Plinabulin vs. Pegfilgrastim in Patients With Solid Tumors Receiving Docetaxel Myelosuppressive Chemotherapy Phase 2: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Plinabulin vs. Pegfilgrastim in Patients With Solid Tumors Receiving Docetaxel Myelosuppressive Chemotherapy Phase 2 (NCT04345900), a randomized phase 2 study. The primary outcome is DSN.

2. Clinical Question

3. Trial Design

This was a randomized, phase 2, multicenter study with a parallel-group design. The registry record lists no masking, so the study was open-label. Enrollment was 55, and the record status is completed. The study start date was 2017-04-05, and primary completion was 2018-03-20.

The four regimens described in the record combine docetaxel at 75 mg/m2 with one of three plinabulin doses—5, 10, or 20 mg/m2—or with pegfilgrastim at 6 mg. The posted primary outcome reports four generic arm labels, with 13 participants in Arm 1 and 14 in each of Arms 2, 3, and 4. The registry record does not explicitly connect each generic outcome label to a named regimen, so the numerical arm comparisons are best read using those generic labels.

The primary outcome concerns duration of severe neutropenia during Cycle 1, which is described as a 21-day cycle. The record says neutrophil counts were to be assessed at baseline and on Days 1, 2, 6, 7, 8, 9, 10, and 15 of Cycle 1. It specifies pre-dose timing on dosing days and equivalent pre-dose timing on other assessment days. The outcomes also include pharmacokinetic measures, blood pressure, and area over the neutropenia curve. Eight secondary outcomes are posted.

The registry record does not report the randomization procedure, allocation concealment, or the original sample-size justification. It also does not describe the intended statistical analysis plan in detail.

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

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 DSN, measured over At the end of Cycle 1 (each cycle is 21 days).

The primary endpoint is duration of Grade 4 neutropenia, abbreviated DSN, measured in days at the end of Cycle 1. Grade 4 neutropenia is defined in the registry record as an absolute neutrophil count below 0.5 × 109/L. The posted summary uses the mean and standard deviation for each arm.

DSN describes how long a participant experiences the most severe defined level of neutropenia during the assessment period. It is therefore a duration measure, rather than a single blood count or a count of episodes. In this study it focuses on Cycle 1, with neutrophil counts scheduled at baseline and at specified points during that cycle. The registry record does not give a more detailed operational rule for determining the start and end of an episode or handling intervals between measurements.

As a continuous endpoint, the arm means provide a concise description of the average duration in each group, while the standard deviations describe participant-to-participant spread. Mean differences compare those group averages. They do not show how every participant fared, and the mean alone does not describe the full distribution or the timing of neutropenia.

Use of this endpoint defines the statistical question as a comparison of average duration during the first cycle. It does not by itself establish the clinical importance of a difference, nor does it answer questions about later cycles or outcomes not included in the endpoint.

7. Results Posted in the Registry

• Arm 2: mean 0.36 versus 0.15 on control; difference 0.21 (95% CI -0.32 to 0.74), standardized effect d = 0.29; z-test p = 0.436.
• Arm 3: mean 0.43 versus 0.15 on control; difference 0.28 (95% CI -0.33 to 0.89), standardized effect d = 0.34; z-test p = 0.365.
• Arm 4: mean 0.29 versus 0.15 on control; difference 0.14 (95% CI -0.24 to 0.52), standardized effect d = 0.27; z-test p = 0.470.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it measures duration in days, and the posted summaries report a mean and standard deviation for each arm. A mean is the arithmetic average across participants with an outcome value. It describes the center of the observed values but can be influenced by unusually high or low observations. A standard deviation describes how dispersed participant values are around that mean; it is not the uncertainty of the mean itself.

What does the mean difference represent?

Each posted comparison expresses the difference between the mean in a comparison arm and the mean in the control arm. A positive estimate means the comparison-arm mean is higher than the control mean in the posted calculation. The estimate is a contrast between group averages, not a count of participants affected and not a description of each participant’s individual change. The registry record labels the endpoint mean and reports unadjusted mean differences for the three non-control arms.

These are unadjusted comparisons based on the posted group summaries. An adjusted analysis could account for other variables or a prespecified model, but the registry record does not report such an analysis. The posted results should therefore be read as the comparisons actually described, without attributing covariate adjustment or other modeling choices to them.

How should the confidence intervals be read?

A confidence interval expresses uncertainty around an estimated mean difference under the statistical method used. It gives a range of values compatible with the observed data and that method, rather than a guarantee that the true value lies within the particular interval. When an interval spans zero, the data are compatible with a zero mean difference as well as with differences on either side of zero. A wide interval signals limited precision: a broad range of effects remains compatible with the estimate.

The intervals posted for all three comparisons cross zero. The point estimates are positive, but the intervals do not rule out a negative difference or a larger positive difference. This combination is why the estimates should be interpreted together with their uncertainty, not as definitive evidence based solely on the direction of the means.

What role do p-values play?

The posted p-values are unadjusted. A p-value summarizes how unusual data at least as discrepant as those observed would be under a specified null hypothesis and the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The registry record does not report the test details or a multiplicity strategy, so the p-values should not be interpreted as adjusted for the several arm comparisons.

There are three comparisons with the control arm. When several comparisons are considered, the chance of at least one apparently notable result can be affected by multiplicity. Whether and how the study addressed that issue is not reported in the registry record. This is relevant when reading individual unadjusted p-values, but it does not change the reported point estimates or intervals.

What do the pooled standard deviations and standardized effects describe?

The comparison summaries include a pooled standard deviation and a standardized effect size. A pooled standard deviation combines the within-arm variability for a two-group contrast under a common-variability approach. A standardized effect expresses the mean difference relative to that variability, making the contrast unitless. These are statistical summaries of the posted data; they do not replace the original mean difference in days, and they do not establish clinical importance. The registry record does not state that the trial was designed or powered around these standardized effects.

Why does sample size affect precision?

With a continuous outcome, the precision of a group mean and the difference between means depends on the amount of variability and the number of observations. Small groups can leave considerable uncertainty, particularly when participant outcomes vary. Here, each arm has 13 or 14 participants. The confidence intervals reflect the uncertainty in the posted comparisons; they should not be read as evidence that the estimated differences are exact or stable.

The sample-size calculations are planning illustrations based on observed effects and stated assumptions, not the study’s documented original design. They use a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect set to a stated fraction of the observed effect. The number of participants required rises when planning to detect a smaller effect. The original design assumptions are not reported in the registry record.

Finally, the available summaries do not reveal the distribution of individual DSN values, the presence of influential observations, or how missing measurements were treated. Nor do they provide a detailed sponsor analysis plan. Those details can affect interpretation, but cannot be reconstructed from the arm means and standard deviations alone.

10. Confidence Intervals and Precision

All three posted confidence intervals for the mean difference are broad and include zero. Arm 2 versus Arm 1 has an estimate of 0.21 days and a confidence interval from -0.318 to 0.738. Arm 3 versus Arm 1 has an estimate of 0.28 days and a confidence interval from -0.326 to 0.886. Arm 4 versus Arm 1 has an estimate of 0.14 days and a confidence interval from -0.240 to 0.520.

Because each interval spans values below and above zero, the estimates do not precisely distinguish a positive mean difference from no difference or a negative mean difference. Their widths also mean that effects meaningfully larger than the point estimates remain compatible with the data. The results are therefore uncertain, not evidence that the arms have identical mean DSN.

Each comparison uses small groups: Arm 1 includes 13 participants, and each comparison arm includes 14. The observed standard deviations range from 0.376 days in Arm 1 to 1.089 days in Arm 3. Variation among participant outcomes, together with the limited group sizes, is reflected in the uncertainty of the mean differences.

A confidence interval describes statistical precision under the method used; it does not resolve questions about study conduct, missing measurements, analysis populations, or clinical importance. The registry record does not report detailed analysis methods for the sponsor’s comparisons. These intervals are the posted comparisons and should be interpreted as unadjusted estimates, not as a complete account of every possible source of uncertainty.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size displays are planning illustrations, not a report of the trial’s original design justification. The listed figures are participants per arm, not total participants across both arms and not total events. The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They use an effect to detect equal to the stated fraction of the observed effect. The trial’s own original design assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm under those assumptions for an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column gives the corresponding number per arm for a 90% chance. Power is a property of a proposed design under an assumed effect and statistical model; it is not a measure of whether the observed result is true.

Rows planning for 100%, 75%, and 50% of an observed effect represent different effect sizes to detect. Smaller effects require more participants to detect under the same assumptions, which is why the required counts increase as the assumed fraction becomes smaller. The values differ across comparisons because their observed effects and variability differ. These figures are not observed power.

The illustrations use two-arm comparisons. They should not be read as a single enrollment target for the full four-arm trial, or as evidence about the study’s actual planned enrollment. They describe hypothetical requirements under the stated calculation assumptions only.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.210; pooled standard deviation σ = 0.719.
2. n = 2 × (1.96 + 0.842)² × 0.719² / 0.210² = 183.9, rounded up to 184 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.21                      # observed difference in means
sigma <- 0.718777990759316                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4345900)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 184 (80% power), 247 (90% power)
 75% of observed effect: n per arm = 327 (80% power), 438 (90% power)
 50% of observed effect: n per arm = 736 (80% power), 985 (90% power)
power.t.test: 184.9 
Simulated power at n = 184 per arm: 0.795 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The posted primary outcome contains three comparisons against Arm 1, and the record lists eight secondary outcomes. The registry record does not report a prespecified strategy for controlling multiplicity across the comparisons or outcomes. The displayed comparison p-values are unadjusted, so they should not be treated as accounting for the possibility of multiple testing.

The record lists no analysis records, although it does post arm-level primary outcome summaries and unadjusted comparisons. It does not report the statistical analysis plan, the intended primary analysis model, or whether any additional analyses were conducted. The test details underlying the posted comparisons are also not described. In particular, it is not reported whether analyses were adjusted for baseline characteristics, site, or other variables.

The primary outcome population is not specified in the posted record. It does not say whether the summaries include all randomized participants, only participants who received treatment, or a different analysis population. The record also does not report the number of participants with missing DSN data, the reasons for missingness, or any imputation or other missing-data procedure.

These gaps matter because analysis populations, missing-data handling, and multiplicity choices can affect the interpretation of estimates and inferential results. They do not justify assuming that a particular method was used. The posted means, standard deviations, confidence intervals, and unadjusted p-values can be described as reported, but the registry record does not provide enough information to establish how they relate to a complete prespecified analysis strategy.

14. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (7.7%), respiratory failure (7.7%), febrile neutropenia (7.1%), vomitting (7.1%), asthenia (7.1%).

For serious adverse events, the registry record reports 2 affected participants in each arm. The numbers at risk were 13 in Arm 1 and 14 in each of Arms 2, 3, and 4. The record also reports 1 death in each arm. These are counts as posted; they should be read alongside the different numbers at risk in the arms.

The serious-event terms listed include Atrial Fibrillation at 7.7%, Respiratory Failure at 7.7%, Febrile Neutropenia at 7.1%, Vomitting at 7.1%, Asthenia at 7.1%, and Disease Progression at 7.1%. The registry record lists these terms and percentages without specifying their arm-level distribution in the information. They should not be assigned to a particular arm based on the aggregate listing.

The counts and terms describe what is posted in the registry record. They do not establish comparative safety, causation, or the likelihood of an event outside this study. The record does not provide additional detail on event timing, severity beyond the serious-event classification, or attribution.

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

The posted Cycle 1 DSN means were 0.15 days in Arm 1, 0.36 days in Arm 2, 0.43 days in Arm 3, and 0.29 days in Arm 4. The mean differences versus Arm 1 were 0.21, 0.28, and 0.14 days for Arms 2, 3, and 4, respectively. Each corresponding confidence interval includes zero and extends in both directions. The posted data therefore leave substantial uncertainty about the direction and size of the underlying mean differences.

These results describe the observed group summaries and unadjusted contrasts for one continuous endpoint during Cycle 1. They do not establish that the groups are identical, nor do the positive point estimates alone establish a reliable difference. The small arm sizes and variability in DSN are relevant to the breadth of the confidence intervals.

The results do not by themselves establish the effect of a particular named regimen because the registry outcome display uses generic arm labels and does not explicitly map those labels to the regimen descriptions. They also do not answer questions about outcomes beyond the posted endpoint, subsequent cycles, or differences in the wider population of patients with solid tumors.

Clinical importance cannot be determined from the mean differences alone. The registry record does not report a threshold for a clinically important DSN difference or additional context needed to interpret such a threshold. Nor does the posted statistical evidence establish a treatment recommendation. It is a record of observed results with considerable uncertainty, not a substitute for broader evaluation of the trial’s outcomes and limitations.

16. Why This Trial Matters Statistically

This trial illustrates how a randomized comparison can produce clear-looking numerical differences in group means while leaving substantial uncertainty about the underlying contrast. The observed means vary across the four arms, but the confidence intervals for all three comparisons with the control include zero and extend across both negative and positive values. Statistical interpretation therefore depends on the estimates and their precision together, not on the ordering of the means alone.

The group sizes are small, and the standard deviations differ across arms. Those features are important when interpreting continuous outcomes: an average can conceal variation among participants, and limited data can leave a wide range of plausible mean differences. Reporting intervals helps make that uncertainty visible rather than presenting a point estimate as if it were definitive.

The trial also highlights the value of clear registry reporting. Generic outcome arm labels are not explicitly connected to the named regimens in the posted outcomes, and the registry record does not describe the full analysis plan, population definitions, missing-data handling, or multiplicity strategy. These omissions limit how confidently readers can connect the numerical comparisons to specific regimens or assess the inferential framework.

Finally, planning calculations based on an observed effect are not the same as the study’s original design justification. Their assumptions should be read as hypothetical inputs for interpreting illustrative participant requirements, rather than as evidence about what the trial was designed to detect. Together, these points show why effect estimates, uncertainty, reporting detail, and design context all matter in a statistical reading of a clinical trial.

17. 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 reports an enrollment of 55, with 13 participants in Arm 1 and 14 in each other arm for the primary outcome. These small groups limit precision, as reflected in the broad confidence intervals. The standard deviations also indicate variability in the observed endpoint values.

The outcome arms are labeled generically, and the record does not explicitly link each arm label to a named regimen in the posted outcome results. This restricts interpretation of the numerical comparisons by treatment name. The record describes the trial as randomized, but the randomization method and allocation concealment are not reported. The study was unmasked.

The endpoint is limited to duration of Grade 4 neutropenia during Cycle 1. The record does not provide detailed rules for calculating duration between scheduled blood-count assessments. It also does not report the primary analysis population, the amount or handling of missing outcome data, or a full statistical analysis plan. Multiplicity handling for the several comparisons and outcomes is not reported.

The registry record does not give the original sample-size justification, so the illustrative calculations based on observed effects cannot clarify the design rationale. The posted primary comparisons are unadjusted, and the record does not describe additional sponsor analyses. These limitations do not erase the posted findings, but they constrain how precisely and broadly those findings can be interpreted.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Plinabulin vs. Pegfilgrastim in Patients With Solid Tumors Receiving Docetaxel Myelosuppressive Chemotherapy Phase 2 — NCT04345900.
• Registry record last updated 2024-05-16; status last verified 2024-03.
• Results first posted 2024-05-16.
• 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.

21. Record Summary

NCT04345900 is a completed randomized, open-label, parallel-group phase 2 study of docetaxel-based regimens in patients with solid tumors. The registry record describes docetaxel with plinabulin at 5, 10, or 20 mg/m2, or with pegfilgrastim at 6 mg. Enrollment was 55.

The primary outcome was mean duration of Grade 4 neutropenia in days at the end of Cycle 1. Posted means ranged from 0.15 days in Arm 1 to 0.43 days in Arm 3. All three unadjusted comparisons with Arm 1 had confidence intervals that included zero. The record does not explicitly map the generic outcome arm labels to the named regimens and does not report important details of the analysis population, missing-data handling, or multiplicity strategy.