-label, and chemotherapy was selected by the investigator; the record does not provide additional detail about chemotherapy regimens or the conduct of outcome assessment. These features should be kept in mind when interpreting the posted summaries. They do not establish that bias occurred, but the available record does not permit fuller assessment of these potential sources of uncertainty.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Compare the Effect of Ipilimumab Retreatment With That of Chemotherapy in Advanced Melanoma — NCT01709162.
- Registry record last updated 2015-11-30; status last verified 2015-09.
- Results first posted 2015-11-30.
- 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 describes NCT01709162, a randomized, open-label, parallel-group phase II study of ipilimumab retreatment versus investigator-selected chemotherapy for advanced melanoma after initial disease control with ipilimumab. Enrollment is listed as 31; the study status is terminated. The recorded start is 2013-03 and primary completion is 2014-07.
The primary outcome is overall survival from randomization to death or last known alive date, assessed up to 15.6 months. Posted medians are 6.3 months for ipilimumab, 3 mg/kg, and 3.1 months for chemotherapy. The registry does not report an estimable sponsor comparison. It lists Disease Control Rate and Best Overall Response Rate as secondary outcomes, without numerical results in the registry record. The reason for termination and the explanation for differing outcome and safety denominators are not reported.