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 Doxycycline, Temozolomide and Ipilimumab in Melanoma (NCT01590082), a na phase 1, phase 2 study. The primary outcome is Overall Participant Response.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01590082 |
| Phase | Phase 1, Phase 2 |
| Condition | Melanoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 12 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Participants with metastatic melanoma were eligible for a study intended to examine the combination. The registry record lists melanoma as the condition and reports enrollment of 12. It does not provide enough information to characterize the participants further, such as their baseline disease status or other eligibility details.
Intervention
The study combined doxycycline, temozolomide, and ipilimumab. Its stated aim included finding the highest tolerable doxycycline dose for use with the other drugs, alongside studying safety and effectiveness. The registry record describes a dosing sequence for the Phase I group, but the available arm description ends before the complete regimen is given.
Comparator
No concurrent control group is listed. The registry record identifies the model as single-group and allocation as NA, so it does not describe a randomized comparison. The Phase II group listed in the safety record is not a like-for-like control group.
Primary question
The listed primary outcome is the number of participants with a response under RECIST version 1.1, assessed over 2 cycles, up to 7 weeks. The registry record says that early termination meant participants did not move to Phase 2 and no data were collected for this outcome. As a result, the listed endpoint does not establish how many participants responded.
3. Trial Design
The registry record describes a Phase I / II, single-group study sponsored by M.D. Anderson Cancer Center. It lists doxycycline, ipilimumab, and temozolomide as the interventions and metastatic melanoma as the study context. Enrollment is recorded as 12. The study started in 2012-11, had primary completion in 2015-07, and is marked terminated.
The stated Phase I aim was to find the highest tolerable dose of doxycycline that could be combined with temozolomide and ipilimumab. The study also set out to examine safety and effectiveness. This is a dose-finding and early evaluation objective, rather than a randomized test against a concurrent control. The record lists allocation as NA, masking as none, and the model as single-group. It does not describe a parallel control treatment.
The listed Phase I regimen began doxycycline on day -6 of Cycle 1, followed by ipilimumab on Day 1 and temozolomide that evening. The description says temozolomide was taken once a day for 4 days, but the remainder of the arm description is truncated. A complete account of dosing, dose escalation, or treatment modifications is not reported in the registry record.
The primary outcome was overall participant response by RECIST version 1.1. However, the record states that early termination prevented participants from moving to Phase 2 and that no data were collected for the primary outcome. A Phase II group nevertheless appears in the safety record, with 1 participant at risk. The record does not explain this entry or reconcile it with the statement about Phase 2 progression. These details should be read as separate registry entries, not as evidence of a completed Phase II efficacy assessment.
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 | Phase I: Doxycycline + Ipilimumab + Temozolomide | Phase II |
|---|---|---|
| STARTED | 11 | 1 |
| COMPLETED | 9 | 1 |
| NOT COMPLETED | 2 | 0 |
Reasons for not completing this period:
| Reason | Phase I: Doxycycline + Ipilimumab + Temozolomide | Phase II |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
| Ineligible | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Due to early termination participants did not move to Phase 2 and no data collected.
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 | Phase I: Doxycycline + Ipilimumab + Temozolomide | Phase II | Total |
|---|---|---|---|---|
| Participants analysed | 11 | 1 | 12 | |
| Age, Continuous | years | 66 (53 to 75) | 84 (84 to 84) | 67 (53 to 84) |
| Sex: Female, Male: Female | Participants | 3 | 0 | 3 |
| Sex: Female, Male: Male | Participants | 8 | 1 | 9 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 11 | 0 | 11 |
| 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 | 11 | 1 | 12 |
| 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: United States | participants | 11 | 1 | 12 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Participant Response, measured over 2 cycles, up to 7 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The listed primary endpoint is the number of participants with a response according to RECIST version 1.1 over 2 cycles, up to 7 weeks. RECIST classifies changes in target lesions using measurements over time. The recorded definitions include complete response, partial response, stable disease, progressive disease, not applicable, and not evaluable. The criteria specify disappearance of target lesions for complete response; a decrease of >30% in the sum of target-lesion diameters for partial response; and an increase of >20%, with an absolute increase from nadir of 5mm, for progressive disease. The description also defines pathological lymph nodes using a short-axis threshold of <10mm.
General explanation: a response endpoint converts lesion measurements into categories that can be counted across participants. This can provide a consistent way to describe tumor change within a specified assessment period. The categories are not interchangeable: stable disease, for example, is distinct from a partial response, and an unevaluable assessment is not itself evidence of response or progression.
The registry record reports no response count and says no primary-outcome data were collected because of early termination. Therefore, the endpoint is defined, but its result is unavailable. The record does not report the assessment procedures, adjudication process, or analysis population beyond the endpoint description.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clinically relevant statistical question—whether participants had a RECIST-defined response during the stated assessment period—but does not provide the response observations needed to answer it. Although enrollment is recorded as 12, the primary-outcome description explicitly says that no data were collected after early termination and that participants did not move to Phase 2. Enrollment alone cannot be treated as the number assessed for response, nor can it be used to infer a response rate.
No primary outcome estimate, uncertainty interval, hypothesis test, or analysis is listed. The record reports 0 participants with serious adverse events in each of the safety groups shown, while the separate other-adverse-event counts are 9 and 1. These safety counts do not supply evidence about the missing RECIST outcome. They also do not show that every enrolled participant had a complete safety follow-up; the record does not provide follow-up completeness or explain the safety denominators.
There is no randomized comparator. A single-group study can describe observations among participants who received the study combination, but without a concurrent control it cannot separate treatment-associated changes from other explanations, including the natural course of disease or differences in assessment and follow-up. In this record, even a descriptive response estimate is unavailable because response data are stated not to have been collected.
General explanation: an estimate describes the observed data, while an uncertainty interval communicates how imprecise that estimate may be under a statistical model. Neither can be interpreted when the relevant outcome observations and analysis are absent. A p-value would address a specified statistical comparison or hypothesis; no such result is reported. It would be inappropriate to infer efficacy, lack of efficacy, or a treatment effect from the fact that the trial terminated.
The safety entries should also be interpreted narrowly. A recorded count of 0 serious adverse events means no participants in that listed group were counted as affected in that registry field; it does not by itself establish absence of risk. The record does not list serious-event terms, and deaths are not numerically reported. The separate other-event counts are not substitutes for a full account of event type, timing, severity, or duration.
Overall, the posted record documents study intent, design features, termination, and limited safety counts. It does not provide an efficacy result or the statistical analysis needed to quantify how precisely any effect was estimated.
9. Statistical Methods Explained
The registry record identifies the study as Phase I / II, single-group, and unmasked, with allocation listed as NA. It lists one primary outcome and no analyses. It does not report a statistical analysis plan, a sample-size justification, or a completed analysis of the response endpoint. The methods below explain general statistical ideas relevant to interpreting such a record; they are not claims about methods that the investigators used.
What does a single-group design allow?
General explanation: a single-group study can describe what happened among participants receiving the study combination. It can be useful for documenting tolerability and exploring whether outcomes merit further study. Without a concurrent comparison group, however, changes cannot be attributed uniquely to the treatment combination. Factors such as the course of disease, selection of participants, other care, and the timing of outcome assessment can also affect observed outcomes. The registry does not describe a randomized allocation or a control treatment.
What does the Phase I aim imply?
General explanation: dose-finding studies commonly focus on identifying a dose that can be given within specified tolerability criteria. That aim is distinct from estimating a comparative treatment effect. To interpret a dose-finding result, readers would need details such as the planned dose levels, rules for dose escalation, criteria for dose-limiting toxicity, and the decision rule for selecting a dose. Those details are not reported in the registry record. The study’s stated goal does not establish that a highest tolerable dose was identified.
How should the response endpoint be understood?
The endpoint uses RECIST version 1.1 categories and counts participants with response. General explanation: turning lesion measurements into predefined categories can support consistent outcome classification, but a count requires observed assessments and an analysis population. The record says no primary-outcome data were collected because of early termination. Thus there is no observed response count to interpret, and no basis for calculating a response proportion or its uncertainty.
General explanation: when an outcome is a count of participants with an event, analysts may model the count or the corresponding probability, depending on the design and analysis plan. The choice of model, handling of incomplete assessments, and uncertainty calculation should be prespecified or transparently documented. No model, interval estimate, or hypothesis test for the primary outcome is reported.
Why do uncertainty and analysis plans matter?
General explanation: an estimate alone does not show how much uncertainty surrounds it. A confidence interval is a range generated by a statistical procedure that, under its assumptions, conveys the precision of an estimate. The interval’s interpretation depends on the data, the analysis method, and the assumptions. No confidence interval is listed for the primary endpoint. Because the endpoint observations are absent, an interval cannot be reconstructed from the registry information.
A statistical analysis plan also specifies which participants contribute to each analysis, how outcomes are defined, and how missing or unevaluable assessments are handled. These choices can affect interpretation. The registry record does not report these details. It also does not report interim analyses, stopping rules, or whether any analyses were planned at the time of early termination. Their absence from the record should not be taken as proof that no such procedures existed; their status is not reported in the registry record.
What can the safety counts support?
General explanation: adverse-event counts are descriptive unless accompanied by a defined comparison and analysis. The serious-event fields report participants at risk and participants affected, while other adverse events are shown separately. Counts do not describe event duration, severity grading, recurrence, or causal attribution unless those details are reported. The registry record lists no serious-event terms, and it does not provide an inferential safety analysis. Counts should therefore be read as registry summaries, not as comprehensive estimates of comparative safety.
The sample-size assumptions recorded for planning illustrations describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. These are illustration assumptions, not evidence of the trial’s own design or a completed power analysis. The registry record does not report a trial-specific sample-size justification, and there is no observed primary effect from which to draw conclusions about power. Any planning illustration should be understood as hypothetical rather than as observed power or a result of this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists overall participant response as the primary outcome and reports one outcome measure. It lists no analyses. A statistical plan for managing multiple outcomes, comparisons, or repeated assessments is not reported in the registry record. There is therefore no basis for saying whether multiplicity adjustments were planned or used.
General explanation: when several hypotheses are tested, the chance of obtaining at least one apparently notable result can increase if each test is interpreted independently. A prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory analyses can help readers interpret multiple results. These are general options, not methods documented for this study. The absence of reported analyses means no multiplicity-adjusted or unadjusted result can be evaluated.
The record states that no primary-outcome data were collected because the study terminated early and participants did not move to Phase 2. It does not provide a participant flow, reasons for individual discontinuation, missing assessment counts, or rules for classifying unevaluable outcomes. A missing response assessment cannot be assumed to indicate response, nonresponse, or disease progression. The registry record does not report an imputation method or a sensitivity analysis for missing outcomes.
Analysis populations are also not described. The record does not say which participants would have been included in an efficacy analysis, how protocol deviations would be handled, or how the safety populations were defined. The safety entries list 9 participants at risk in the Phase I group and 1 in the Phase II group, but the record does not explain how these counts relate to enrollment of 12. These figures should not be reconciled by assumption. The registry record also does not report interim analyses or the statistical procedures, if any, associated with early termination.
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 |
|---|---|---|---|
| Phase I: Doxycycline + Ipilimumab + Temozolomide | 0 | 9 | 0.0% |
| Phase II | 0 | 1 | 0.0% |
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 |
|---|---|
| Phase I: Doxycycline + Ipilimumab + Temozolomide | 9 of 9 |
| Phase II | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase I: Doxycycline + Ipilimumab + Temozolomide | Phase II |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 9 of 9 | 1 of 1 |
| Anorexia | Metabolism and nutrition disorders | 7 of 9 | 1 of 1 |
| Fatigue | General disorders | 7 of 9 | 1 of 1 |
| Pruritus | Skin and subcutaneous tissue disorders | 6 of 9 | 1 of 1 |
| Aspartate aminotransferase increased | Investigations | 5 of 9 | 1 of 1 |
| Edema limbs | Musculoskeletal and connective tissue disorders | 6 of 9 | 0 of 1 |
| Headache | Nervous system disorders | 6 of 9 | 0 of 1 |
| Anemia | Blood and lymphatic system disorders | 5 of 9 | 0 of 1 |
| Dizziness | Nervous system disorders | 5 of 9 | 0 of 1 |
| Dry skin | Skin and subcutaneous tissue disorders | 5 of 9 | 0 of 1 |
The safety record separates serious adverse events from other adverse events. For the Phase I combination group, 9 participants are listed at risk for serious events and 0 as affected; 9 are listed at risk for other adverse events and 9 as affected. For the Phase II group, 1 participant is listed at risk for serious events and 0 as affected; 1 is listed at risk for other adverse events and 1 as affected. No top serious-event terms are listed.
These are registry counts, not a complete narrative of safety. The record does not report event types for the other adverse events, their severity, timing, duration, recurrence, or investigators’ attribution. The entries also do not establish that every participant had the same length of follow-up. The deaths field is null, so deaths are not reported in the registry record; a null value should not be read as a count of zero.
General explanation: a count of participants affected is different from a count of events, because one participant may experience more than one event. The record gives participant counts in the displayed fields and should not be interpreted as an event total. Nor do these single-group counts establish comparative safety. The record does not explain why a Phase II safety group is listed despite stating that participants did not move to Phase 2.
12. What the Result Does, and Does Not, Mean
The registry record supports a limited description of study conduct and posted outcomes. It describes a single-group Phase I / II combination study, states that its aim included dose finding and safety and effectiveness assessment, and records early termination. It defines a RECIST response endpoint but explicitly says no data were collected for that endpoint. The record therefore does not report an efficacy result.
The safety fields report 0 participants affected by serious adverse events in the listed Phase I and Phase II groups, alongside other-adverse-event counts of 9 and 1. These figures describe the registry entries; they do not provide a complete safety profile or a comparison with another treatment. The record does not report deaths as a numeric value, serious-event terms, or a detailed account of other events.
General explanation: a study’s intent is not the same as its result. Naming a response endpoint does not mean that response was measured or observed. Likewise, early termination does not itself show that a treatment was ineffective, unsafe, or beneficial. It means the intended evidence may not have been collected or reported, and the reason for termination is not reported in the registry record.
Because there is no concurrent control group, even a reported response count would have described outcomes in this group rather than established a causal treatment effect. In this record, the response count itself is unavailable. No estimate, confidence interval, or statistical test is posted for the primary outcome. Neither a positive nor a negative efficacy conclusion can be drawn from the missing outcome data.
The study record is therefore informative about the planned question and the limits of the available results, but it does not answer whether the combination produced RECIST responses or how precisely such an effect could be estimated. Interpretation should remain within those boundaries.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction between a clearly defined endpoint and an observed endpoint result. The registry specifies a RECIST-based response measure and an assessment period, but also records that no primary-outcome data were collected after early termination. A statistical question can be well described without being answerable from the posted results.
The design context matters as well. A single-group study can support descriptive reporting, particularly when the aim includes dose finding, but it does not offer a concurrent randomized comparison. Statistical interpretation should therefore distinguish the study’s exploratory and tolerability aims from evidence of comparative effectiveness. In this case, the missing response observations limit even the descriptive efficacy account.
The record also shows why safety denominators and event categories need careful reading. Serious and other adverse events appear in distinct fields, and the listed group counts do not explain how they relate to total enrollment. The Phase II safety entry is not resolved by the statement that participants did not move to Phase 2. Treating unclear registry entries as if they formed a complete participant flow would go beyond the record.
General explanation: transparent reporting of analysis populations, missing data, uncertainty estimates, and stopping decisions helps readers distinguish a lack of evidence from evidence of no effect. Those details are not reported in the registry record. The statistical lesson is not a conclusion about the treatment, but a reminder that endpoint definitions, observed data, and analysis results are separate parts of the evidence chain. When the latter parts are absent, interpretation must remain correspondingly limited.
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.
A central limitation is that the registry record says no primary-outcome data were collected. The listed RECIST endpoint therefore has no reported response count, estimate, or uncertainty interval. The reason for early termination is not reported in the registry record, so its implications for follow-up and data availability cannot be determined from the entry.
The single-group model and lack of a listed control treatment limit causal interpretation. Allocation is listed as NA and masking as none. The record does not describe a concurrent comparator, randomization, or blinded outcome assessment. Even if response data had been available, the design would not support a direct randomized treatment comparison.
Important methods are not reported in the registry record: a full statistical analysis plan, sample-size justification, dose-escalation rules, dose-limiting toxicity criteria, analysis populations, missing-data procedures, and interim or stopping analyses. The arm description is incomplete. The registry record also does not provide detailed baseline characteristics or a participant flow that would clarify how enrollment relates to the safety groups.
Safety reporting is limited to participant counts in serious and other adverse-event fields. Serious-event terms are not listed, and deaths are not numerically reported. Details about event types, severity, duration, attribution, and follow-up are not reported in the registry record. The relationship between the Phase II safety entry and the statement that participants did not move to Phase 2 is also unexplained.
These limitations do not establish that unreported procedures or data did not exist. They mean that the registry record does not make them available for statistical assessment. Conclusions should be restricted to the stated design, endpoint definition, termination status, and posted safety counts.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Doxycycline, Temozolomide and Ipilimumab in Melanoma — NCT01590082.
- Registry record last updated 2020-09-02; status last verified 2020-08.
- Results first posted 2020-09-02.
- 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 record describes a terminated Phase I / II, single-group study of doxycycline with temozolomide and ipilimumab in melanoma, sponsored by M.D. Anderson Cancer Center. Enrollment is listed as 12. The study started in 2012-11, with primary completion in 2015-07.
The stated aims included identifying the highest tolerable doxycycline dose for the combination and studying safety and effectiveness. Overall participant response by RECIST version 1.1 was the listed primary outcome, assessed over 2 cycles, up to 7 weeks. The record says early termination meant participants did not move to Phase 2 and no primary-outcome data were collected.
No analyses are listed. Safety entries report 0 participants with serious adverse events in each listed group, with other-adverse-event counts of 9 for Phase I and 1 for Phase II. Serious-event terms are not listed, and deaths are not reported numerically. The record does not provide a primary response result or a statistical estimate of treatment effect.