Study of Dalantercept in Patients With Squamous Cell Carcinoma of the Head and Neck: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Dalantercept in Patients With Squamous Cell Carcinoma of the Head and Neck (NCT01458392), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

The study concerns whether tumor assessments recorded complete or partial response during dalantercept treatment, rather than a comparison of dalantercept with another treatment or with no treatment. The endpoint definition describes complete response as disappearance of all target lesions and partial response as at least a 30% decrease in the sum of the longest diameters of target lesions. Assessment was by MRI for target lesions.

The efficacy description distinguishes the people enrolled from those included in the response assessment. It says that the two patients in the 80 mg fixed-dose group were excluded from efficacy analysis after the protocol was amended to use weight-based dosing for the remainder of the study population. It also says that 40 patients received at least one dose in either weight-based group, but the eligibility statement in the registry record is incomplete. The number actually evaluable for ORR is not reported in the registry record.

Accordingly, the clinical question can be described from the intended endpoint and population, but the result cannot be characterized from the posted registry information. A response proportion, confidence interval, or conclusion about the observed tumor responses is not reported in the registry record.

3. Trial Design

This was an open-label Phase 2 study of dalantercept in patients with recurrent or metastatic SCCHN. Its recorded model is single-group. The registry lists no allocation scheme and no masking. Enrollment was 46, and the study status is completed. The recorded start was 2011-10 and primary completion was 2015-06.

The intervention was dalantercept. The registry identifies three dose groups: Dalantercept 80 mg, Dalantercept 0.6 mg/kg, and Dalantercept 1.2 mg/kg. The efficacy description says the two patients at the fixed-dose level were excluded from efficacy analysis because the protocol had been amended to incorporate weight-based dosing for the remainder of the study population. It reports that 40 received at least one dose in the two weight-based groups, but its description of the efficacy population ends before completing the eligibility criteria. A full account of the analysis population is therefore not reported in the registry record.

With no control group, the study does not provide a randomized comparison between dalantercept and another intervention. Nor should the different dose groups be treated as exchangeable treatment arms: the registry record does not describe random assignment, and the dose groups arose in the context of a protocol amendment. Differences between groups could not, from this design alone, be attributed solely to dose.

The primary endpoint was ORR, defined using RECIST version 1.1. Tumor assessments were planned every 6 weeks, up to 30 days after the last dose and/or disease progression, for up to approximately 2 years. Listed secondary outcomes included safety and tolerability, serum concentration after single and multiple doses, progression-free survival, overall survival, and disease control rate. The registry lists 7 outcome measures, but detailed results for those outcomes are not reported in the registry record.

The sponsor is Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA. The registry record does not report a detailed statistical analysis plan, a sample-size justification, or the rationale for the enrolled number.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The two patients at the 80 mg, fixed-dose level were excluded from the efficacy analysis as the protocol had been amended to incorporate weight-based dosing for the remainder of the study population. 40 received at least one dose of study drug in either the 0.6 mg/kg or 1.2 mg/kg dose groups and had at least one on-treatment tumor assessment.

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 Objective Response Rate (ORR), measured over Tumor assessments performed every 6 weeks, up to 30 days after the last dose of dalantercept and/or disease progression, up to approximately 2 years..

ORR measures the proportion of evaluable patients whose best recorded tumor response met the criteria for complete response or partial response. In this study, RECIST version 1.1 was used to evaluate efficacy. Complete response meant disappearance of all target lesions. Partial response meant at least a 30% decrease in the sum of the longest diameters of target lesions. Target lesions were assessed by MRI.

The endpoint is used in tumor studies to describe the frequency of observed tumor shrinkage meeting prespecified response criteria. It reduces each evaluable patient's assessment to a response category and then reports the share meeting either response criterion. The registry definition specifies that patients needed a measurable lesion at baseline and a post-baseline disease assessment to be evaluable; patients with clinical or radiological progression before their scheduled assessment were also considered evaluable.

Those criteria are important to interpretation: ORR is not the same as time to progression, duration of response, or overall survival. The registry lists progression-free survival, overall survival, and disease control rate as secondary outcomes, but their results are not reported in the registry record.

The registry identifies ORR as the primary endpoint and gives a 95% confidence interval as its dispersion measure. However, it does not report the number of responses, the number evaluable, the estimated response rate, or the interval bounds. The endpoint's definition is available, but its observed result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each evaluable patient either met the complete- or partial-response criteria or did not. The registry describes the result as a proportion and names a 95% confidence interval as its measure of dispersion. The observed count and proportion are not reported in the registry record, so no numerical interpretation of the endpoint is possible.

What does a response proportion represent?

General explanation: a proportion combines a numerator—the number of people meeting a defined outcome—with a denominator—the number of people assessed for that outcome. The denominator matters because it determines which participants contribute to the estimate. For this trial, the registry specifies evaluability criteria, but it does not report the number meeting those criteria or the number who responded. It would be inappropriate to substitute enrollment or the number who received a dose for the missing endpoint denominator.

The stated response criteria are based on tumor measurements under RECIST version 1.1. Complete response is disappearance of all target lesions; partial response is at least a 30% decrease in the sum of the longest diameters of target lesions. The registry says target lesions were assessed by MRI. These criteria define how observations are categorized; they do not, by themselves, reveal how many participants met either category.

How should a confidence interval be read?

General explanation: a confidence interval expresses uncertainty around an estimate under a statistical procedure and its assumptions. For a response proportion, the interval would indicate a range of values compatible with the observed data under that procedure. It is not a guarantee that a particular value is true, and it does not resolve design limitations such as the lack of a control group. The registry names a 95% confidence interval but does not report its bounds or the method used to calculate it. Its precision therefore cannot be evaluated.

For a single-group estimate, the interval would describe uncertainty in the response proportion for the analyzed population. It would not convert the observed rate into a comparison with an untreated group or another therapy. That distinction is especially important in an open-label, single-group study, where there is no concurrent randomized comparator in the registry design.

What can the dose groups tell us?

The registry lists a fixed 80 mg group and two weight-based groups, 0.6 mg/kg and 1.2 mg/kg. The efficacy description says the two fixed-dose patients were excluded from efficacy analysis because the protocol was amended to use weight-based dosing for the remainder of the study population. This amendment and exclusion affect which group is relevant to the described efficacy analysis. The record does not report a randomized dose assignment or establish that the groups can be directly compared. A difference between group outcomes, even if reported elsewhere, would not automatically identify a dose effect.

The registry lists no statistical analyses. It does not report a model, adjustment variables, an inferential test, handling of repeated assessments, or a rule for choosing among response assessments. These details should not be inferred from the endpoint definition alone.

What do planning calculations mean?

General explanation: sample-size planning asks how many observations might be needed under stated assumptions to detect a specified effect with a chosen statistical procedure. The planning assumptions associated with the posted illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is stated as a fraction of the observed effect. For time-to-event outcomes, the illustrations concern total events, while other outcomes are expressed as participants per arm. These assumptions describe planning illustrations, not the design of this single-group study.

Such planning values are not observed power and do not show that a trial had a particular chance of detecting its result. They depend on the assumptions used, including the effect used as a reference. The registry record does not report its own sample-size justification, and no conclusion about the adequacy of the planned enrollment can be drawn from the information available.

General explanation: over-dispersion matters when the variability in data is greater than a statistical model assumes, because standard errors can then be understated and intervals too narrow. That issue is relevant to some count-data models, but the primary endpoint is described as a binary response proportion, and the registry does not report a model requiring an over-dispersion assessment. No claim about over-dispersion or a model choice can be made for this trial.

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("Dalantercept 0.6 mg/kg", "Dalantercept 1.2 mg/kg")
n      <- c(13, 27)
events <- c(0, 2)
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  Dalantercept 0.6 mg/kg  13  0  0.0  0.0  24.7  0.0  22.8  0.2  23.2
ARM  Dalantercept 1.2 mg/kg  27  2  7.4  0.9  24.3  2.1  23.4  2.3  23.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists ORR as the primary outcome and lists secondary outcomes covering safety and tolerability, dalantercept serum concentration after single and multiple doses, progression-free survival, overall survival, and disease control rate. It records 7 outcome measures. The results for these listed outcomes are not reported in the registry record.

Multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined. General explanation: without a prespecified hierarchy or adjustment strategy, interpreting multiple tests can raise the chance that at least one apparently notable finding occurs by chance. The registry record does not report an outcome hierarchy, multiplicity adjustment, planned subgroup analyses, or a complete statistical analysis plan. It is therefore not possible to determine how the study intended to manage multiplicity.

Missing-data handling is also not reported in the registry record. The ORR definition states that evaluability required a measurable baseline lesion and at least one disease assessment after baseline; it also says progression before a scheduled assessment counted toward evaluability. The record does not give the number of patients excluded for lack of an assessment, describe how other missing tumor assessments were handled, or state whether any imputation or sensitivity analysis was used.

The efficacy population description is incomplete: it states that two patients in the 80 mg group were excluded and that 40 received at least one dose in the weight-based groups, but does not finish describing the latter population. The number evaluable for response and the relationship between treated and analyzed participants are therefore not fully documented. These omissions limit assessment of selection into the endpoint analysis and of how robust the result would be to alternative missing-data assumptions.

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: tongue cancer metastatic (50.0%), pleural effusion (7.7%), aspiration (7.7%), respiratory distress (7.7%), disease progression (7.7%).

The registry reports serious adverse-event counts by dose group. For Dalantercept 80 mg, 1 of 2 participants at risk was affected; for Dalantercept 0.6 mg/kg, 6 of 13 were affected; and for Dalantercept 1.2 mg/kg, 6 of 31 were affected. These are group counts, not a randomized comparison. The registry also reports other adverse events affecting 2 of 2, 13 of 13, and 31 of 31 participants in those respective groups.

The listed serious-event terms include Tongue cancer metastatic at 50.0%, and Pleural effusion, Aspiration, Respiratory distress, Disease progression, and Metastases to central nervous system, each at 7.7%. These percentages are registry entries; the record does not provide enough detail in this summary to reconstruct how each term's denominator was defined or how overlapping events were handled. A participant may experience more than one event, so terms should not be treated as mutually exclusive categories without further information.

The groups differ in size, and the fixed-dose group had only 2 participants at risk. Counts and percentages from small groups are imprecise, and the groups should not be read as a controlled dose comparison. Death counts are not reported in the registry record. These figures describe reported safety events; they do not establish that dalantercept caused any particular event.

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

The registry record establishes the study's purpose and design: it was an open-label, Phase 2, single-group study of dalantercept in recurrent or metastatic SCCHN, with ORR as the primary endpoint. It also supplies the response criteria, the intended assessment schedule, dose groups, and some safety counts. Those details clarify what the trial set out to measure.

The record does not report the observed ORR, its numerator or denominator, or the 95% confidence interval. It therefore cannot support a statement about the frequency or precision of objective responses in the analyzed population. The registry also does not report results for the listed secondary outcomes, including progression-free survival, overall survival, or disease control rate. Their inclusion as outcomes should not be confused with evidence that results were observed or reported.

Even if a response estimate were available, the single-group design would answer a descriptive question about outcomes among assessed participants, not a randomized question about how outcomes compare with a control. There is no separate comparator in the registry record. The dose groups do not supply a randomized control comparison, and the fixed-dose group was excluded from efficacy analysis after the protocol amendment described in the record.

The safety counts are also descriptive. They give the number of participants affected in each listed group, but do not provide a controlled contrast, exposure-adjusted rates, or a causal assessment. The serious-event terms should be read as reported categories, not as proof that the intervention caused those events.

General explanation: statistical uncertainty and causal uncertainty are different. A confidence interval can describe sampling uncertainty around an estimate, while a comparative design helps address whether differences in outcomes are attributable to an intervention rather than other factors. The registry does not provide the primary interval, and the single-group design lacks a concurrent randomized comparator. The available record therefore supports a description of the planned question and reported safety counts, but not a conclusion about comparative benefit or harm.

14. Why This Trial Matters Statistically

This trial illustrates why endpoint definitions and analysis populations matter as much as the name of an outcome. ORR has a specific RECIST-based definition, and the registry describes who could be considered evaluable. Yet without the response count, evaluable denominator, and confidence interval, the primary result cannot be interpreted. A clearly defined endpoint is necessary for analysis, but it is not a substitute for reporting the result.

The registry also documents a change from a fixed-dose group to weight-based dosing, along with exclusion of the two fixed-dose patients from efficacy analysis. This makes the boundary between enrollment, treatment exposure, and the efficacy population especially important. When a registry description of that population is incomplete, readers cannot fully reconstruct who contributed to the primary endpoint.

Design is another central statistical issue. A single-group study can describe outcomes among participants receiving the intervention, but it does not create a randomized comparison. The listed dose groups do not act as a control group, particularly given the amendment and the absence of recorded random allocation. Keeping descriptive findings separate from comparative claims is essential to accurate interpretation.

Finally, safety summaries need denominators and context. The record gives counts by dose group and lists serious-event terms, but group sizes differ and no control group is available. Those figures can inform a description of what was recorded, while leaving causal attribution and controlled comparisons unresolved. The registry's missing primary result and limited analysis details demonstrate why transparent reporting of estimates, uncertainty, analysis populations, and missing-data handling is important for statistical interpretation.

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 most consequential limitation of the available registry record is that the primary endpoint result is not reported. The ORR estimate, response count, evaluable denominator, and 95% confidence interval are all absent. Without them, readers cannot judge either the observed response frequency or its statistical precision.

The record describes the efficacy population incompletely. It states that the two patients treated at 80 mg were excluded from efficacy analysis after the protocol changed to weight-based dosing, and that 40 received at least one dose in the 0.6 mg/kg or 1.2 mg/kg groups. The remainder of the eligibility statement is unfinished, and the final number evaluable for ORR is not reported. The registry does not explain missing tumor assessments or report sensitivity analyses.

The single-group design has no randomized control arm. The dose groups are not a like-for-like control comparison, and the record does not describe random assignment. The open-label design also means masking was absent. The registry does not report a detailed statistical analysis plan, sample-size justification, planned interim analyses, or multiplicity strategy.

Safety reporting is limited to group counts and selected serious-event terms in this record. Death counts are not reported, and detailed event timing, exposure-adjusted rates, and causal assessments are not posted in the registry record. The secondary outcomes are listed, but their results are not reported. These gaps restrict both efficacy interpretation and assessment of the completeness of the reported analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Dalantercept in Patients With Squamous Cell Carcinoma of the Head and Neck — NCT01458392.
• Registry record last updated 2022-10-05; status last verified 2022-09.
• Results first posted 2017-06-27.
• 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 record describes NCT01458392, an open-label Phase 2 study of dalantercept in recurrent or metastatic SCCHN. It is recorded as completed, with enrollment of 46, a single-group model, no masking, and allocation listed as NA. The recorded start was 2011-10 and primary completion was 2015-06.

ORR by RECIST version 1.1 was the primary endpoint. The record describes an 80 mg fixed-dose group and weight-based groups of 0.6 mg/kg and 1.2 mg/kg; the two fixed-dose patients were excluded from efficacy analysis after a protocol amendment. The primary response estimate and confidence interval are not reported in the registry record. Listed secondary outcomes include safety and tolerability, serum concentration, progression-free survival, overall survival, and disease control rate.

Safety counts and selected serious-event terms are recorded by dose group. The registry does not report a detailed statistical analysis plan, sample-size justification, or the primary endpoint result.