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 Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma (NCT00949325), a na phase 1, phase 2 study. The primary outcome is Part 1: Incidence of Dose Limiting Toxicities.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00949325 |
| Phase | Phase 1, Phase 2 |
| Condition | Sarcoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
| Results posted | Yes |
2. Clinical Question
The study asked whether a dosing regimen combining temsirolimus, also called Torisel in the study title, with liposomal doxorubicin could be identified for patients with recurrent sarcoma. Its primary focus was safety during dose escalation. A secondary purpose was to assess the combination’s effectiveness, with outcomes including response and time-to-event measures.
Population
Patients with recurrent sarcoma; the official title describes advanced soft tissue and bone sarcomas. The registry lists sarcoma as the condition and records enrollment of 24 participants.
Intervention
Temsirolimus plus liposomal doxorubicin. The study description specifies dose escalation of temsirolimus with a constant dose of liposomal doxorubicin.
Comparator
There was no separate comparator arm. The registry describes a single-group study and lists allocation as not applicable.
Primary question
What dose-limiting toxicities occurred in each dose cohort by the end of the second 28-day cycle?
The question is therefore not framed as a randomized comparison of the combination against another treatment. The dose cohorts are part of dose escalation, not like-for-like control groups. The secondary outcomes named in the registry include objective response rate, progression-free survival, overall survival, time to response, and pharmacokinetic measures. Naming these outcomes does not establish that numerical results for them are reported.
3. Trial Design
This was a completed phase I/II trial with a single-group design and enrollment of 24 participants. The registry lists no masking and allocation as not applicable. The sponsor was Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. The recorded study start was 2009-09, and primary completion was 2012-09.
The intervention was temsirolimus plus liposomal doxorubicin. The arm description says temsirolimus was escalated by dose cohort while the liposomal doxorubicin dose remained constant. This structure fits the stated primary aim of identifying a safe dosing regimen: observations from dose cohorts inform the safety assessment during escalation. The registry record does not report the cohort sizes, the dose levels tested, or the rules used to move between dose levels.
The primary outcome was the incidence of dose-limiting toxicities, expressed as a number of participants, with a timeframe ending at the end of the second 28-day cycle. The description says toxicities were assessed in each dose cohort. The record does not report a separate control group, and the cohort structure should not be interpreted as a randomized comparison. The stated secondary outcomes cover response, survival, time to response, and drug exposure and clearance.
The design labels alone do not supply a full statistical protocol. The registry record does not report the planned sample-size justification, a detailed analysis plan, the definitions used for dose-limiting toxicity, or whether any interim analyses were planned. It lists 0 analyses. Those omissions limit how specifically the results can be interpreted from the record, even though the study status is completed.
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 | Cohort 1, Dose Level 3 | Cohort 2, Dose Level 4 | Cohort 3, Dose Level 5 |
|---|---|---|---|
| STARTED | 3 | 18 | 3 |
| COMPLETED | 3 | 16 | 3 |
| NOT COMPLETED | 0 | 2 | 0 |
Reasons for not completing this period:
| Reason | Cohort 1, Dose Level 3 | Cohort 2, Dose Level 4 | Cohort 3, Dose Level 5 |
|---|---|---|---|
| Adverse Event | 0 | 2 | 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 | Temsirolimus Plus Liposomal Doxorubicin |
|---|---|---|
| Participants analysed | 24 | |
| Age, Categorical: <=18 years | Participants | 5 |
| Age, Categorical: Between 18 and 65 years | Participants | 17 |
| Age, Categorical: >=65 years | Participants | 2 |
| Age, Continuous | years | 39.5 (9 to 70) |
| Sex: Female, Male: Female | Participants | 14 |
| Sex: Female, Male: Male | Participants | 10 |
| Region of Enrollment: United States | participants | 24 |
6. Primary Endpoint
The registry lists the primary outcome as Part 1: Incidence of Dose Limiting Toxicities, measured over End of second 28-day cycle.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is Part 1: Incidence of Dose Limiting Toxicities. It is recorded as a number of participants, and the registry describes assessment in each dose cohort through the end of the second 28-day cycle. The endpoint is intended to capture participants experiencing toxicities that meet the study’s dose-limiting criteria during the stated assessment period. The criteria themselves are not reported in the registry record.
In general, dose-limiting toxicity is used in dose-escalation research to help assess whether a dose is tolerable within a defined treatment period. Considering the count by cohort can inform the safety evaluation of the dose levels under study. This general purpose does not reveal the study’s specific decision rules, which are not reported in the registry record.
The registry supplies no numerical primary-endpoint results, such as the number of participants with dose-limiting toxicities in each cohort. Consequently, the endpoint definition and timeframe can be described, but the incidence across dose cohorts cannot be interpreted from this record. The overall serious adverse event count is a distinct safety summary and should not be substituted for the primary endpoint: the registry does not state that every serious adverse event met the study’s dose-limiting criteria.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a completed, single-group phase I/II dose-escalation study enrolling 24 participants with recurrent sarcoma. The combination was temsirolimus plus liposomal doxorubicin, with temsirolimus dose escalation and a constant liposomal doxorubicin dose. The primary endpoint was dose-limiting toxicity incidence by cohort through the end of the second 28-day cycle. These design details establish what the trial set out to assess, but the registry record does not report the primary endpoint’s numerical results.
The record lists 7 participants with serious adverse events and 13 with other adverse events, each among 24 participants in the treatment group. These are safety counts for the group, not the dose-limiting toxicity counts by cohort. The record does not report whether any of the listed serious events met the protocol’s definition of a dose-limiting toxicity. It also does not provide a breakdown of the adverse event counts by dose cohort.
The most frequently listed serious adverse event terms are Dyspnea, Plural effusion, and Respiratory failure, each recorded as 8.3%. Pneumothorax, Anorexia, and Fever and chills are each recorded as 4.2%. The registry uses the term Plural effusion; it is reproduced as recorded. The percentages are registry entries, not estimates from a randomized comparison. The record does not report the number of events underlying each term or whether participants could appear under more than one term.
The secondary outcomes include median progression-free survival and mean progression-free survival among subjects treated at the temsirolimus MTD, 20 mg/m^2, objective response rate, mean overall survival among subjects treated at that MTD, time to response, and pharmacokinetic measures. The outcome list identifies what was considered, but numerical estimates for these outcomes are not reported in the registry record. The record lists 0 analyses, so it does not furnish analysis details that would support interpretation of treatment effects or uncertainty.
Because this was a single-group study, there is no randomized control arm for estimating a comparative treatment effect. Changes or outcomes observed within the enrolled group cannot by themselves distinguish a treatment effect from other explanations. In general, a confidence interval describes the statistical uncertainty around an estimate; the registry record does not report confidence intervals for the outcomes. No conclusion about efficacy or comparative safety can be drawn from the outcome names or aggregate adverse event counts alone.
9. Statistical Methods Explained
The statistical methods that can be described are constrained by the registry entries. It identifies a single-group phase I/II study, a dose-escalation intervention, a participant-count primary endpoint, a defined primary-outcome timeframe, and a list of secondary outcomes. It does not report a detailed statistical analysis plan. The record lists 0 analyses, so there are no reported analysis specifications to use when assessing how estimates were obtained.
Why dose escalation matters
In general, a dose-escalation study evaluates safety across dose cohorts as the dose of a study drug changes. Cohorts are groups assigned to dose levels within the escalation scheme; they are not necessarily randomized comparison groups. Here, the registry says temsirolimus was escalated while liposomal doxorubicin remained at a constant dose. It does not report cohort sizes, the sequence of dose levels, the escalation rules, or the protocol’s definition of dose-limiting toxicity. Without those details, the cohort-level safety decision process cannot be reconstructed.
What the primary count represents
The primary outcome is expressed as the number of participants with dose-limiting toxicities in each dose cohort, assessed through the end of the second 28-day cycle. In general, a count gives the number of people meeting a defined event criterion; interpretation depends on the criterion, observation period, and denominator. The registry does not provide the cohort-level counts or denominators, nor does it report the operational definition of a qualifying toxicity. The overall group size does not fill in those missing cohort details.
Single-group interpretation
In general, a randomized comparison helps separate differences associated with treatment assignment from other differences between groups. This study is not described as randomized and has no listed comparator arm. Its safety summaries therefore describe participants receiving the combination, rather than a relative risk against a control treatment. A within-group count cannot establish what would have occurred in a different group under another treatment or under no treatment.
Secondary outcomes and statistical summaries
The registry lists median and mean progression-free survival for subjects treated at the temsirolimus MTD, identified as 20 mg/m^2, along with mean overall survival for subjects treated at that MTD. It also lists objective response rate and time to response. In general, median and mean are different ways to summarize a distribution: the median marks its midpoint, while the mean is an arithmetic average. Time-to-event outcomes also require information about follow-up and censoring for interpretation. Those analysis details and numerical estimates are not reported in the registry record.
Pharmacokinetic outcomes listed are maximum observed plasma concentration, area under the curve, and drug clearance. In general, these measures describe aspects of drug concentration over time and its removal from the body. The outcome list alone does not give their estimates, variability, sampling schedule, or analysis methods. These details are not reported in the registry record.
Planning illustrations are not trial results
The sample-size planning assumptions described with the statistical material use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe illustrations based on fractions of an observed effect, not the trial’s own design or observed power. The illustrations use participants per arm for non-time-to-event outcomes and total events for time-to-event outcomes. These hypothetical two-arm assumptions do not change the fact that the trial itself is recorded as single-group, and no calculated planning values are stated in the registry entries.
Precision and uncertainty
In general, estimates from a small study can be imprecise, and a confidence interval communicates uncertainty around an estimate rather than guaranteeing that the true value lies within a particular observed range. No confidence intervals or numerical primary-outcome estimates are reported in the registry record. The adverse event percentages are recorded as 8.3% and 4.2%; they should be read as descriptive entries, not as comparative estimates or as a complete account of uncertainty.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 12 outcome measures, spanning the primary dose-limiting toxicity endpoint and secondary outcomes such as response, survival, time to response, and pharmacokinetic measures. It lists 0 analyses. The registry record does not report whether the analyses used any adjustment for multiple outcomes, how outcomes were prioritized beyond the designation of a primary endpoint, or whether specific comparisons were prespecified. Without those details, the possibility and handling of multiplicity cannot be assessed.
Missing-data methods are not reported in the registry record. The record does not state how participants who discontinued treatment, missed visits, or lacked outcome assessments were handled. It also does not report the amount or pattern of missing outcome data. These omissions matter because analysis results can depend on which participants contribute data and how incomplete observations are treated.
The analysis populations are not described. The record does not specify whether outcomes were analyzed among all enrolled participants, those who received treatment, or a narrower evaluable group. For the primary endpoint, it does not report cohort denominators or participant-level outcome counts. For the secondary time-to-event and response outcomes, it does not report analysis populations or the handling of follow-up. Thus, the enrollment figure alone should not be mistaken for the denominator used for every outcome.
These gaps do not establish that particular methods were or were not used; they mean the methods are not reported in the registry record. The completed status does not resolve the missing statistical details.
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 |
|---|---|---|---|
| Temsirolimus Plus Liposomal Doxorubicin | 7 | 24 | 29.2% |
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 |
|---|---|
| Temsirolimus Plus Liposomal Doxorubicin | 13 of 24 |
Most frequent serious adverse event terms
| Event term | Organ system | Temsirolimus Plus Liposomal Doxorubicin |
|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 2 of 24 |
| Plural effusion | Respiratory, thoracic and mediastinal disorders | 2 of 24 |
| Respiratory failure | General disorders | 2 of 24 |
| pneumothorax | Respiratory, thoracic and mediastinal disorders | 1 of 24 |
| Anorexia | Gastrointestinal disorders | 1 of 24 |
| Fever and chills | Infections and infestations | 1 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Temsirolimus Plus Liposomal Doxorubicin |
|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 5 of 24 |
| Thrombocytopenia | Blood and lymphatic system disorders | 2 of 24 |
| Hypokalemia | Metabolism and nutrition disorders | 2 of 24 |
| Elevated transaminases | Hepatobiliary disorders | 2 of 24 |
| Stomatitis | Gastrointestinal disorders | 2 of 24 |
| anemia | Blood and lymphatic system disorders | 1 of 24 |
| Hypocalcemia | Metabolism and nutrition disorders | 1 of 24 |
| Hyperlipedemia | Metabolism and nutrition disorders | 1 of 24 |
| Pancreatitis | Hepatobiliary disorders | 1 of 24 |
Serious events with the highest arm-level rate: dyspnea (8.3%), plural effusion (8.3%), respiratory failure (8.3%), pneumothorax (4.2%), anorexia (4.2%).
The registry lists 7 participants with serious adverse events and 13 participants with other adverse events among 24 participants in the Temsirolimus Plus Liposomal Doxorubicin group. These are group-level participant counts. They do not describe how many events each participant experienced, and the record does not say whether the categories overlap. Deaths are not reported in the registry record.
The listed serious adverse event terms are Dyspnea, Plural effusion, and Respiratory failure, each at 8.3%, followed by pneumothorax, Anorexia, and Fever and chills, each at 4.2%. These terms and percentages should be read as registry summaries. The record does not state the event counts underlying the term-specific percentages, the grading criteria, or whether a participant could contribute to more than one term. Plural effusion is the wording in the registry record.
In general, serious adverse events and dose-limiting toxicities are not interchangeable categories: a serious event is classified using seriousness criteria, whereas dose-limiting toxicity depends on the study’s protocol definition. The registry does not report which, if any, serious events were also dose-limiting. The aggregate safety figures therefore do not answer the primary endpoint question about toxicity by dose cohort.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed phase I/II study evaluated temsirolimus plus liposomal doxorubicin in a single group of 24 participants with recurrent sarcoma. The study description specifies temsirolimus dose escalation with a constant liposomal doxorubicin dose. Its primary endpoint was the number of participants with dose-limiting toxicities in each dose cohort through the end of the second 28-day cycle.
The record also reports aggregate safety counts: 7 participants had serious adverse events and 13 had other adverse events. It lists serious event terms and their percentages. These summaries describe reported events in the treatment group; they are not a randomized comparison and do not give dose-limiting toxicity counts by cohort. Deaths are not reported in the registry record.
The registry lists secondary outcomes related to response, progression-free survival, overall survival, time to response, and pharmacokinetics. It does not report numerical results for those outcomes in the available record. Nor does it report a numerical result for the primary endpoint. As a result, the outcome list cannot support a conclusion about the size or precision of a treatment effect.
In general, a single-group design can describe what happened among enrolled participants, but without a control group it cannot isolate the effect of an intervention from other potential explanations. The registry does not provide comparative estimates or confidence intervals. The absence of those estimates should not be converted into a claim of benefit, lack of benefit, or equivalence. The posted information supports a description of the study design and the adverse event summaries, while leaving key efficacy and dose-cohort safety results unreported.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of the distinction between a dose-escalation safety question and a comparative treatment question. Its design is single-group, and its primary endpoint is a participant count within dose cohorts over a specified assessment period. That endpoint aligns with the stated aim of identifying a dosing regimen, but the registry record does not report the cohort-level results needed to interpret the escalation outcome.
The registry also illustrates why adverse event summaries should not be treated as substitutes for a primary endpoint. Serious adverse events are reported for the treatment group, but the record does not identify which events met the study’s dose-limiting criteria. Without the cohort-specific counts, cohort denominators, and toxicity definition, the primary safety question remains unresolved in the record.
For clinical researchers, the study also highlights the difference between naming an outcome and reporting an analyzable result. A list of secondary outcomes identifies intended measures, but estimates, uncertainty, analysis populations, and missing-data handling are needed for statistical interpretation. Those details are not reported in the registry record.
The sample-size illustrations use assumptions for a two-arm comparison, whereas the trial itself is recorded as a single-group study. Keeping planning illustrations separate from the actual design avoids treating a hypothetical calculation as a trial result or as evidence of observed power. In general, statistical interpretation depends not only on outcome labels but also on design, denominators, methods, and reported estimates.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The registry record lacks cohort-level primary outcome results. It does not report the dose-limiting toxicity counts or denominators by cohort, the temsirolimus dose levels, the escalation rules, or the definition of a dose-limiting toxicity. These omissions prevent interpretation of the main safety question and make it impossible to connect the overall adverse event summaries to the dose-escalation endpoint.
The single-group design has no randomized control arm. It therefore does not provide a like-for-like comparison from which to estimate a relative treatment effect. The 24 participants were enrolled in the study overall, but cohort sizes and outcome-specific analysis populations are not reported. The registry record also does not report numerical results for the secondary outcomes, confidence intervals, missing-data methods, or a detailed analysis plan.
The serious adverse event summary gives participant counts and selected terms with percentages, but does not report event counts for each term, grading, overlap between categories, or deaths. The record does not state how many serious events were dose-limiting. The wording Plural effusion is retained as recorded.
The record lists 12 outcome measures and 0 analyses, but does not explain multiplicity handling or which analysis populations were used. These limitations are gaps in the registry record; they do not establish what analyses may have been conducted elsewhere. They constrain what can be concluded from the registry information alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy Study of Torisel and Liposomal Doxorubicin for Patients With Recurrent Sarcoma — NCT00949325.
- Registry record last updated 2019-03-11; status last verified 2019-03.
- Results first posted 2019-03-11.
- 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
NCT00949325 is a completed phase I/II, single-group study of temsirolimus plus liposomal doxorubicin in recurrent sarcoma. Enrollment was 24. The study description specifies escalation of temsirolimus with a constant dose of liposomal doxorubicin. Allocation is listed as not applicable, and masking as none.
The primary outcome was dose-limiting toxicity incidence in each dose cohort through the end of the second 28-day cycle. Numerical results for that endpoint are not reported in the registry record. The record lists 7 participants with serious adverse events and 13 with other adverse events, among 24 participants in the treatment group. It also lists secondary response, survival, time-to-response, and pharmacokinetic outcomes, but their numerical results are not reported in the registry record.
The registry lists 12 outcome measures and 0 analyses. It does not report the dose-limiting toxicity definition, cohort-level results, analysis populations, missing-data methods, or a detailed statistical plan.