A Phase II Study of Oral Cyclophosphamide and Sirolimus (OCR) in Advanced Sarcoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Study of Oral Cyclophosphamide and Sirolimus (OCR) in Advanced Sarcoma (NCT00743509), a non-randomized phase 2 study. The primary outcome is Number of Patients Alive Without Disease Progression.

2. Clinical Question

3. Trial Design

This was a Phase II, non-randomized, single-group study with no masking. The registry lists an enrollment of 49 and describes treatment with oral cyclophosphamide and sirolimus in 28 day cycles. The study was sponsored by University of Michigan Rogel Cancer Center. The recorded start is 2008-08, the primary completion is 2010-04, and the status is completed.

The brief summary describes patients with relapsed or widespread sarcoma whose disease could not be cured by surgery, radiation, or conventional chemotherapy. The registry’s condition listing is osteosarcoma. The record does not report the enrolled participants’ detailed disease characteristics or explain how the condition listing relates to the broader wording in the study summary.

Because there was one treatment group and no random allocation, outcomes in the treated group cannot be contrasted with outcomes in a concurrent control group. Observed changes or events during the study would not, by themselves, identify what would have happened to the same patients under another treatment or without OCR. This is a design limitation, not a conclusion about the treatment’s effects.

The primary outcome was a count of patients alive without disease progression at 6 months among those evaluable for response. Median overall survival time is listed as a secondary outcome. The registry record does not report results for either outcome in the information, and it does not report the statistical analysis plan. It also does not report why the enrollment target was selected or whether the study used interim analyses.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Eligible participants previously treated with chemotherapy underwent screening. Fifty-one patients were consented, 49 enrolled.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients that tolerated and completed at least one 28 day cycle of therapy were considered evaluable

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 Number of Patients Alive Without Disease Progression, measured over 6 months.

The primary endpoint is the number of evaluable patients who were alive and without evidence of sarcoma progression at 6 months. The registry defines evaluability as tolerating and completing at least one 28 day cycle of therapy. It describes progression using changes in target lesions, unequivocal progression of non-target lesions, or appearance of new tumor lesions greater than 10mm. Target lesions followed were lesions that had progressed by World Health Organization criteria.

A count at a specified follow-up time is a binary-outcome measure: each evaluable patient either meets the endpoint definition or does not. Such an endpoint can provide a direct description of how many patients meet a clinically interpretable status at the stated time. It also depends on consistent outcome assessment and a clearly defined analysis population. Restricting the endpoint to evaluable patients means it does not automatically describe every enrolled participant.

The registry record does not report the observed count or the number of evaluable patients. It therefore does not support an estimate of the endpoint proportion, its precision, or a comparison with a benchmark. No conclusion about the primary endpoint’s magnitude can be drawn from its definition alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary outcome expressed as a count: a patient either meets the stated condition at 6 months or does not. A count is not interpretable on its own without knowing the relevant analysis population. Here, the record says patients had to tolerate and complete at least one 28 day cycle to be considered evaluable. It does not report how many participants met that definition, how many were assessed at 6 months, or how missing assessments were handled.

In general, an estimate of a binary outcome’s frequency is paired with an interval that conveys statistical uncertainty. A confidence interval describes a range of values compatible with the data under the method’s assumptions; it does not account automatically for every source of bias or make a single-group study comparative. No interval or method for estimating one is reported for this primary endpoint. Since neither the count nor its denominator is reported, there is no primary endpoint estimate to interpret.

The endpoint uses a disease-progression definition based on target and non-target lesions and new lesions. This makes the rules for assessment important: the same definitions and assessment approach need to be applied consistently for the endpoint to be interpretable. The registry record states that target lesions followed were lesions that had progressed by World Health Organization criteria, and it describes progression as a 25% or greater increase in the sum of the product of target lesions, unequivocal progression of non-target lesions, or appearance of new tumor lesions greater than 10mm. The registry does not report further details about assessment schedules, adjudication, or handling of uncertain assessments.

The design is single-group and non-randomized. In general, random allocation can help balance measured and unmeasured prognostic factors between comparison groups, while a concurrent control can show outcomes under a different study condition. Neither feature is present. A single-group count can describe what happened among the assessed participants, but it does not isolate the effect of treatment from disease course, participant selection, or other influences. The registry record does not report a prespecified historical benchmark or a statistical comparison against one.

The record lists median overall survival time as a secondary outcome. Time-to-event methods generally account for the timing of events and for participants whose event status is not observed through the full follow-up period. Their interpretation depends on how event times, censoring, follow-up, and the analysis population are defined. Those details and the median result are not reported in the registry record, so no survival analysis can be reconstructed from the information listed.

The registry also reports safety counts and percentages. In general, a count of participants with an event and a count of events are different quantities: one participant may experience more than one event. The record’s wording and listed figures describe participants affected, but it does not provide event-level detail or explain whether repeated events were counted separately in each category. Percentages describe the reported frequency in the specified group; they do not establish causation. In a single-group study, there is no randomized safety comparison to separate treatment-associated events from events that might occur because of disease or other circumstances.

The sample-size assumptions describe a planning illustration, not the study’s original design justification. The illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a fraction of an observed effect. For binary outcomes, the stated convention is participants per arm; time-to-event planning uses total events. These are hypothetical planning conditions and do not describe the actual single-group design. The record does not report the protocol’s sample-size justification, target effect, or statistical plan. Any illustrated sample size is a planning quantity, not observed power.

No multiplicity procedure, interim analysis, or handling of multiple outcomes is reported in the registry record. General statistical practice distinguishes a prespecified primary outcome from secondary or exploratory outcomes because interpreting several tests can raise the chance of a false-positive finding. That general concern does not show that a particular adjustment was required or omitted in the study; the relevant plan is not reported.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Oral Cyclophosphamide and Sirolimus (OCR)")
n      <- c(47)
events <- c(10)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Oral Cyclophosphamide and Sirolimus (OCR)  47  10  21.3  10.7  35.7  12.0  34.9  12.0  35.0

11. Multiplicity, Missing Data and Analysis Populations

The record identifies one primary endpoint and lists median overall survival time as a secondary outcome. It also reports 2 outcome measures and 0 analyses. The registry record does not report a multiplicity strategy, such as a hierarchy among outcomes or an adjustment for multiple statistical tests. It does not report whether interim analyses were planned or performed. These details should not be inferred from the outcome list alone.

The primary endpoint population is described as patients who tolerated and completed at least one 28 day cycle. The registry record does not report how many participants met this definition, how many had outcome assessments at 6 months, or how participants without an assessment were treated in the analysis. It also does not describe imputation, sensitivity analyses, or other missing-data procedures. The reported enrollment of 49 therefore should not be treated as the primary endpoint denominator.

In general, missing outcome data can affect both the estimate and its precision, particularly if the likelihood of missingness is related to health status or outcome. The registry record does not provide enough information to evaluate whether missingness occurred or how it might affect the result. No primary endpoint count or analysis result is reported, so neither the handling of missing data nor the effect of missingness can be assessed.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fever (8.2%), death (4.1%), infection with grade 3 or 4 neutrophils (4.1%), dyspnea (shortness of breath) (4.1%), thrombosis/thrombus/embolism (4.1%).

The safety record lists 49 participants at risk for serious adverse events and 17 affected. It lists 49 at risk for other adverse events and 36 affected. The most frequently listed serious-event term is Fever at 8.2%. Death, Infection with Grade 3 or 4 neutrophils, Dyspnea (shortness of breath), and Thrombosis/thrombus/embolism are each listed at 4.1%; Hypotension is listed at 2.0%.

These figures describe reported events in the OCR group. They are not a comparison against another treatment, and they do not establish that OCR caused a particular event. A serious adverse event term is not the same thing as a separate mortality analysis. Although Death appears among the listed serious-event terms, a separate deaths count is not reported in the registry record. The record does not provide additional details about event timing, duration, recurrence, or attribution.

In general, safety counts and percentages should be read with their stated population and event definitions in mind. They do not by themselves describe severity distribution beyond what is named, or show how risks compare across treatments. The study’s single-group design limits comparative safety interpretation.

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

The registry record shows that a Phase II study was conducted in a single group receiving oral cyclophosphamide and sirolimus, with a primary endpoint defined as the number of evaluable patients alive without progression at 6 months. It also records serious and other adverse-event counts and lists median overall survival time as a secondary outcome. These details describe the design and the outcomes the study intended to assess.

The record does not report the primary endpoint count, its evaluable denominator, a confidence interval, or a statistical analysis result. It also does not report the median overall survival result. Consequently, the registry entry cannot establish the observed frequency of being alive without progression at 6 months or the precision of that frequency. It cannot establish an overall-survival estimate from the listed secondary outcome title alone.

Even a reported outcome from this design would be an observation in a non-randomized, single-group study, not a randomized comparison. Without a control group, the study cannot by itself distinguish outcomes associated with treatment from outcomes related to patient selection, disease course, or other influences. The safety counts likewise do not indicate how event frequencies compare with another treatment.

General statistical interpretation separates a study’s question, its design, and the results it reports. A clearly defined endpoint does not substitute for an observed result, and a completed study status does not establish what the result was. Here, the primary result and several analysis details are not reported in the registry record. The available information supports a description of the study design and recorded safety figures, but not a conclusion about treatment benefit or comparative risk.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a registered question and a reported result. Its primary endpoint is defined with a follow-up time, disease-progression criteria, and an evaluability rule. Those details establish what the study intended to count, but the registry record does not include the count, denominator, or uncertainty estimate. The endpoint’s definition alone cannot answer the study question quantitatively.

The single-group, non-randomized design also makes the distinction between description and comparison especially important. A study can report outcomes among treated participants without establishing what would have occurred under a different treatment. Statistical methods cannot create a concurrent comparison that the design did not include. Readers should therefore distinguish a within-group outcome description from an estimate of a treatment contrast.

The safety listing adds another useful interpretive point: reported event frequencies are not causal comparisons. The registry records affected participants and several serious-event terms, but no control group is available to contextualize those frequencies comparatively. The separate mortality outcome is not reported, even though Death is among the listed serious-event terms.

Finally, planning illustrations are distinct from observed evidence. Their stated two-arm assumptions do not match this single-group study, and they are not observed power. The record does not report the original sample-size justification or analysis plan. Together, these features show why a complete statistical interpretation depends on the outcome results, analysis population, missing-data handling, and design context, not merely on a study title or endpoint definition.

15. 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 primary limitation for interpretation is that the registry record does not report the primary endpoint result. The evaluable denominator and the number alive without progression at 6 months are also not reported. Without those values, the endpoint’s frequency and precision cannot be assessed.

The study has no randomized comparator: it is recorded as non-randomized and single-group, with no masking. This limits causal and comparative interpretation. The registry record does not report the protocol’s statistical plan, sample-size justification, interim-analysis approach, or any multiplicity procedure. It also does not report the method used for the listed secondary outcome, median overall survival time.

The primary endpoint applies to patients who tolerated and completed at least one 28 day cycle, rather than necessarily to everyone enrolled. The number meeting that evaluability definition and the handling of missing follow-up are not reported. The condition listing is osteosarcoma, while the study summary describes sarcoma more broadly; the registry record does not provide further detail about the enrolled disease mix.

Safety counts are available, but the registry does not report a comparator, event timing, repeated-event detail, or a separate deaths count. The serious-event term Death should not be treated as a substitute for a reported mortality outcome. These gaps constrain interpretation of both efficacy outcomes and safety findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase II Study of Oral Cyclophosphamide and Sirolimus (OCR) in Advanced Sarcoma — NCT00743509.
• Registry record last updated 2015-09-28; status last verified 2015-08.
• Results first posted 2013-05-22.
• 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.

19. Record Summary

NCT00743509 is recorded as a completed Phase II study sponsored by University of Michigan Rogel Cancer Center. It enrolled 49 participants and evaluated oral cyclophosphamide and sirolimus in a single, non-randomized group without masking. Treatment was described in 28 day cycles. The registry lists osteosarcoma as the condition and describes a broader advanced-sarcoma population in the study summary.

The primary endpoint counted evaluable participants alive without progression at 6 months. Median overall survival time is listed as a secondary outcome. The primary endpoint result, secondary outcome result, analysis methods, and missing-data procedures are not reported in the registry record. Serious adverse events were listed for 17 participants at risk, and other adverse events for 36 participants at risk. The design does not include a control group for comparative interpretation.