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/II Study of Irinotecan and Temsirolimus in Patients With Refractory Sarcomas (NCT00996346), a non-randomized phase 1 study. The primary outcome is Maximum Tolerated Dose (MTD) of Irinotecan.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00996346 |
| Phase | Phase 1 |
| Condition | Sarcoma |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 17 |
| Arms in the primary outcome | n/a |
| Lead sponsor | New Mexico Cancer Research Alliance |
| Results posted | Yes |
2. Clinical Question
Population
Patients with refractory soft tissue sarcoma were the intended population. The record describes sarcoma as the condition and states that the study goal concerned patients whose disease was refractory. It does not report further eligibility details or a more specific description of the enrolled population.
Intervention
The study evaluated intravenous irinotecan combined with intravenous temsirolimus, administered weekly for three consecutive doses followed by one week of rest; one cycle was four weeks. The registry lists three dose levels. The listed irinotecan doses were 80 mg/m2 for the first two levels and 50 mg/m2 for the third. The listed temsirolimus doses were 15 mg, 20 mg, and 25 mg, respectively.
Comparator
There was no randomized control group. The record classifies allocation as non-randomized and the model as single-group. The dose levels are not a like-for-like control comparison: patients were assigned to dose groups, and the record does not describe a randomized allocation process. Results across the groups should therefore not be read as a controlled estimate of a treatment difference.
Primary question
The primary question was the maximum tolerated dose of irinotecan when given with temsirolimus. The outcome definition identifies the MTD as the dose preceding a dose at which at least 2 out of 3 patients in the treatment group experience a dose-limiting toxicity. The registry record does not report a numeric MTD result.
The rationale in the record is that mTOR inhibitors such as temsirolimus had shown activity in sarcoma, and irinotecan had also been used to treat sarcoma, while the efficacy and toxicity of combining the drugs were uncertain. The stated phase I aim was to determine the MTD and toxicity profile of the combination. This is a dose-finding and safety question, not a randomized test of whether the combination is more effective than another treatment. The outcome description defines toxicities that count as dose-limiting; it does not establish that any particular toxicity occurred. Because no numeric primary result or analysis is reported in the registry record, the dose-finding question cannot be answered from the posted results alone.
3. Trial Design
The registry classifies the study as Phase I, non-randomized, unmasked, and single-group. Although the study title says Phase I/II, the phase classification in the record is Phase I. The record lists an enrollment of 17. It gives a start date of 2009-10, a primary completion date of 2011-11, and a status of terminated. These administrative details describe the registered study; the record does not state why it was terminated or what consequences termination had for data collection.
Three combination dose levels are listed. At the first level, irinotecan was 80 mg/m2 and temsirolimus was 15 mg. At the second, irinotecan was 80 mg/m2 and temsirolimus was 20 mg. At the third, irinotecan was 50 mg/m2 and temsirolimus was 25 mg. Each regimen is described as intravenous dosing on a weekly basis for three consecutive doses, followed by one week of rest, with one cycle lasting four weeks. The third intervention label says “Arm 2, Level 1,” while its description says “Arm 1, Level 2.” That labeling inconsistency is not resolved in the registry record.
The design is not a randomized comparison between treatment and control. Instead, the registry describes groups receiving different dose combinations. Such groups can provide descriptive information about dosing and toxicity, but differences between them cannot automatically be attributed to the dose: assignment was non-randomized, and the record gives no adjusted analysis. The posted risk counts are 6, 8, and 3 for the three listed dose groups. Those counts describe the adverse-event reporting groups; the record does not explain how they relate to the enrollment total or to the analysis population for the primary outcome.
The record does not report a protocol-level sample-size justification, dose-escalation algorithm, or detailed analysis plan. Nor does it report participant flow, reasons for discontinuation, or the number evaluated for the primary endpoint. These gaps limit reconstruction of how the intended dose-finding design was implemented.
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 | Irinotecan&Temsirolimus:Arm 1, Level 1 | Irinotecan&Temsirolimus:Arm 1, Level 2 | Irinotecan&Temsirolimus:Arm 2, Level 1 |
|---|---|---|---|
| STARTED | 6 | 8 | 3 |
| COMPLETED | 6 | 8 | 3 |
| NOT COMPLETED | 0 | 0 | 0 |
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 | Irinotecan&Temsirolimus:Arm 1, Level 1 | Irinotecan&Temsirolimus:Arm 1, Level 2 | Irinotecan&Temsirolimus:Arm 2, Level 1 | Total |
|---|---|---|---|---|---|
| Participants analysed | 6 | 8 | 3 | 17 | |
| Age, Continuous | years | 60.5 (48 to 69) | 47.5 (25 to 72) | 56 (56 to 64) | 56 (25 to 72) |
| Sex: Female, Male: Female | Participants | 3 | 4 | 1 | 8 |
| Sex: Female, Male: Male | Participants | 3 | 4 | 2 | 9 |
| Region of Enrollment: United States | participants | 6 | 8 | 3 | 17 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Tolerated Dose (MTD) of Irinotecan, measured over Up to 1 month.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | milligrams/meter squared |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the maximum tolerated dose of irinotecan, measured in milligrams per meter squared, with a timeframe of up to 1 month. The record defines the MTD as the dose preceding the dose at which at least 2 out of 3 patients in the treatment group experience a dose-limiting toxicity. The listed dose-limiting toxicities are grade 3 neutropenia on retreatment day, grade 4 febrile neutropenia, drug-related grade 3 or 4 non-hematologic toxicity—with exceptions for fatigue, nausea, vomiting, or grade 3 hypersensitivity reaction—or grade 2 or greater motor or sensory neuropathy.
In general, an MTD endpoint is used in early-phase dose-finding to identify a dose boundary based on a prespecified toxicity rule. It focuses on tolerability during the defined observation period rather than on comparative efficacy. The toxicity threshold gives the endpoint an operational meaning, but interpreting it also requires knowing how patients were assigned to dose levels, how DLTs were assessed, and how unevaluable participants were handled. Those details are not reported in the registry record.
The endpoint definition is present, but a numeric MTD result is not reported in the registry record. Therefore, the posted information does not identify which irinotecan dose met the MTD rule, nor does it show the number of dose-limiting events used to reach a conclusion. The endpoint should be understood as the study’s stated primary measure, not as a result established by the available registry data.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes an early-phase, non-randomized dose-finding study of irinotecan plus temsirolimus in refractory sarcomas. Its primary objective was to determine the MTD of irinotecan in the combination and to describe toxicity. That objective is distinct from estimating whether the regimen improves clinical outcomes relative to a comparator. No randomized comparator is described, and the record explicitly identifies the study as non-randomized and single-group.
The primary endpoint has a clear toxicity-based definition, but the numeric MTD result is not reported in the registry record. The record therefore does not tell readers which dose was selected, whether the DLT threshold was reached at any dose, or how many participants experienced each DLT. There are no posted analyses listed. Consequently, the primary dose-finding question cannot be answered from the record as captured, and no estimate of uncertainty around an MTD can be assessed.
For adverse events, the three groups list 0 serious events among 6, 0 among 8, and 0 among 3 participants at risk. The record lists no serious adverse-event terms. It also lists other adverse events affecting 6 of 6, 8 of 8, and 3 of 3 participants in those respective groups. These are descriptive counts. The record does not provide event-level detail for the other adverse events in this summary, severity distributions, exposure-adjusted rates, or an explanation of missingness. Death counts are null, which means deaths are not reported in the registry record; null should not be read as zero deaths.
Even if dose-group outcomes were available, the groups would not constitute a randomized comparison. The group sizes are small and unequal, and the combination doses vary in more than one way across the listed levels. Without an allocation method, baseline characteristics, participant-level outcomes, and a prespecified analysis, apparent differences could reflect participant composition or other factors as well as dose. The registry record does not report adjusted comparisons or confidence intervals.
General statistical interpretation: a confidence interval describes a range of values reasonably compatible with an estimate under the analysis assumptions. Its width communicates precision, while the estimate alone does not. No confidence interval for the MTD or other primary-outcome estimate is reported in the registry record, so precision for the primary question cannot be quantified from the posted information. The absence of reported analyses is not evidence that the true effects are absent; it is a limit on what can be concluded from this record.
9. Statistical Methods Explained
The registry record specifies a primary outcome based on a dose-limiting toxicity rule, but it does not report the statistical methods used to analyze that outcome. No analyses are listed. The explanation below distinguishes the stated endpoint from general statistical principles; it does not infer an unreported protocol or analysis plan.
What does the MTD rule mean?
The record defines the maximum tolerated dose as the dose preceding one at which at least 2 out of 3 patients in the treatment group experience a DLT. This is a threshold rule: the outcome depends on the observed DLT status at dose levels and on how the study applies the rule. The record names the toxicity criteria, but it does not describe the actual sequence of dose assignments, whether participants could be replaced, or how incomplete observation was handled. Without those details and the observed DLT counts, the rule cannot be applied independently to identify an MTD.
In general, dose-finding rules trade off information about toxicity against the need to avoid exposing too many participants to doses that may be poorly tolerated. A rule based on a small group’s observed events can be sensitive to a single participant’s outcome. The threshold is a design decision, not a guarantee that the selected dose has a precisely known toxicity probability. The registry record does not report a model-based dose-toxicity analysis or any estimate of the probability of DLT at a given dose.
What can be learned from the group counts?
The adverse-event record gives group-specific counts of participants at risk and affected. Such counts are descriptive: they state how many people in each listed group are recorded in each category. They do not, by themselves, identify when events occurred, whether participants had multiple events, how long participants were followed, or whether events led to treatment changes. The record gives no event-level data or follow-up distribution for these safety summaries.
General statistical explanation: with small groups, a count can change substantially as a proportion of the group when even a single participant’s status differs. This makes estimates imprecise and limits the reliability of comparisons across groups. When group assignment is not randomized, statistical adjustment may address measured differences only if the relevant covariates and an appropriate analysis are available; it cannot guarantee removal of unmeasured differences. No such adjustment is reported in the registry record.
Why do analysis details matter?
For an MTD outcome, analysis details include the population used, the evaluability definition, the toxicity observation window, and the handling of missing or incomplete assessments. They also include how the dose levels were ordered and how a result was selected if the observed pattern did not fit the threshold rule neatly. These details affect which observations contribute to the decision. The registry record reports a timeframe of up to 1 month and defines DLTs, but the other details are not reported in the registry record.
In general, an analysis population states which participants are included in a particular estimate. An intention-to-treat population, for example, is often defined by assignment, while a safety population is often defined by treatment received; these are general concepts, not populations identified for this trial. The registry record does not define the primary-outcome analysis population or state whether all enrolled participants were included in the MTD evaluation. The at-risk counts in the adverse-event record should not be assumed to establish the population used for the primary endpoint.
What does the planning illustration represent?
The record describes sample-size planning assumptions as 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 stated fraction of an observed effect. It further states that time-to-event planning uses a total number of events under the Schoenfeld method, while other planning outputs are participants per arm. These are described as planning illustrations based on an observed effect, not as the trial’s own design. The registry record does not report numerical sample-size outputs in the registry record for this analysis.
General statistical explanation: a planning calculation estimates how much information a future comparison might need under specified assumptions. Its result depends on the assumed effect, variability, significance level, allocation, and model. It is not observed power, and it does not show that a completed study had adequate power. The equal-allocation assumption in this illustration also does not describe the listed non-randomized dose groups. The record does not establish that the trial was designed around this calculation.
Over-dispersion is a general concern when count variability exceeds the assumptions of a simple count model. If present, it can make standard errors too small and confidence intervals too narrow unless the model accounts for the extra variation. The registry record does not report a count model or an over-dispersion assessment; this concept therefore does not describe a reported analysis from this study.
Finally, precision should be evaluated from estimates and their uncertainty, not from a significance test alone. No primary-outcome estimate, confidence interval, or analysis result is reported in the registry record. Without those quantities, readers cannot assess the precision of the MTD determination or reproduce an analysis of the primary outcome.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists two outcome measures and no analyses. It does not report a statistical analysis plan describing how the primary and other outcomes were prioritized, whether multiple hypotheses were tested, or whether any adjustment for multiplicity was planned. Multiplicity refers generally to the increased chance of at least one false-positive finding when many statistical tests are conducted. That concern cannot be evaluated from a record with no posted analysis results, and no correction method should be inferred.
Missing-data procedures are not reported in the registry record. The record does not say how participants with incomplete toxicity observation, early discontinuation, or unevaluable outcomes were handled. It also does not report the number assessed for the primary endpoint. These omissions matter because the MTD rule depends on observed DLT status at the dose levels. If some participants lack complete assessment, the way they are classified or excluded can affect the dose-finding conclusion. This is a general methodological concern, not a claim that missing outcome data occurred.
Analysis populations are also not defined. The adverse-event groups include participants listed as at risk, but the registry record does not state that these counts represent the primary-endpoint population or specify whether the groups include everyone enrolled at each dose. The total enrollment is 17, while the record does not explain the relationship between enrollment and the group-specific risk counts. No participant flow or reasons for any difference are reported.
Accordingly, the record does not support an assessment of multiplicity control, missing-data bias, or the exact population underlying the primary endpoint. These are unreported analysis details, not evidence of a particular problem in the trial’s conduct.
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 |
|---|---|---|---|
| Irinotecan&Temsirolimus:Arm 1, Level 1 | 0 | 6 | 0.0% |
| Irinotecan&Temsirolimus:Arm 1, Level 2 | 0 | 8 | 0.0% |
| Irinotecan&Temsirolimus:Arm 2, Level 1 | 0 | 3 | 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 |
|---|---|
| Irinotecan&Temsirolimus:Arm 1, Level 1 | 6 of 6 |
| Irinotecan&Temsirolimus:Arm 1, Level 2 | 8 of 8 |
| Irinotecan&Temsirolimus:Arm 2, Level 1 | 3 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Irinotecan&Temsirolimus:Arm 1, Level 1 | Irinotecan&Temsirolimus:Arm 1, Level 2 | Irinotecan&Temsirolimus:Arm 2, Level 1 |
|---|---|---|---|---|
| Lymphocytes decreased | Blood and lymphatic system disorders | 0 of 6 | 8 of 8 | 2 of 3 |
| Hyperglycemia | Investigations | 2 of 6 | 6 of 8 | 2 of 3 |
| Leukocytes decreased | Blood and lymphatic system disorders | 1 of 6 | 6 of 8 | 2 of 3 |
| Fatigue | General disorders | 4 of 6 | 3 of 8 | 2 of 3 |
| Nausea | Gastrointestinal disorders | 2 of 6 | 4 of 8 | 2 of 3 |
| Neutrophils decreased | Blood and lymphatic system disorders | 2 of 6 | 2 of 8 | 2 of 3 |
| Platelets decreased | Blood and lymphatic system disorders | 3 of 6 | 2 of 8 | 1 of 3 |
| Anorexia (Loss of appetite) | Gastrointestinal disorders | 2 of 6 | 1 of 8 | 2 of 3 |
| Diarrhea | Gastrointestinal disorders | 1 of 6 | 3 of 8 | 1 of 3 |
| Vomiting | Gastrointestinal disorders | 0 of 6 | 2 of 8 | 3 of 3 |
The adverse-event record lists 0 serious events among 6 participants at risk in the first dose group, 0 among 8 in the second, and 0 among 3 in the third. It lists no serious adverse-event terms. For other adverse events, the corresponding affected counts are 6 of 6, 8 of 8, and 3 of 3. These figures are counts within the registry’s groups, not comparative estimates from a randomized safety analysis.
The serious-event counts should be read as the posted counts for the groups and period represented by the record. The record does not provide participant-level event details, event timing, duration of exposure, severity breakdowns for the other-event category, or adjusted rates. It also does not establish whether the same person experienced multiple events. The counts therefore cannot describe the full pattern or burden of toxicity in detail.
Deaths are listed as null rather than as a numeric zero. Deaths are therefore not reported in the registry record; a null entry should not be interpreted as confirming that none occurred. Likewise, the absence of serious-event terms means no terms are listed in the record, not that every potential serious toxicity was specifically ruled out. The posted safety figures are descriptive and do not establish a causal comparison between dose groups.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study was registered as a Phase I, non-randomized, single-group investigation of intravenous irinotecan and temsirolimus in refractory sarcomas. It identifies three dose levels, a stated MTD objective, and a DLT definition. It also reports group-specific adverse-event counts and a status of terminated. These details help characterize the intended study and the available descriptive safety information.
The record does not report a numeric MTD, DLT counts, primary-outcome analyses, or confidence intervals. It therefore does not establish which dose met the MTD rule or how precisely that dose was identified. The listed adverse-event counts do not resolve the primary dose-finding question. Null death entries do not establish zero deaths, and the lack of serious-event terms does not provide a complete account of all possible toxicities.
The study design also limits comparative interpretation. The groups were not randomized, and no control group is described. The dose combinations differ across levels, so differences between groups could not be attributed to a single dose component without further design and analysis information. The record does not report adjusted analyses or participant characteristics that would help assess group comparability.
General statistical explanation: a result can be compatible with a range of underlying values, especially when the available groups are small. Precision depends on the amount and quality of information and is best assessed through an estimate with an uncertainty interval. Since the primary estimate and its uncertainty are not reported, readers cannot tell whether any potential dose conclusion would be precise or stable.
These limits do not show that the combination is effective or ineffective, nor do they establish that a particular dose is safe or unsafe. They define what can and cannot be concluded from the posted registry information: the study’s stated objective and design are visible, but the primary dose-finding result and its statistical support are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial matters statistically because it illustrates the distinction between a registered objective and a reported result. The record gives a defined primary endpoint—a toxicity-based MTD rule—and describes several dose combinations. Yet it does not report the numerical MTD outcome or analyses needed to evaluate how the rule was applied. A clearly stated endpoint is important, but it is not a substitute for outcome data and analysis details.
The design also makes the comparison structure important. Non-randomized dose groups are not interchangeable with randomized treatment arms. Even when group-specific event counts are available, differences may reflect differences between participants or other factors, not solely dose. Here, the dose combinations do not vary in a way that isolates one drug component across all groups. The record reports no adjusted comparisons that could address measured differences.
The adverse-event summaries offer descriptive counts, but they do not contain the detail required for an in-depth safety analysis. The serious-event counts are zero in each listed group, while other adverse events are recorded for every participant at risk in those groups. Death counts are not reported. Keeping those categories distinct avoids treating a missing value as a zero or over-reading an aggregate count.
More broadly, the record demonstrates why early-phase results need information about dose assignment, evaluability, observation windows, participant flow, and uncertainty. Those details help readers distinguish a dose decision from a precise estimate and determine which participants contributed to it. In their absence, the MTD rule can be described, but its outcome cannot be independently assessed. That is a statistical reporting limitation, not a conclusion about the clinical value of the regimen.
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.
Several limitations specific to this record constrain interpretation. The primary endpoint is defined, but its numeric result and the underlying DLT counts are not reported in the registry record. No analyses are listed, so there is no posted estimate, uncertainty interval, or statistical output to evaluate. It is not possible to determine from the record whether the MTD rule was met, how dose decisions were made, or whether all relevant participants had complete toxicity assessment.
The study is classified as non-randomized and single-group, with no control group described. The dose groups therefore do not support a randomized treatment comparison. The listed combination doses vary across levels, and the record does not provide participant characteristics or adjusted analyses that could clarify differences between groups. The record also contains an inconsistency in the third intervention’s arm and level labeling: its intervention name and its description identify different labels. The information does not resolve that discrepancy.
There is no reported protocol-level sample-size justification, analysis plan, participant flow, missing-data procedure, or definition of the primary analysis population. The record’s planning assumptions describe an illustration rather than the trial’s own design, and no numerical planning outputs are available in the registry record for this analysis. It is therefore not possible to use those assumptions to assess the trial’s achieved precision.
Safety summaries are limited to aggregate counts. They do not report event-level details, timing, exposure, or deaths as a numeric count. The status is terminated, but the reason for termination and its implications for data collection are not reported. These limitations make the record informative about the planned question and some reported safety categories, but insufficient for a complete assessment of the dose-finding result.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase I/II Study of Irinotecan and Temsirolimus in Patients With Refractory Sarcomas — NCT00996346.
- Registry record last updated 2015-09-01; status last verified 2015-08.
- Results first posted 2015-09-01.
- 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
NCT00996346 is registered as a Phase I, non-randomized, unmasked, single-group study of irinotecan and temsirolimus in patients with refractory sarcomas. Enrollment is listed as 17; the study started in 2009-10, had primary completion in 2011-11, and is listed as terminated. The stated primary outcome is the maximum tolerated dose of irinotecan, defined using specified dose-limiting toxicities and a timeframe of up to 1 month.
Three dose combinations are described, with weekly intravenous dosing for three consecutive doses followed by one week of rest; one cycle is four weeks. The registry reports group-specific serious and other adverse-event counts, but no primary-outcome analyses. The numeric MTD, DLT counts, analysis populations, and reason for termination are not reported in the registry record. The safety counts are descriptive and do not create a randomized comparison.