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 Phase I Study of Intralesional Bacillus Calmette-Guerin (BCG) Followed by Ipilimumab in Advanced Metastatic Melanoma (NCT01838200), a non-randomized phase 1 study. The primary outcome is Number of Patients With Treatment-emergent Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01838200 |
| Phase | Phase 1 |
| Condition | Metastatic Melanoma |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ludwig Institute for Cancer Research |
| Results posted | Yes |
2. Clinical Question
The study asked whether a sequence of intralesional Bacillus Calmette-Guérin (BCG), oral isoniazid, and intravenous ipilimumab could be administered safely to patients with advanced metastatic melanoma. Its primary objective was to assess safety; the secondary objectives concerned clinical tumor response and immune-related tumor response. The registry record does not report results for those response outcomes.
Population
Patients with histologically confirmed Stage III or IV melanoma and at least 3 metastatic cutaneous or subcutaneous lesions suitable for injection, biopsy, and response evaluation. The safety analysis set was defined as patients who received at least 1 dose of study treatment.
Intervention
Intralesional BCG followed by oral isoniazid and intravenous ipilimumab. The registry describes BCG dose cohorts and a schedule in which isoniazid began 28 days after BCG and ipilimumab began 5 weeks after BCG.
Comparator
There was no randomized control group. The study was non-randomized and open-label, with groups defined by BCG dose and baseline PPD reactivity rather than a like-for-like control comparison.
Primary question
How many patients experienced treatment-emergent adverse events during the study period, which lasted continuously for up to 5 months? The registry record does not report the primary endpoint results.
The study enrolled 5 participants. It was a single-center, dose-escalation Phase I study, so its stated purpose was early evaluation of safety rather than a randomized comparison of treatment effects. The registry record does not report a treatment-effect estimate, an analysis comparing groups, or a rationale for the planned enrollment. The interpretation is therefore limited to the study objectives, design, and the adverse-event counts posted for two groups.
3. Trial Design
This was a Phase I, open-label, non-randomized, parallel-group study at a single center. The registry lists an enrollment of 5 and a terminated status. The start date was 2014-03, and the primary completion date was 2015-08-17. The reason for termination is not reported in the registry record.
Eligible participants had histologically confirmed Stage III or IV melanoma and at least 3 metastatic cutaneous or subcutaneous lesions accessible for the study procedures. The lesions were intended to permit intralesional injection, biopsy, and response evaluation. The study had a dose-escalation structure for BCG, with groups also distinguished by baseline PPD reactivity. These group assignments do not create randomized treatment comparisons.
The listed regimen began with intralesional BCG on Day 1. In the group descriptions, oral isoniazid began 28 days after BCG and continued daily for 4 weeks; intravenous ipilimumab began 5 weeks after BCG and was administered every 3 weeks. Some group descriptions are incomplete in the registry record, so additional regimen details are not reported there.
The primary objective was safety. The secondary objectives were clinical tumor response and immune-related tumor response. The primary endpoint counted participants with treatment-emergent adverse events, with the safety analysis set defined as those who received at least 1 dose of study treatment. The registry lists 3 outcome measures but no analyses. It does not report the statistical analysis plan, a sample-size justification, interim analyses, or a reason for stopping the study.
Because allocation was non-randomized and there was no control arm, differences between groups cannot be interpreted as unbiased comparative treatment effects. The small enrollment also means that the posted counts describe only a limited number of participants. The study design and registry reporting do not support conclusions about comparative efficacy.
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: The study was terminated early due to slow enrollment; thus, Cohort 1 Group 3 and Cohort 2 were not enrolled.
Overall Study
| Stage | Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) | Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) |
|---|---|---|
| STARTED | 3 | 2 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 3 | 2 |
Reasons for not completing this period:
| Reason | Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) | Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) |
|---|---|---|
| Adverse Event | 0 | 2 |
| Progressive disease | 3 | 0 |
Analysis population for the primary outcome, as defined in the registry: The Safety Analysis Set includes all patients who received at least 1 dose of study treatment.
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 Enrolled Patients
| Characteristic | Unit | Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) | Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) | Total |
|---|---|---|---|---|
| Participants analysed | 3 | 2 | 5 | |
| Age, Continuous | years | 61.3 (50 to 70) | 53.5 (43 to 64) | 58.2 (43 to 70) |
| Sex: Female, Male: Female | Participants | 1 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 2 | 1 | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 3 | 2 | 5 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 3 | 2 | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: Australia | Participants | 3 | 2 | 5 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline: 0 | Participants | 2 | 0 | 2 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) at Baseline: 1 | Participants | 1 | 2 | 3 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Patients With Treatment-emergent Adverse Events, measured over Continuously for up to 5 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the number of patients with treatment-emergent adverse events, measured continuously for up to 5 months. A treatment-emergent event was assessed from pretreatment through the study period using clinical laboratory tests, physical examinations, and vital signs. Toxicity grading followed the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
This kind of endpoint is used in an early-phase study to describe the safety experience during exposure to the investigational regimen. A participant count communicates how many people had an event; it does not, by itself, describe the event’s severity, duration, timing, or relationship to each treatment. Those details require separate reporting.
The registry also defined dose-limiting toxicity separately for BCG and ipilimumab. For BCG, it was a Grade 3 or higher local injection-site reaction involving ulceration or necrosis requiring operative intervention. For ipilimumab, it included toxicity requiring dosing modifications under local product labelling, or Grade 3 or higher hematologic or nonhematologic toxicity considered definitely, probably, or possibly related to ipilimumab.
The registry record does not report the primary endpoint count or dose-limiting toxicity results. It therefore documents how safety was to be assessed, but does not provide the results needed to describe the overall treatment-emergent adverse-event burden.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes an early-phase, non-randomized study with an enrollment of 5. Its primary purpose was to assess safety after intralesional BCG followed by isoniazid and ipilimumab. The record does not report the primary endpoint results, clinical tumor response results, or immune-related tumor response results. Consequently, the posted information does not establish the frequency of treatment-emergent adverse events across the study or provide an estimate of tumor response.
Adverse-event counts are available for two listed groups. In Cohort 1, Group 1, 3 participants were at risk for serious adverse events and 2 were affected; 3 were at risk for other adverse events and all 3 were affected. In Cohort 1, Group 2, 2 participants were at risk for serious adverse events and 1 was affected; 2 were at risk for other adverse events and both were affected. No deaths are listed in either group. These are small group counts, and they should be read as descriptions of the recorded participants rather than stable estimates of event frequency.
The registry lists colitis at 50.0%, pleural effusion at 33.3%, and lymph node pain at 33.3% among the top serious adverse-event terms. The denominator and counting rules for these percentages are not reported in the registry record. The percentages therefore cannot be used to infer how many participants had each term or whether events occurred in one or both groups.
There is no randomized control group, and the groups were not allocated as a like-for-like comparison. Their BCG dose levels and baseline PPD reactivity criteria differ. Any apparent difference in counts could reflect the group definitions, the small numbers, or other differences rather than a treatment effect. The registry record does not report an adjusted or unadjusted comparison.
These limitations are important for interpreting both safety and response. A small study can identify observations that merit description, but sparse counts do not precisely characterize uncommon events. Likewise, the stated response objectives are not accompanied by posted results or analyses. The appropriate reading is therefore that the registry records selected safety counts and a study plan, not a conclusive estimate of safety or efficacy.
9. Statistical Methods Explained
The registry record gives the study’s design and outcome definitions but does not report inferential analyses. No statistical analysis plan, hypothesis tests, confidence intervals, or treatment-effect estimates are reported in the registry record. Statistical concepts can still help explain what these design features permit and what they leave uncertain.
What does a participant count describe?
A count reports the number of participants meeting an endpoint definition. For adverse events, a count should be interpreted alongside the number of participants who could have experienced the event and the precise event definition. In a small study, each participant accounts for a substantial part of the observed count, so the count can change noticeably with the experience of a single participant. A count alone does not show how precisely the underlying event frequency has been estimated.
The primary endpoint was a count of participants with treatment-emergent adverse events. The registry defines the safety analysis set as all patients who received at least 1 dose of study treatment. The posted results do not give the primary endpoint count, so its overall frequency cannot be described from the registry record. Group-level serious and other adverse-event counts are separate safety information and should not be substituted for the unreported primary endpoint.
Why does non-randomized allocation matter?
Random allocation is a method for making groups comparable, on average, with respect to both measured and unmeasured characteristics. This study was non-randomized. Its group descriptions distinguish BCG dose levels and baseline PPD reactivity, so group membership was tied to those criteria rather than assigned randomly. A difference in observed outcomes between groups would therefore not isolate the effect of BCG dose or another component of the regimen. The registry itself notes that the arms are not a like-for-like control comparison.
Open-label conduct means the study was not masked. The registry does not report blinding procedures. When outcomes involve clinical assessment or event reporting, knowledge of treatment can sometimes affect ascertainment or classification; this is a general methodological concern, not evidence that such bias occurred in this study. The registry’s descriptions of laboratory tests, physical examinations, vital signs, and toxicity grading help specify how safety was assessed, but do not establish whether assessment was blinded.
What does a confidence interval add?
In general, a confidence interval describes uncertainty around an estimated quantity under the assumptions of the analysis. It can show whether the data are compatible with a range of values, rather than presenting a single estimate alone. No confidence intervals are reported in the registry record. With small participant counts, an estimate would generally be uncertain; without reported estimates and intervals, the precision of the study’s safety findings cannot be assessed quantitatively.
Why can over-dispersion matter?
In general, over-dispersion occurs when observed variation is greater than a statistical model assumes. It matters when a model relies on a particular relationship between the average outcome and its variability, because understated variability can lead to overly narrow uncertainty intervals or misleading tests. The registry record does not report a model for count data, repeated measures, or an assessment of over-dispersion. There is no basis for saying that this issue was assessed or that a particular model was used.
What can be inferred from the safety figures?
The group counts describe the participants recorded as at risk and affected for serious and other adverse events. They are not a randomized comparison, and the registry does not report statistical tests of group differences. The percentages for the listed serious adverse-event terms also lack a reported denominator and counting method. General statistical practice would require clear definitions of the analysis unit, follow-up, and denominator before interpreting such percentages as participant-level risks.
The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning illustrations, not observed power. The registry does not report that these assumptions were used to design this Phase I study, and it does not report a sample-size justification. Because the study was non-randomized, a planning comparison between two arms would not convert its groups into a valid randomized comparison.
Overall, the design and outcome definitions can be described, but statistical inference is constrained by the absence of reported analyses and primary endpoint results. Any numerical interpretation should remain descriptive and tied to the specific group counts and definitions recorded.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures: the primary safety measure and secondary measures for best overall clinical tumor response and best overall immune-related tumor response. It reports no analyses. A statistical analysis plan, including any prespecified hierarchy or adjustment for multiple outcomes, is not reported in the registry record.
Multiplicity arises when several outcomes, groups, or analyses are examined. In general, the more comparisons considered, the greater the chance of obtaining an apparently notable result by chance if each is assessed separately. A prespecified strategy can clarify which outcome is primary and how secondary findings should be interpreted. The registry identifies the safety endpoint as primary and the response objectives as secondary, but does not report how analyses across those outcomes were planned or handled.
Missing-data procedures are not reported in the registry record. The record defines the safety analysis set as participants who received at least 1 dose of study treatment, but it does not describe the analysis population for tumor response, how missing assessments were handled, or whether any participants lacked outcome data. It also does not report follow-up completeness or reasons for missing observations.
The distinction matters because exclusion, imputation, or other handling of incomplete observations can affect the interpretation of outcomes. No particular approach should be assumed. The registry’s definition of the safety population is the only stated analysis-population detail for the primary endpoint.
Finally, no interim analyses, stopping rules, or statistical analysis plan are reported in the registry record. The study status is terminated, but the reason for termination is not reported. Without these details, it is not possible to determine whether the termination related to safety, recruitment, operational considerations, or another reason.
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 |
|---|---|---|---|
| Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) | 2 | 3 | 66.7% |
| Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) | 1 | 2 | 50.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) | 0 of 3 |
| Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) | 0 of 2 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) | 3 of 3 |
| Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) | 2 of 2 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) | Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) |
|---|---|---|---|
| Colitis | Gastrointestinal disorders | 0 of 3 | 1 of 2 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 1 of 3 | 0 of 2 |
| Lymph node pain | Blood and lymphatic system disorders | 1 of 3 | 0 of 2 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1, Group 1 (BCG 0.16-0.64 × 10^6 CFU) | Cohort 1, Group 2 (BCG 0.8-3.2 × 10^6 CFU) |
|---|---|---|---|
| Fatigue | General disorders | 2 of 3 | 2 of 2 |
| Constipation | Gastrointestinal disorders | 2 of 3 | 1 of 2 |
| Nausea | Gastrointestinal disorders | 2 of 3 | 1 of 2 |
| Pruritus | Skin and subcutaneous tissue disorders | 1 of 3 | 2 of 2 |
| Axillary pain | General disorders | 2 of 3 | 0 of 2 |
| Back pain | Musculoskeletal and connective tissue disorders | 2 of 3 | 0 of 2 |
| Decreased appetite | Metabolism and nutrition disorders | 1 of 3 | 1 of 2 |
| Insomnia | Psychiatric disorders | 1 of 3 | 1 of 2 |
| Night sweats | Skin and subcutaneous tissue disorders | 2 of 3 | 0 of 2 |
| Abdominal pain | Gastrointestinal disorders | 0 of 3 | 1 of 2 |
Serious events with the highest arm-level rate: colitis (50.0%), pleural effusion (33.3%), lymph node pain (33.3%).
The registry posts serious and other adverse-event counts for two groups. In Cohort 1, Group 1, the serious-event count was 2 affected among 3 at risk, and the other-event count was 3 affected among 3 at risk. In Cohort 1, Group 2, the serious-event count was 1 affected among 2 at risk, and the other-event count was 2 affected among 2 at risk. No deaths are listed in either group.
These figures are counts from small groups, not precise estimates of event risk. The groups were non-randomized and differed in their BCG dose descriptions; they should not be treated as control and treatment arms in a comparative trial. The registry lists colitis at 50.0%, pleural effusion at 33.3%, and lymph node pain at 33.3% among the top serious adverse-event terms. The denominator and method used for these percentages are not reported in the registry record, so they cannot be translated into participant counts from the posted information alone.
The primary endpoint was the number of patients with treatment-emergent adverse events, but its result is not reported in the registry record. The group-level counts do not replace that missing overall result, and they do not indicate the severity, timing, duration, or treatment attribution of each event.
12. What the Result Does, and Does Not, Mean
The record documents a Phase I study intended to evaluate safety and explore clinical and immune-related tumor responses for a regimen of intralesional BCG followed by isoniazid and ipilimumab. It gives eligibility criteria, treatment schedules, safety definitions, and selected adverse-event counts for two groups. It does not report the primary endpoint result or the secondary response results.
The serious and other adverse-event figures are descriptive counts in a small, non-randomized study. They show that adverse events were recorded among participants in the listed groups, but they do not provide a precise estimate of how often events would occur in a broader population. The top serious-event terms are reported as percentages, but their denominator and counting method are not stated. No deaths are listed for the two groups described.
These data do not establish whether the regimen is safe or unsafe overall. That judgment would require a complete account of event types, severity, timing, attribution, exposure, follow-up, and the primary safety outcome. Nor do the data establish whether the regimen changed tumor response. The response objectives are named, but corresponding results and analyses are not reported in the registry record.
Because allocation was non-randomized and the groups were not designed as like-for-like controls, their counts cannot be used to estimate comparative treatment effects. The record also does not explain why the study was terminated. The most defensible conclusion is limited: the registry describes an early-phase study and posts selected safety counts, while leaving the main outcome results and the reason for termination unreported.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the distinction between a study’s objectives and the results needed to answer them. The registry identifies safety as the primary objective and tumor response and immune response as secondary objectives. Yet it reports no analyses and no result for the primary safety measure. A clearly stated endpoint is important, but an endpoint definition alone is not evidence about the outcome.
The study also illustrates why design determines what comparisons can mean. A non-randomized, dose-escalation study can describe the experience of participants in its groups, but differences between those groups do not provide the same interpretation as a randomized comparison. Here, group definitions include BCG dose and baseline PPD reactivity, and the record explicitly notes that the arms are not a like-for-like control comparison.
Small participant counts make transparent reporting especially important. Counts, denominators, event definitions, and follow-up context are needed to judge what the observations represent. The record gives group-level serious and other event counts, while leaving the overall primary endpoint result and the denominator for the listed serious-event percentages unreported. This limits both descriptive interpretation and any assessment of precision.
Finally, the terminated status without a reported reason shows why status alone does not explain a study’s course. The record does not say whether termination was related to safety, recruitment, or another consideration. Taken together, the study highlights the value of complete outcome reporting and careful separation of descriptive safety observations from comparative conclusions.
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 enrollment was 5, and the record reports safety counts for only two groups. This limits how broadly the observed counts can characterize adverse events. The primary treatment-emergent adverse-event result is not reported in the registry record, even though safety was the primary objective. The secondary clinical and immune-related response results are also not reported.
The study was non-randomized and open-label, with no control group. Group membership reflected BCG dose and baseline PPD reactivity criteria. Consequently, group differences cannot be attributed to a treatment component on the basis of this record. The registry itself cautions that the arms are not a like-for-like control comparison.
Some regimen descriptions in the registry are incomplete. While the listed schedule includes intralesional BCG on Day 1, isoniazid beginning 28 days later for 4 weeks, and ipilimumab beginning 5 weeks later every 3 weeks, further details for some groups are not reported in the registry record. The reason for termination is also not reported.
The record does not report a statistical analysis plan, sample-size justification, interim analyses, missing-data procedures, confidence intervals, or statistical tests. The denominator and counting method for the top serious adverse-event percentages are not reported. These gaps prevent assessment of precision, completeness, and the intended analytical handling of outcomes. The available information supports a limited descriptive account, not a conclusive estimate of safety or treatment effect.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase I Study of Intralesional Bacillus Calmette-Guerin (BCG) Followed by Ipilimumab in Advanced Metastatic Melanoma — NCT01838200.
- Registry record last updated 2022-10-12; status last verified 2022-10.
- Results first posted 2019-03-28.
- 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
NCT01838200 was a single-center, open-label, non-randomized Phase I study of intralesional BCG followed by oral isoniazid and intravenous ipilimumab in advanced metastatic melanoma. The registry lists an enrollment of 5, a terminated status, and a primary completion date of 2015-08-17. The reason for termination is not reported in the registry record.
The primary objective was safety; clinical and immune-related tumor responses were secondary objectives. The record defines the safety endpoint and analysis set and posts serious and other adverse-event counts for two groups. It does not report the primary endpoint result, response results, statistical analyses, or the statistical analysis plan. The non-randomized groups do not support a like-for-like treatment comparison.