A Study of R1507 in Participants With Recurrent or Refractory Sarcoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of R1507 in Participants With Recurrent or Refractory Sarcoma (NCT00642941), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8.

2. Clinical Question

The study was intended to assess objective response, progression-free survival, and safety and tolerability in people with recurrent or refractory sarcoma. Its cohorts separate diagnoses rather than randomizing participants between R1507 and a control treatment. The registry lists an enrollment of 317, but that figure should not be treated as the denominator for the primary endpoint: the analysis population is described separately, and cohort-specific analyzed counts are not reported for the endpoint apart from the note that no participants were analyzed in Cohort 3 because efficacy data were not collected for that cohort.

The endpoint’s response definition distinguishes complete response, meaning disappearance of all known disease, from partial response, defined by a decrease in measured tumor load. These are response categories assessed over time, not a direct comparison of R1507 with another treatment. Because the record contains no response percentage, uncertainty interval, or inferential analysis for this endpoint, it does not support a numerical estimate of response in the listed cohorts.

3. Trial Design

This was a Phase II study with non-randomized allocation, no masking, and a parallel-cohort model. The registry lists Hoffmann-La Roche as the sponsor. The recorded enrollment is 317. The study began on 2007-12-18, had a primary completion date of 2014-02-19, and is marked terminated. The reason for termination is not reported in the registry record.

The cohorts were organized by sarcoma diagnosis. They included primary and secondary Ewing’s sarcoma cohorts, an expanded Ewing’s sarcoma cohort, osteosarcoma, synovial sarcoma, rhabdomyosarcoma, five named less common sarcoma diagnoses, and a cohort with diagnosis not specified. This organization means that the study describes experience across multiple disease groups rather than a single homogeneous population. Cohort membership was not randomized, and the registry explicitly cautions that the arms are not a like-for-like control comparison.

The listed intervention was R1507. Most cohorts were assigned a schedule of 9 mg/kg by intravenous infusion once weekly. The expanded Ewing’s sarcoma cohort used 27 mg/kg every 3 weeks and was described for participants aged 2 to 21 years; the other cohort descriptions specify participants aged 2 years and older. Treatment was described as continuing until an event such as disease progression, unacceptable toxicity, withdrawal, or another specified reason for stopping. The record does not provide cohort-specific treatment exposure or adherence results.

The primary endpoint concerns complete or partial response in Cohorts 2 to 8. The study’s broader outcome list also includes response, progression-free survival, duration of response, time to progression, failure-free survival, overall survival, and adverse events. The registry records 13 outcome measures but no analysis entries. It does not report a randomized comparator, masking, or a statistical analysis plan that would support causal comparisons between cohorts.

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.

Only the first 6 of 12 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT population included all randomized participants who received at least 1 dose of study drug and had at least 1 post baseline efficacy assessment. There were 0 participants analyzed for Cohort 3 due to no efficacy data being collected for that cohort.

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.

Only the first 6 of 13 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Complete or Partial Response, According to World Health Organization (WHO) Criteria in Cohorts 2 to 8, measured over Baseline up to 6 years (assessed at baseline, every 6 weeks for 24 weeks, then every 12 weeks until disease progression).

The primary endpoint is the percentage of participants with complete or partial response according to World Health Organization criteria in Cohorts 2 to 8. Complete response is defined as disappearance of all known disease, confirmed by two consecutive observations not less than 4 weeks apart. Partial response is defined as a decrease of at least 50% in the total tumor load of measured lesions, with consecutive observations not less than 4 weeks apart.

Response endpoints are used to describe whether measurable disease has decreased or disappeared during treatment. The combined complete-or-partial-response measure captures these two categories together; it does not by itself describe how long a response lasts, whether disease later progresses, or how participants fare overall. Those questions are represented separately in the registry’s outcome list through duration of response, progression-free survival, time to progression, failure-free survival, and overall survival.

The stated assessment period runs from baseline up to 6 years, with assessment at baseline and every 6 weeks for 24 weeks, then every 12 weeks until disease progression. The primary endpoint’s numerical percentage and its uncertainty are not reported in the registry record. The record also notes that no participants were analyzed for Cohort 3 because no efficacy data were collected for that cohort.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a response percentage represent?

In general, a response percentage is the number of participants meeting the defined response criterion divided by the number included in the relevant analysis, expressed as a percentage. Its meaning depends on both the response definition and the analysis denominator. The endpoint combines complete response and partial response under World Health Organization criteria. Complete response requires disappearance of known disease confirmed in consecutive observations. Partial response requires a decrease of at least 50% in measured tumor load, also supported by consecutive observations separated by not less than 4 weeks.

The registry does not give the primary endpoint’s response count or analysis denominator. Without those quantities, the percentage cannot be reconstructed or judged for precision. The overall enrollment of 317 is not a substitute for the endpoint denominator, because the stated analysis population has additional eligibility conditions and the number analyzed by cohort is not reported for this endpoint.

How should uncertainty be understood?

In general, a confidence interval describes the range of effect estimates reasonably compatible with the observed data under a specified statistical method. A narrower interval indicates greater precision, while a wider interval indicates less precision. It does not resolve problems such as selection bias, outcome measurement limitations, or the absence of a suitable comparison group. The registry record does not report a confidence interval for the primary response endpoint, nor does it name the method that would have been used to calculate one.

For a percentage outcome, uncertainty depends in part on how many participants were analyzed and how many met the criterion. When estimates come from small groups, the range of plausible values can be broad. That general point is relevant to diagnosis-specific cohorts, but the record does not provide the analyzed denominators or response counts needed to quantify uncertainty for this study.

What can be concluded from a non-randomized cohort design?

In general, random allocation helps balance measured and unmeasured characteristics between treatment groups, on average. Without randomization, differences between groups may reflect who entered each cohort, the diagnosis represented, or other group characteristics rather than a treatment effect. Here, the registry describes non-randomized allocation, no masking, and cohorts organized by diagnosis. It also explicitly says the arms are not a like-for-like control comparison. Cohort-to-cohort contrasts therefore should be treated as descriptive, not as randomized estimates of comparative efficacy.

The registry does not report an adjustment strategy that would address differences between cohorts, and no analysis entries are recorded. It is not possible to determine from this record whether any adjusted comparisons were planned or performed. General statistical adjustment can account for measured covariates under assumptions, but it cannot automatically remove confounding from factors that were not measured or correctly modeled.

What do the planning assumptions mean?

The stated sample-size illustration uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning assumptions, not a description of the trial’s allocation. The study itself was non-randomized and organized into cohorts. The illustration is therefore a hypothetical planning exercise rather than an account of how this trial was designed.

In general, a sample-size calculation asks how many observations a future study would require under assumptions about the effect to detect, variability, significance level, and power. A calculation based on an observed effect can be sensitive to that estimate, especially when the underlying estimate is imprecise. The illustrations are not observed power and do not show that the study was adequately powered. The registry record does not report its own sample-size justification, target enrollment rationale, or power calculation. For time-to-event outcomes, the stated illustration reports a total number of events; for other outcomes, it reports participants per arm. Neither format changes the fact that the calculations are planning illustrations.

What is not specified about the statistical analysis?

The registry describes the endpoint definition and assessment schedule, but does not report the statistical method used to estimate the primary response percentage, handle missing assessments, or calculate uncertainty. It does not report a prespecified comparison, an analysis model, or an interim-analysis plan. Those details should not be inferred from the endpoint label or from the general planning assumptions. The record’s outcome definitions allow the clinical question to be understood, but they do not establish how the final analysis was conducted.

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("Cohort 2: Ewings Sarcoma Secondary Cohort", "Cohort 4: Osteosarcoma", "Cohort 5: Synovial Sarcoma", "Cohort 6: Rhabdomyosarcoma", "Cohort 7a: Alveolar Soft Part Sarcoma", "Cohort 7b: Desmoplastic Small Round Cell Tumors.")
n      <- c(54, 40, 25, 41, 23, 14)
events <- c(6, 1, 1, 2, 0, 0)
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  Cohort 2: Ewings Sarcoma Secondary Cohort  54  6  11.1  4.2  22.6  5.2  22.2  5.3  22.2
ARM  Cohort 4: Osteosarcoma  40  1  2.5  0.1  13.2  0.4  12.9  0.6  12.9
ARM  Cohort 5: Synovial Sarcoma  25  1  4.0  0.1  20.4  0.7  19.5  0.9  19.6
ARM  Cohort 6: Rhabdomyosarcoma  41  2  4.9  0.6  16.5  1.3  16.1  1.5  16.2
ARM  Cohort 7a: Alveolar Soft Part Sarcoma  23  0  0.0  0.0  14.8  0.0  14.3  0.1  14.2
ARM  Cohort 7b: Desmoplastic Small Round Cell Tumors.  14  0  0.0  0.0  23.2  0.0  21.5  0.2  21.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures. The primary endpoint is a combined complete-or-partial-response percentage in Cohorts 2 to 8, while other listed outcomes include response in Cohort 1, progression-free survival at 18 weeks for Cohorts 2 to 8, adverse events in Cohorts 3 to 8, duration of response, time to progression, failure-free survival, and overall survival. Considering several outcomes creates multiple opportunities to observe apparently notable results. In general, multiplicity procedures can limit the chance of false-positive findings across a family of tests, but the registry record does not report whether any multiplicity adjustment was planned or used.

The record contains no analysis entries and does not report numerical primary endpoint results, confidence intervals, or test results. It also does not report whether the outcomes were analyzed according to a prespecified hierarchy, whether analyses were exploratory, or whether interim analyses were conducted. These details are not reported in the registry record, so the evidence cannot be classified as multiplicity-adjusted or interpreted as though one outcome had been selected as the sole confirmatory test.

The primary population description says it included all randomized participants who received at least 1 dose and had at least 1 post-baseline efficacy assessment. However, the study is also labeled non-randomized. This wording is inconsistent with the recorded allocation design, and the record does not clarify the intended analysis population. The registry specifically states that 0 participants were analyzed for Cohort 3 because no efficacy data were collected for that cohort. Other cohort-specific analysis denominators and the handling of missing assessments are not reported.

In general, missing outcome data can affect an estimate if participants without assessments differ from those assessed. The record does not describe imputation, sensitivity analyses, or reasons for missing efficacy assessments beyond the note about Cohort 3. No assumption about how missing values were treated should be made.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0.05% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pleural effusion (14.3%), pyrexia (11.1%), intestinal perforation (11.1%), vomiting (11.1%), respiratory failure (9.1%).

The registry lists serious adverse-event counts by cohort, including counts described as at risk and affected, and it separately lists deaths. For example, the Cohort 1 summary lists 70 at risk for serious adverse events and 11 affected; Cohort 2 lists 54 at risk and 13 affected. These are cohort-level descriptive counts. They should not be read as a comparison with a control group, because allocation was non-randomized and the registry says the arms are not like-for-like comparisons.

Selected serious-event terms are listed with percentages: pleural effusion, 14.3%; pyrexia, 11.1%; intestinal perforation, 11.1%; vomiting, 11.1%; respiratory failure, 9.1%; and constipation, 9.1%. The registry record does not report the denominator, time period, or detailed calculation for these percentages. They therefore should not be treated as risks for an individual participant or compared directly across terms without that context.

Deaths appear as a separate count in the cohort summaries, but the record does not define their relationship to treatment, serious adverse events, or a particular follow-up period. Serious adverse-event counts alone do not establish causation, and no safety comparison against a randomized control is available in this record.

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

The study record establishes that R1507 was evaluated in a Phase II, non-randomized study involving multiple sarcoma cohorts. It specifies the primary response question, the World Health Organization response definitions, the assessment schedule, and the intended treatment schedules. It also records safety summaries and a broader set of outcomes, including measures of disease progression and survival.

Those design and endpoint descriptions do not, by themselves, establish the frequency of response or the precision of any estimate. The registry record does not report the primary endpoint’s numerical result, its denominator, or a confidence interval. It also records no analysis entries. Accordingly, the posted registry information does not support a numerical conclusion about the primary response outcome. This absence should not be interpreted as evidence that no responses occurred; the outcome result is simply not reported in the registry record.

The cohort structure also matters. Participants were not randomized to a control treatment, masking was absent, and the cohorts represented different diagnoses and, for the expanded Ewing’s sarcoma cohort, a different dose schedule. The registry explicitly cautions that arms are not a like-for-like control comparison. Any apparent differences among cohorts cannot be taken as a causal comparison of treatment effects from this design alone.

The listed serious adverse-event counts and selected term percentages offer descriptive safety information, but their interpretation is limited by the lack of a control group and by missing details about denominators and timing for the selected terms. The record does not establish whether a listed event was caused by R1507. It also does not report a detailed analysis of the deaths listed in the cohort summaries.

Thus, the record is useful for understanding the study’s structure, endpoint definitions, and reported safety categories. It does not provide enough outcome detail to quantify the primary response finding, compare treatment with a control, or establish a causal benefit-harm balance. Those conclusions require analyses and reporting not present in the registry record.

14. Why This Trial Matters Statistically

This trial raises a central statistical issue in studies spanning rare and varied diagnoses: a pooled description across several cohorts may not represent a single clinically or statistically uniform population. The study separated participants into diagnosis-specific cohorts, which makes the structure visible, but also limits the meaning of comparisons between those cohorts. Differences in response or safety summaries could reflect the differing diagnoses and participant groups rather than a treatment contrast.

The primary endpoint is a defined response percentage, but a usable estimate requires both a reported response count and an analysis denominator. The registry record gives neither for the primary endpoint. The stated enrollment of 317 cannot substitute for those endpoint-specific quantities. This illustrates why registry enrollment, analysis population, and outcome denominator must be distinguished when reading clinical trial results.

The record also shows why population definitions deserve scrutiny. Its primary population description refers to randomized participants, while the study allocation is labeled non-randomized. Without clarification, the intended analysis population is uncertain. The explicit note that Cohort 3 had no efficacy data and no participants analyzed further demonstrates that enrollment does not guarantee contribution to every outcome.

Finally, the registry’s warning that the arms are not like-for-like control comparisons is essential to interpretation. A non-randomized, open-label study can describe outcomes and safety in treated cohorts, but cohort comparisons do not have the protection against confounding that randomization is intended to provide. The absence of numerical primary results and analysis details makes that distinction especially consequential: the record describes what the study set out to measure, but does not give the reported evidence needed to estimate the endpoint or its uncertainty.

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.

Several limitations are specific to the information recorded for this study. The design is non-randomized and unmasked, and the registry cautions that the arms are not a like-for-like control comparison. The cohorts differ by sarcoma diagnosis, while the expanded Ewing’s sarcoma cohort also has a different dose schedule from the other cohorts. These features limit cross-cohort comparisons and preclude treating them as randomized treatment contrasts.

The primary endpoint is described, but its numerical result, analyzed denominator, and uncertainty interval are not reported in the registry record. The record notes no efficacy data and no participants analyzed for Cohort 3. It gives an enrollment of 317, but that figure does not identify how many participants contributed to any particular endpoint. The analysis-population description refers to randomized participants despite the non-randomized allocation label, and the record does not resolve the discrepancy.

The registry lists 13 outcome measures but no analysis entries. It does not report the statistical analysis plan, multiplicity strategy, missing-data methods, sample-size justification, interim analyses, or detailed methods for the reported safety percentages. The study is marked terminated, but the reason for termination is not reported in the registry record. These omissions constrain interpretation of both the efficacy and safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of R1507 in Participants With Recurrent or Refractory Sarcoma — NCT00642941.
• Registry record last updated 2021-02-03; status last verified 2021-01.
• Results first posted 2021-02-03.
• 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

The registry describes NCT00642941, a Phase II, non-randomized, unmasked, parallel-cohort study of R1507 in participants with recurrent or refractory sarcoma. Hoffmann-La Roche is listed as sponsor. Enrollment is recorded as 317; the study began on 2007-12-18, had a primary completion date of 2014-02-19, and is marked terminated.

The primary endpoint is the percentage with complete or partial response by World Health Organization criteria in Cohorts 2 to 8. The record gives its definition and assessment schedule, but does not report a numerical primary result. It notes that no participants were analyzed for Cohort 3 because efficacy data were not collected. Cohort-level serious adverse-event counts and selected serious-event term percentages are listed, but the record does not provide a randomized control comparison. The termination reason and detailed statistical analysis methods are not reported in the registry record.