Cixutumumab and Temsirolimus in Treating Patients With Metastatic Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cixutumumab and Temsirolimus in Treating Patients With Metastatic Prostate Cancer (NCT01026623), a na phase 1, phase 2 study. The primary outcome is cTTP.

2. Clinical Question

The trial examined cixutumumab given with temsirolimus in patients with metastatic castration-resistant prostate cancer. Its stated aims included studying side effects and assessing how well the combination worked. The registry describes a phase I/II study, but the Phase II portion did not occur, and the planned primary outcome has no data to report.

Accordingly, the posted record does not answer whether the combination changes time to progression. It documents a study plan, treatment description, and adverse-event figures for dose groups, but it does not report an analyzed primary endpoint. The registry lists 16 enrolled participants; that figure alone does not establish how many contributed to any particular outcome analysis. The population description also does not establish that every enrolled participant had each condition listed in the record.

3. Trial Design

The registry classifies NCT01026623 as a phase I/II, single-group trial with no masking. Allocation is listed as NA. It records 16 participants enrolled and a completed status. The recorded start is 2009-10, and primary completion is 2013-02. The sponsor is the National Cancer Institute (NCI).

The treatment arm description specifies cixutumumab and temsirolimus administered intravenously on days 1, 8, 15, and 22. Cixutumumab was administered over 60-70 minutes and temsirolimus over 30 minutes. Courses were to repeat every 28 days in the absence of disease progression or unacceptable toxicity. The registry names three dose groups in its adverse-event record: IMC-A12: 6mg/kg Temsirolimus 20 mg; IMC-A12: 6 mg/kg Temsirolimus 25 mg; and IMC-A12: 20 mg/kg Temsirolimus 20 mg.

Those groups do not constitute a randomized comparison. The registry does not describe a separate control treatment or an allocation process for comparing the doses. It would therefore be inappropriate to interpret differences across the groups as controlled estimates of comparative treatment effects. The record describes a phase I/II trial, but explicitly states that the Phase II portion, to which the primary outcome belongs, did not occur.

The treatment description includes a condition for continuing courses, but the registry does not report individual treatment exposure, adherence, reasons for stopping, or dose modifications. The overall status of completed does not mean that the planned primary outcome was available: the registry says all patients had withdrawn before data analysis. Further details of the protocol, including the rationale for the chosen doses and the intended sample-size justification, are not reported in the registry record.

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

Analysis population for the primary outcome, as defined in the registry: All patients had withdrawn from study prior to data analysis. This Outcome Measure is related to the Phase II portion of the Trial, which did not occur. Therefore, there is no data to report.

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.

6. Primary Endpoint

The registry lists the primary outcome as cTTP, measured over Up to 4 weeks after completion of study treatment.

The planned primary endpoint, cTTP, is a time-to-event measure. The registry defines it as the time from the first day of treatment to the earliest of several progression-related events: tumor progression by RECIST; unequivocal progression by bone scan, defined as at least two new lesions with confirmation at subsequent imaging; new skeletal events; symptomatic progression; or other clinical events attributable to prostate cancer that necessitate major interventions.

In general, a time-to-event endpoint captures both whether an event occurs and how long it takes to occur. It can be useful when the timing of progression is important and participants may have different lengths of follow-up. The definition of the event matters because it determines which clinical developments count as progression. This endpoint combines imaging findings with clinical events, as described in the registry definition.

The registry gives the timeframe as up to 4 weeks after completion of study treatment. However, cTTP is assigned to the Phase II portion, which did not occur. The record states that all patients had withdrawn before data analysis and that there is no data to report for this outcome. Therefore, there is no reported cTTP estimate, event count, or analysis from which to assess the timing of progression. The endpoint’s definition describes what was intended to be measured, not an observed treatment result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a single-group phase I/II study with no masking and no randomized control comparison. It lists 16 enrolled participants and three dose groups in the adverse-event record. These design details shape what can be concluded: adverse-event counts can be described within each recorded group, but the design does not supply a randomized comparison for estimating a treatment difference between groups.

What does a time-to-event endpoint measure?

In general, a time-to-event endpoint records the interval from a defined starting point to a specified event. For cTTP, the registry sets the starting point as the first day of treatment and defines several progression events that can end the interval. Such endpoints can account for both event occurrence and event timing. Their interpretation depends on consistent event definitions, ascertainment, and follow-up. The registry supplies the intended definition and a timeframe of up to 4 weeks after completion of study treatment, but reports no cTTP data.

In general, time-to-event analyses may also account for participants whose event has not been observed by the end of follow-up through censoring. Censoring requires information about each participant’s follow-up and event status. Those participant-level details and any time-to-event analysis are not reported in the registry record. Because the Phase II portion did not occur and all patients had withdrawn before data analysis, no such analysis can be interpreted from the posted results.

What do the adverse-event counts describe?

The serious-event figures report how many participants were at risk and how many were affected in each dose group. In general, counts and proportions describe observed events in the recorded group, while a causal treatment effect requires a suitable comparison and attention to differences in participant characteristics, exposure, and follow-up. This trial is recorded as single-group, and the dose groups are not a like-for-like control comparison. Accordingly, the counts should be read descriptively rather than as evidence that a dose caused a difference in risk.

The registry gives serious-event counts of 3 affected among 6 at risk, 1 among 5, and 1 among 5, respectively. It also reports counts in an “other” adverse-event category. These figures do not provide event timing, duration, recurrence, severity beyond the serious-event classification, or each participant’s treatment exposure. Those details are not reported in the registry record. The listed percentages for top serious terms should be retained as reported; the record does not give their term-specific denominators in the available information.

What do uncertainty and significance usually mean?

General statistical context: a confidence interval describes a range of values compatible with an estimate under the analysis assumptions. Its width conveys precision, and its interpretation depends on the data and method used. A p-value is a measure calculated under a specified statistical model and null hypothesis; it is not the probability that a treatment works or that a result occurred by chance. Neither an interval nor a p-value for cTTP is reported in the registry record, so there is no primary-outcome estimate whose precision or statistical significance can be assessed.

General statistical context: over-dispersion arises when observed variability is greater than a model’s assumptions allow. If it is ignored in an applicable analysis, uncertainty may be understated. The registry does not report a statistical model for the primary endpoint or other analyses, so over-dispersion is not a documented issue in this trial’s posted results. It would be speculative to claim that a particular model or correction was used.

How should planning calculations be understood?

The registry’s sample-size assumptions describe a planning illustration computed from an observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The record distinguishes time-to-event calculations, which give a total number of events, from other calculations, which give participants per arm. These assumptions do not establish that the trial used a two-arm design: the study is recorded as single-group, with no randomized control comparison.

General statistical context: a planning calculation estimates the sample size or event count associated with selected assumptions. It is not observed power, and it does not show that a completed study had a particular probability of detecting an effect. A calculation based on an observed effect is especially dependent on that effect estimate and the assumptions used. The record does not provide the values of the planning illustrations in the registry record described for this analysis, so no sample-size figure or implication can be stated. The trial’s own sample-size justification and statistical analysis plan are not reported in the registry record.

The record lists zero analyses. That means the posted information does not include an analysis result to evaluate for model choice, adjustment, confidence intervals, or hypothesis testing. It is not appropriate to infer those methods from the outcome definition or from the planning assumptions alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies seven outcome measures and lists secondary outcomes including change in PSA doubling time, duration of effect, maximal percentage change in serum PSA as compared to Week 12 versus baseline, progression-free survival, and rate of adverse events according to NCI CTCAE Version 4.0. It lists zero analyses. The primary cTTP outcome belongs to the Phase II portion, which did not occur, and the registry states that all patients withdrew before data analysis.

Multiplicity arises in general when several outcomes, time points, groups, or statistical tests are examined. If many tests are conducted, the chance of at least one apparently notable result can increase unless the analysis plan accounts for that. The record does not report a multiplicity strategy or a statistical analysis plan. Since no analyses are listed, there are no posted tests to assess for multiplicity adjustment. It would be inappropriate to assume either that adjustment was or was not performed outside the information in the record.

The withdrawal statement leaves the analysis population unclear for the planned outcomes. In general, missing outcome data can reduce precision and can bias results when the chance of missingness is related to participant status or outcome. Assessing that possibility requires information about who withdrew, when they withdrew, why they withdrew, and what outcome information remained available. Those details are not reported in the registry record. No analysis population definition, missing-data method, or sensitivity analysis is reported.

These limitations mean that neither completeness nor representativeness of an analyzed outcome population can be assessed from the posted record. The enrollment figure does not substitute for an endpoint-specific denominator. Nor does completed study status establish that planned outcome analyses were completed: the record explicitly says there is no primary outcome data to report.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lipase increased (33.3%), serum amylase increased (20.0%), optic nerve disorder (20.0%), confusion (16.7%), dizziness (16.7%).

The serious adverse-event figures are counts of participants affected and at risk within each recorded dose group. The IMC-A12: 6mg/kg Temsirolimus 20 mg group has 3 affected and 6 at risk; the IMC-A12: 6 mg/kg Temsirolimus 25 mg group has 1 affected and 5 at risk; and the IMC-A12: 20 mg/kg Temsirolimus 20 mg group has 1 affected and 5 at risk. These figures describe the registry’s reported groups and should not be treated as a controlled comparison of dose-related risk.

The “other” adverse-event category lists 6 affected and 6 at risk, 5 affected and 5 at risk, and 3 affected and 5 at risk across those same groups. The registry record does not further define that category in the information. It identifies lipase increased at 33.3%, serum amylase increased and optic nerve disorder at 20.0% each, and confusion, dizziness, and hypertension at 16.7% each among top serious terms. The denominator for each term percentage is not reported in the registry record.

Deaths are not reported in the registry record. Counts alone do not describe event timing, duration, recurrence, or individual treatment exposure. The figures are safety descriptions, not evidence of a causal difference between groups.

12. What the Result Does, and Does Not, Mean

The posted record establishes that a phase I/II trial of cixutumumab with temsirolimus was registered for metastatic prostate cancer, with 16 participants enrolled and three dose groups represented in the adverse-event record. It also provides the intended definition of cTTP and descriptive safety counts. These registry entries describe the study and the information recorded about it; they do not establish a primary efficacy result.

The primary outcome cannot support an estimate of time to progression because the registry says the Phase II portion did not occur and there is no data to report. All patients had withdrawn before data analysis. This is not evidence that cTTP was unchanged, nor is it evidence of benefit. The primary result is unavailable in the registry record. There is also no reported analysis for the listed secondary outcomes.

The adverse-event counts and percentages document reported events in the specified groups. They do not prove that cixutumumab, temsirolimus, or a particular dose caused an event. The trial is not a randomized comparison, and the registry does not describe a control group. The numbers therefore cannot establish comparative safety or rank the dose groups reliably. Deaths are not reported in the registry record, which should not be interpreted as a statement that no deaths occurred.

In general, a study result needs an analyzed outcome, a clear population, and information about uncertainty to show how precisely an effect has been estimated. Those elements are not available for the primary endpoint in this record. The enrollment count and the planning assumptions do not replace an observed result. The sample-size calculations are described as planning illustrations, not as evidence of achieved power or trial findings.

The appropriate statistical reading is therefore limited: the registry documents the trial design, treatment schedule, intended primary measure, and some adverse-event information, while leaving the principal planned outcome without data. Conclusions about treatment effect, comparative risk, or precision cannot be drawn from the posted results.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between a registered endpoint and an analyzed endpoint. The registry gives a detailed cTTP definition, including imaging and clinical progression events, yet also states that the Phase II portion did not occur and that no data are available for that outcome. A well-defined endpoint is necessary for interpretable analysis, but a definition alone is not a result.

The record also shows why design labels matter when reading group-specific event counts. Although three dose groups appear in the adverse-event record, the study is classified as single-group, with allocation listed as NA and no masking. The record cautions that the arms are not a like-for-like control comparison. Descriptive counts can convey what was recorded in each group, but they do not create a randomized estimate of comparative treatment effect.

Another statistical lesson concerns the difference between enrollment and analysis. The registry reports 16 enrolled participants, but also says all patients had withdrawn before data analysis. An enrollment total cannot tell a reader how many contributed to a specific endpoint or whether missing outcomes could affect interpretation. Endpoint-specific denominators and withdrawal details matter for judging completeness and precision; they are not reported for cTTP.

Finally, planning assumptions should not be confused with observed evidence. The record describes a sample-size illustration based on an observed effect and specified assumptions, but identifies it as a planning calculation rather than the trial’s own design. Such calculations do not compensate for the absence of a primary outcome analysis. Together, these features make the record a useful example of how trial structure, outcome availability, and analysis reporting determine what can and cannot be concluded statistically.

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 main limitation is the absence of the planned primary outcome. The registry says cTTP was related to the Phase II portion, which did not occur, and that there is no data to report. It also states that all patients had withdrawn before data analysis. As a result, the primary endpoint’s event count, estimate, and precision are not available.

Withdrawal reasons, timing, and endpoint-specific follow-up are not reported in the registry record. Without these details, missingness cannot be characterized, and the number enrolled cannot be used as the denominator for a cTTP analysis. No analysis population or missing-data approach is reported. The record lists zero analyses, so no primary or secondary statistical result is available to evaluate.

The single-group classification and absence of a randomized control comparison limit interpretation of the dose-group adverse-event figures. The group counts are descriptive and cannot establish comparative effects. The registry does not report participant-level exposure, event timing, or further details about the “other” adverse-event category. Deaths are not reported in the registry record.

The record’s sample-size assumptions are for a planning illustration, not the trial’s own design. The trial’s sample-size justification, statistical plan, and any interim analyses are not reported in the registry record. The study’s completed status should not be taken to mean that the planned Phase II endpoint was analyzed, since the record explicitly says otherwise. These limitations restrict conclusions to the design and descriptive information that the registry documents.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cixutumumab and Temsirolimus in Treating Patients With Metastatic Prostate Cancer — NCT01026623.
• Registry record last updated 2019-06-17; status last verified 2019-05.
• Results first posted 2019-06-17.
• 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.

18. Record Summary

NCT01026623 is recorded as a completed phase I/II, single-group trial of cixutumumab with temsirolimus in metastatic prostate cancer. The registry lists 16 participants enrolled, no masking, and no randomized control comparison. Treatment was described as intravenous administration on days 1, 8, 15, and 22, with courses repeating every 28 days when there was no progression or unacceptable toxicity.

The planned primary endpoint was cTTP, defined using imaging and clinical progression events. It was assigned to the Phase II portion, which did not occur; all patients had withdrawn before data analysis, and the registry reports no primary outcome data. Zero analyses are listed. Descriptive adverse-event counts are recorded for three dose groups, while deaths are not reported in the registry record. The posted information does not establish a treatment effect or a comparative safety conclusion.