MSC2015103B in Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MSC2015103B in Solid Tumors (NCT01453387), a non-randomized phase 1 study. The primary outcome is Number of Subjects Who Experienced Dose-limiting Toxicities (DLT).

2. Clinical Question

The trial asked whether the experimental drug MSC2015103B could be administered to people with advanced solid tumors at different dose levels using either of two treatment schedules, with attention to safety, tolerability, and how the body handles the drug. The registry describes Schedule 1 as once daily on one day per week over a 21-day period, and Schedule 2 as once daily three times per week over a 21-day period. It also states that the investigators sought to explore possible anti-cancer effects.

This is an early-phase, safety-focused question rather than a confirmatory comparison of treatment effectiveness. The listed secondary outcomes include treatment-emergent adverse events, clinically significant laboratory abnormalities, and pharmacokinetic measures such as maximum plasma concentration, time to maximum concentration, half-life, and area under the concentration curve. The registry record does not report results for those pharmacokinetic measures or an anti-cancer efficacy result. Consequently, the central interpretation is limited to the stated aims, design, and posted safety counts; it cannot establish whether the schedules differ in safety or whether the drug has anti-cancer activity.

3. Trial Design

This was a Phase I, first-in-human, dose-escalation study of oral MSC2015103B in advanced solid tumors. The registry lists a non-randomized allocation, no masking, and a parallel model. It reports enrollment of 28 and identifies two groups: Part 1 - MSC2015103B (Schedule 1) and Part 1 - MSC2015103B (Schedule 2). The groups are described as separate schedule groups, not as randomized treatment arms with a control condition.

The brief summary says the study examined different dose levels and two ways of arranging treatment within a 21-day period. Schedule 1 is described as once daily on one day per week, and Schedule 2 as once daily three times per week. The arm descriptions do not give further detail, and the exact dose levels, escalation steps, and rules for moving between dose levels are not reported in the registry record.

The primary endpoint was the number of subjects who experienced dose-limiting toxicities through Day 21 of Cycle 1. The safety analysis set included subjects who received at least one administration of the trial medication. The registry lists additional outcomes covering treatment-emergent adverse events, related laboratory abnormalities, and pharmacokinetic measures. It reports 15 outcome measures, but does not provide results for all of them in the registry record recorded.

The study start is listed as 2011-09 and primary completion as 2013-07. Its status is terminated. The reason for termination and whether termination affected enrollment, follow-up, or analysis are not reported in the registry record. The registry does not report the planned sample-size rationale, a protocol-level statistical analysis plan, or the detailed dose-escalation design. Because assignment was not randomized, differences between schedule groups should not be interpreted as causal schedule effects. Group comparisons may reflect differences in participants, dose levels, exposure, follow-up, or other factors that the registry record does not describe.

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: Enrolled: 28 subjects were screened for eligibility and all were randomized in to the trial.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Safety analysis set included all the subjects who received at least one administration of the trial medication.

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.

Population: Safety analysis set included all subjects who received at least one administration of the trial medication.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects Who Experienced Dose-limiting Toxicities (DLT), measured over Up to Day 21 of Cycle 1.

The primary endpoint counts subjects who experienced a dose-limiting toxicity, or DLT, through Day 21 of Cycle 1. It is a safety and tolerability measure: it identifies qualifying toxicities during an early, specified treatment period, which is relevant in a dose-escalation study evaluating a drug for the first time in people. The registry states that DLT was evaluated using NCI Common Terminology Criteria for Adverse Events version 4.0.

The registry definition includes qualifying severe non-hematological toxicities, specified blood-related toxicities, serious or life-threatening adverse events, events or abnormalities that impair normal daily physiological functions, and treatment delays of 2 weeks or more due to adverse effects. It also lists exclusions for certain Grade 3 events under stated circumstances and excludes events judged by the investigator to be related to progressive disease. These criteria make the endpoint narrower than a count of every adverse event: an event must meet the stated criteria and fall within the defined period.

Counting affected subjects is a direct way to describe how many people met the DLT definition, but a count alone does not capture the full clinical detail, duration, severity, or timing of each event. The registry record does not report the primary DLT count, so the observed frequency cannot be described from this record. It also does not provide a group-specific DLT result or a statistical comparison for the primary endpoint. The endpoint definition is reported; its result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation begins with the question the endpoint was designed to answer. The primary outcome is a count of subjects meeting a prespecified clinical definition of DLT during a specified period. This differs from a continuous measure, such as a concentration in blood, and from a time-to-event measure, such as time until an event. For a count of affected subjects, a useful descriptive result would ordinarily include the number meeting the definition and the number assessed. The registry record states the endpoint and safety population, but the DLT result is not reported in the registry record.

What does a non-randomized design imply?

Random assignment is one way to balance, on average, measured and unmeasured participant characteristics between groups. This trial is listed as non-randomized, and the two groups represent different schedules. Without randomization, any difference in observed outcomes could be related to the schedule, but could also be related to differences between the people enrolled, the doses received, exposure, or other factors. The registry record does not report enough detail to assess these possibilities. As a result, a simple contrast between the group counts would be descriptive rather than evidence of a causal schedule effect.

The registry also lists no masking. Masking can reduce the influence of knowledge of treatment assignment on some assessments or reporting, depending on the outcome. For safety events, clinical evaluation and investigator attribution may involve judgment. The record describes investigator judgment in the DLT definition and in judging whether laboratory abnormalities were related to trial medication. It does not report procedures intended to mask those judgments.

Why distinguish counts from rates?

A count tells how many subjects experienced an event. A rate or proportion places that count in relation to a defined population at risk or assessed. The serious-event data identify both affected subjects and subjects at risk for each schedule group. Those figures are descriptive of the groups recorded, but the non-randomized design prevents treating them as a randomized comparison. Follow-up duration and exposure can also affect the opportunity to observe adverse events; group-specific follow-up and exposure are not reported in the registry record. General statistical interpretation therefore considers the event counts alongside the population definition, duration, and design rather than reading the counts in isolation.

For outcomes that are uncommon, small group sizes may lead to considerable uncertainty in estimated proportions. This is a general statistical point, not a calculated uncertainty estimate for this study. The registry does not report confidence intervals for the serious-event counts or the primary outcome. No interval should be inferred from the counts alone in the absence of a stated analysis.

What can pharmacokinetic outcomes tell us?

Pharmacokinetic measures describe how drug concentration changes over time in the body. Maximum plasma concentration is the highest measured concentration under the measurement schedule; time to maximum concentration describes when that maximum is reached; terminal half-life characterizes the decline in the terminal phase; and area under a concentration-time curve summarizes exposure over a stated interval. These are general definitions. The registry lists Cmax, Tmax, T1/2, AUC[0-inf], and AUC0-tau as secondary outcomes, but the corresponding numerical results are not reported in the registry record. Definitions of measures do not substitute for observed estimates.

Over-dispersion is a general issue in count data: variability may exceed what a simple model assumes, potentially making conventional uncertainty estimates too narrow. It can matter when modeling counts with substantial heterogeneity. The primary endpoint is described as a subject count, but the registry record does not report a statistical model for it or an analysis that would permit evaluating over-dispersion. It would be inappropriate to claim that any particular model was used.

What does the sample-size information establish?

The registry entries describe sample-size illustrations as planning calculations based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. They also distinguish participant-per-arm illustrations from total-event illustrations for time-to-event settings. These are planning assumptions, not proof that the trial was designed with those assumptions, and not observed power. No sample-size illustration results or trial-specific sample-size justification are reported in the registry record. In particular, the illustration assumptions cannot establish the rationale for enrolling 28 in this non-randomized Phase I study.

The registry reports zero analyses. That means inferential analysis results are not available in the record details; it does not show that investigators performed no analyses outside the registry. Statistical plans, interim analyses, handling of missing outcomes, and any adjustment for multiple testing are not reported in the registry record. Accordingly, interpretation should stay with the reported design and descriptive outcomes, and avoid reconstructing an analysis plan that the record does not describe.

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("Part 1 - MSC2015103B (Schedule 1)", "Part 1 - MSC2015103B (Schedule 2)")
n      <- c(21, 7)
events <- c(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  Part 1 - MSC2015103B (Schedule 1)  21  0  0.0  0.0  16.1  -0.0  15.5  0.1  15.4
ARM  Part 1 - MSC2015103B (Schedule 2)  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary DLT outcome and multiple secondary outcomes, including adverse events, laboratory abnormalities, and pharmacokinetic measures. When a study examines multiple outcomes or makes multiple comparisons, the chance of at least one apparently unusual result can increase. Statistical methods may address this through a prespecified hierarchy or adjustment, but the registry record does not report a multiplicity strategy. No inferential analyses are listed, so there are no reported adjusted or unadjusted tests to interpret.

Missing-data methods are also not reported in the registry record. The record identifies the safety analysis set as subjects who received at least one administration of trial medication, but does not explain how missing assessments, incomplete follow-up, withdrawal, or unavailable pharmacokinetic samples were handled. The number of subjects assessed for the primary endpoint is not reported in the registry record. Enrollment of 28 does not by itself establish how many had evaluable DLT assessments.

The DLT definition includes the period through Day 21 of Cycle 1. The record does not explain how incomplete exposure during that period was handled, or whether participants without a qualifying event but with incomplete observation were treated differently from participants completing the assessment period. The registry status is terminated, but the reason and consequences for outcome availability are not reported. These omissions limit assessment of completeness and potential bias. They do not justify assuming that missing outcomes were either absent or present.

The registry does not report a statistical analysis plan, planned subgroup analyses, interim analyses, or a strategy for controlling false-positive findings. Those methods are not reported in the registry record. Results should therefore be read as descriptive registry information, not as evidence that a particular multiplicity or missing-data procedure was applied.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nausea (14.3%), vomiting (14.3%), pneumonia (14.3%), catheter site infection (14.3%), feeding tube complication (14.3%).

The serious adverse event data are grouped by treatment schedule. For Schedule 1, the registry reports 21 subjects at risk and 4 affected; for Schedule 2, it reports 7 at risk and 3 affected. These are counts, not a randomized comparison. The unequal group sizes and non-randomized allocation mean the figures should not be read as showing that one schedule caused more or fewer serious events. Differences in dose, participant characteristics, exposure, or follow-up could matter, and those details are not reported in the registry record.

The listed serious adverse event terms are nausea, vomiting, pneumonia, catheter site infection, and feeding tube complication, each recorded as 14.3%, and abdominal pain, recorded as 4.8%. The record does not specify the denominator or clarify whether subjects could contribute more than one term. The percentages therefore should not be added together or treated as percentages of all enrolled subjects without further information. Deaths are not reported in the group figures.

Serious adverse events are not identical to DLTs. DLTs use the trial’s specific criteria, timing window, exclusions, and attribution rules. The registry record does not report which serious adverse events, if any, met the DLT definition. These figures describe posted serious-event information; they do not establish overall safety, comparative risk, or treatment effect.

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

The record describes a first-in-human Phase I study of oral MSC2015103B in advanced solid tumors, with dose escalation and two treatment schedules. Its primary safety question was whether subjects experienced DLTs through Day 21 of Cycle 1. The definition and safety population are stated, but the primary DLT count is not reported in the registry record. This leaves the central endpoint unanswered in the posted information.

Some serious adverse event counts are reported for each schedule, along with selected terms and percentages. They establish that serious events were recorded in both groups, but do not support a reliable causal comparison. Participants were not randomized, the groups are not like-for-like controls, and relevant details about dose, participant features, exposure, and follow-up are absent from the registry record. The figures also do not indicate which events qualified as DLTs.

The registry’s aims include evaluating tolerability, drug handling, and possible anti-cancer effects. A stated aim is not a result. The record lists pharmacokinetic and other secondary outcomes, but does not report their numerical findings in the registry record for interpretation. It likewise does not report an efficacy result that could establish anti-cancer activity.

These data should not be read as proving that MSC2015103B is safe or unsafe, that one schedule is better than the other, or that the drug is effective or ineffective. They support a limited account of the trial design and the specific adverse event counts posted. Without the primary DLT result, analysis details, and fuller outcome reporting, the precision and completeness of the trial’s safety assessment cannot be judged from the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why early-phase safety studies require careful attention to endpoint definitions and assessment windows. A DLT is not simply any adverse event: the registry specifies qualifying events, exclusions, investigator attribution, and a Cycle 1 period through Day 21. Those rules determine which observations contribute to the primary safety endpoint. Without the resulting count, readers can understand the intended measure but cannot evaluate its observed result.

It also demonstrates the distinction between describing groups and comparing treatments. The registry lists two schedules, but allocation was non-randomized. Counts from these groups can describe events recorded in each group; they cannot isolate a schedule effect from other differences. This distinction is important even when the counts look directly comparable, because design determines what conclusions a contrast can support.

Reporting the denominator alongside affected-subject counts is useful for understanding the scale of observed safety data. Yet denominators do not answer every question: exposure, observation time, event definitions, and completeness of follow-up also affect interpretation. The registry does not report all of these details. Similarly, a list of pharmacokinetic endpoints identifies what investigators intended to measure, but without numerical results it does not describe drug exposure.

The record’s terminated status and its lack of reported inferential analyses further highlight the value of transparent outcome reporting. The reason for termination, the sample-size rationale, and the statistical plan are not reported in the registry record. This limits evaluation of how the study’s original aims relate to the information ultimately posted. The statistical lesson is not that the trial has no value, but that design information and incomplete outcome reporting support narrower conclusions than a fully reported, analyzable dataset would.

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 DLT count, the endpoint named as primary, is not reported in the registry record. Without it, the key safety outcome cannot be quantified or assessed for precision. The record also reports no inferential analyses, so it does not provide a confidence interval or formal comparison for the primary endpoint.

Although enrollment is listed as 28, the registry does not report the number assessed for DLT or explain how incomplete Cycle 1 observation was handled. The safety analysis set includes people who received at least one administration, but that does not establish completeness of follow-up. The trial’s terminated status is recorded, while the reason for termination and its implications for outcome collection are not reported.

The non-randomized schedule groups cannot be treated as equivalent control groups. Dose levels and group-specific participant characteristics, exposure, and follow-up are not reported in the registry record. The serious-event terms have percentages, but their denominators and counting rules are not specified in the registry record recorded. Deaths are not reported in the group figures.

Other important information is absent: the trial-specific sample-size justification, detailed dose-escalation rules, statistical analysis plan, handling of missing data, multiplicity strategy, and numerical results for the listed pharmacokinetic and other secondary outcomes are not reported in the registry record. These limitations restrict both the completeness of the safety interpretation and the ability to distinguish descriptive observations from planned statistical inference.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: MSC2015103B in Solid Tumors — NCT01453387.
• Registry record last updated 2017-05-08; status last verified 2017-03.
• Results first posted 2017-05-08.
• 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

NCT01453387 is a Phase I, first-in-human, non-randomized, unmasked, parallel study of oral MSC2015103B in advanced solid tumors. Enrollment is listed as 28; the study began in 2011-09, reached primary completion in 2013-07, and is listed as terminated. The registry describes two treatment schedules and dose escalation.

The primary outcome was the number of subjects with DLT through Day 21 of Cycle 1, assessed under NCI Common Terminology Criteria for Adverse Events version 4.0. Its result is not reported in the registry record. Serious adverse event counts are posted for both schedule groups, but the non-randomized design does not support a like-for-like causal comparison. Numerical pharmacokinetic results, the termination reason, sample-size rationale, and statistical analysis plan are not reported in the registry record.